Turkish Association for Psychopharmacology

thInternational Congress on PSYCHOPHARMACOLOGY

2nd International Symposium on Child and Adolescent Psychopharmacology

From Neuroscience to Clinical Practice: Tailoring Treatments

April 16th – 20th 2014 Susesi Hotel – ANTALYA / TURKEY

Scientific Program Abstracts

Scientific Program Abstracts



Cognitive behavioral group therapy in obsessive compulsive disorder

Kadir Ozdel

Diskapi Yildirim Beyazit Training and Research Hospital, Department of Psychiatry, Ankara-Turkey e-mail address:

Obsessive-compulsive disorder (OCD), which is characterized by obsessions and compulsions, is usually a chronic, heterogeneous disorder with marked deterioration in social and vocational functioning. According to the World Health Organization, OCD is one of the top causes of illness-related disability worldwide. Although various pharmacological treatments are proposed as effective for the treatment of OCD cognitive behavioral therapy (CBT) represents an elegant option of treatment, either itself or together with pharmacological treatments. Behavioral therapy (BT) which aims behavioral change thorough the exposure and response prevention (ERP) has been using effectively but with partial successful since 1960’s. Partial success that was achieved thorough BT was improved by adopting cognitive techniques and methods as from 70’s. Although research conducted using individual CBT reported response rates up to 83%, as from 2000’s Cognitive behavioral group therapy (CBGT) was proposed an advantageous alternative of treatment with similar effectiveness. However later research suggested that CBT in a group setting could be performed effectively, but that individual CBT was more effective. Nevertheless, it is difficult to know which CBT modality is more effective in the absence of head-to-head comparison. Taking into account above-mentioned consideration, we discuss pros and cons of CBGT for OCD. CBGT can be cost effective in comparison to individual therapy and has unique features like observational learning opportunity. On the other hand, subtle group factors such as lack of group cohesion or dysfunctional interpersonal interactions between the group members can be problematic and toxic to the group therapy process. Although research suggests that individual therapy was more effective for the OCD, to us preliminary preparation might increase the efficacy of CBGT. Keywords: obsessive-compulsive disorder, cognitive therapy, behavioral therapy, psychotherapy, group

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S1


Cognitive behavioral group psychotherapy for depression

Selcuk Aslan

Gazi University, Faculty of Medicine, Department of Psychiatry, Ankara-Turkey e-mail address:

Cognitive behavioral therapy (cbt) in the treatment of depression , effective as well as individual CBT. Best results are obtained with the implementation of group CBT within 12 – 16 weeks of group therapy, consisted of 4-8 people. Therapy conducted with the similar structure and content of individual CBT. Interpersonal factors psychoeducation and motivational factors can contribute positively to the group therapy process. Sessions are started with mood control, feedback on the previous sessions, and checking homework and agenda setting, group sessions is completed in 75 to 90 minutes. After agenda setting, specific cognitive and behavioral techniques studied with the participants during session, giving a psychoeducation on depression, sharing a cbt formulations for depression, identification of emotions and thoughts, recording daily automatic thoughts, revealing beliefs and examination of evidence supported this beliefs, common cognitive distortions are evaluated , then creating alternative beliefs and strategies implemented in ongoing group sessions.

Most of the group session is completed with getting feedback on session and implementing homework. Behavioral interventions includes, detecting events in the past that makes patients feel good , and in session activity planning, pleasure and mastery degree during the event is evaluated and recorded. Procrastination is one of the most negative behavioral strategies that can be worsened depressive symptoms. Motivation and time management strategies are also implemented for coping with procrastination. Defining problems and creating different solutions to solve the problems is another effective way that can be implemented in further group session. In further sessions identifying life problems and teaching problem solving techniques and, cope with possible early signs of depression are studied, and communication skills and empathy exercises and problem solving approaches are applied to specific situations for each member. Keywords: cognitive behavioral group psychotherapy, depression

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S1

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S1

Scientific Program Abstracts


EEE WPA-Servier Academy-new educational model for young researchers

Peter Morozov

Russian National Medical Research University, Moscow-Russia e-mail address:

According to the decision of the 2nd Meeting of the Heads of WPA Zone 10 Psychiatric Societies (October 2012, Kharkov), a database for East European magazines in Russian has been created. It was also decided for an intensive magazine articles exchange within this database. In order to improve the quality of the material and to cover the International Psychiatric Congresses more deeply, the Heads suggested forming a group of young scientific observers. Within the framework of the WPA Educational Program, the East- European Educational WPA-Servier Academy has been established. On basis of references of national Societies 12 young researchers from Russia, Belarus, Ukraine, Georgia, Armenia, Azerbaijan, Kazakhstan, with equally good knowledge of Russian and English have been selected. During the years 2013-2014, this group shall be attending/attended major European Congresses (EPA and ECNP) and making reviews on the most interesting matters discussed at Congresses. After the reviews are edited by the supervisors, they will be added into the database and granted for publishing in various WPA Zone 10 magazines without limitation. This idea was for the first time put into practice at the EPA Congress in Nice, the first 11 reviews were forwarded for publication to the Presidents of Societies at the 3rd meeting (June 2013, Almaty). 15 reviews have been published already in psychiatric magazines of Russia, Belarus, Ukraine and Azerbaijan.

The next set of reviews were prepared by the members of EEE WPA-Servier Academy after the ECNP Congress in Barcelona and forwarded for publication in December 2013.

This approach definitely enhances scientific outlook of young researchers and is developing new skills in reports preparation. Distribution of such scientific information among psychiatrists of Post-Soviet countries on regular basis shall contribute to development of WPA Educational Program on our continent and raise the professionalism of specialists.

Keywords: educational model, researchers

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S2


Oligodendrocyte dysfunction in schizophrenia: mechanism and target of treatment

Xin Min Li

University of Alberta, Department of Psychiatry, Alberta-USA e-mail address:

Schizophrenia is characterized by disturbances of perception, emotion, social functioning and cognition. Studies suggest that genetics, early environment, neurobiology, psychological and social processes are important contributing factors. Increasing evidence supports an important role of Oligodendrocyte (OL) in the pathogenesis of schizophrenia. Genome-wide gene expression analyses clearly have shown dysregulation of myelination-related genes. Neuropathological and neuroimaging studies demonstrated loss of oligodendrocytes and myelin abnormalities in the brains of schizophrenic patients. Furthermore, patients with various demyelination disorders have psychotic symptoms, indicating a correlation between demyelination and schizophrenia. The OL dysfunction hypothesis, however, has never been experimentally tested due to the lack of suitable animal models. We have revisited the cuprizone (CUP)-induced demyelination model, and found that a low dose (0.2%) of CUP caused OL dysfunction and demyelination primarily in the prefrontal cortex and the corpus callosum in C57BL/6J mice. Our data has found that the OL dysfunction, degeneration, and demyelination in this model were accompanied by the development of schizophrenia-like behaviors, and that enhancing remyelination by promoting OL proliferation and maturation significantly improved these behavioral changes.

Keywords: oligodendrocyte dysfunction, schizophrenia, treatment Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S2

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Scientific Program Abstracts


Reactive aldehydes: what is their role in neuropsychiatric disorders?

Glen B. Baker, Erin M. MacKenzie, Dmitriy Matveychuk

Neurochemical Research Unit, Department of Psychiatry, University of Alberta Edmonton, AB-Canada e-mail address:

The management of neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS), is one of the leading healthcare challenges in the fields of neurology and psychiatry. Although the aforementioned disorders appear to have different mechanisms of pathogenesis, they share a common finding of increased production of toxic reactive aldehydes in the central nervous system. These aldehydes, including acrolein, 4-hydroxy-2-nonenal, malondialdehyde, methylglyoxal, formaldehyde and 3-aminopropanal, are produced by a variety of endogenous sources including: membrane lipid peroxidation by reactive oxygen species; metabolism of monoamines and polyamines; and catalytic activity of primary amine oxidase. Reactive aldehydes can readily form adducts with nucleophilic groups in amino acids, nucleic acids and aminophospholipids, resulting in disruption of protein and cell membrane function, inhibition of DNA, RNA and protein synthesis and interference with mitochondrial pathways. There have been reports of increased aldehyde content in the cerebrospinal fluid of AD, PD and MS patients. Investigators have also reported increased aldehyde adducts in the hippocampus and adducts co-localized with neurofibrillary tangles in AD patient brains. Several in vitro studies have demonstrated that reactive aldehydes can promote formation of β-amyloid oligomers and protofibrils and induce tau phosphorylation, the major pathological hallmarks of AD. Primary amine oxidase, the enzyme responsible for production of methylglyoxal and formaldehyde, has been shown to be over-expressed and co-localized with β-amyloid deposits in cerebral blood vessels of AD patients. In PD, there are reports of increased aldehyde content and aldehyde-modified α-synuclein in the substantia nigra of patients. Interestingly, increased aldehyde content was found in the hippocampus and substantia nigra of patients exhibiting pre-clinical AD and PD pathology, respectively, suggesting that reactive aldehyde production may be an early event in the progression of these disorders. In MS patients, it was discovered that increased aldehyde content was present in oligodendrocyte-like cells in active lesions of patients. One promising strategy in treatment of these neuropsychiatric disorders is the reduction of reactive aldehyde levels in the central nervous system. Trials with antioxidant therapy have produced largely conflicting results in AD in PD, although several further investigations are now underway. While antioxidants should reduce the rate of lipid peroxidation, there are multiple additional souces of endogenous reactive aldehyde generation. Another approach may include directly sequestering the aldehydes with drugs containing nucleophilic functional groups. The sequestration of acrolein with the hydrazine drug hydralazine has been shown to be beneficial in an animal model of MS, however, these studies have not been carried out in the clinical population. We have investigated the actions of the antidepressant hydrazine drug, phenelzine and its active metabolite β-phenylethylidenehydrazine (PEH) and found that both compounds sequester the reactive aldehydes mentioned above and reduce the formation of formaldehyde from methylamine by inhibiting primary amine oxidase. The possible clinical implications of these actions of these drugs will be described.

The authors are grateful to the Canadian Institutes of Health Research, the University of Alberta, the Canada Foundation for Innovation and the Queen Elizabeth II Graduate Studentship program for financial support.

Keywords: reactive aldehydes, neuropsychiatric disorders

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S2-S3


Mild depression and normal sadness: Language diagnostic criteria

Daria Smirnova1, Dmitry Romanov1, Elena Sloeva2, Natalia Kuvshinova2, Alexandr Krasnov2, Gennadii Nosachev1

1Samara State Medical University, Psychiatry, Narcology, Psychotherapy and Clinical Psychology Department, Samara-Russia 2Samara State Medical University, Pedagogics, Psychology and Psycholinguistics Department, Samara-Russia

e-mail address:

Objective: High rates of depression are viewed with some degree of skepticism due to the issue of validity and reliability of psychiatric diagnoses. The difficulties in the diagnostic differentiation of ordinary sadness and depression in the continuum of depressive states, and the existence of false-positive diagnoses of depression are identified. Incorrect diagnostics of mild depressions is related to clinical

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Scientific Program Abstracts

interpretation of thinking content and structure within the depressive triad. Whereas nonverbal (motor) and affective components are similar to variations of normal sadness in healthy individuals, associative component reveals the most sensitive psychopathological unit, which is represented in language changes.

Methods: The study sample of 124 patients aged 41.85±11.89 years (67% female) was taken from Russian native speakers diagnosed with mild depression (D) in primary care and consulted at the University Psychiatry Department. 77 healthy persons (65% female) (H), including 35 healthy persons with reactions of normal sadness (NS), were observed as controls. Speech was studied using a number of standard psycholinguistic procedures at the superficial and deep levels of language. Statistical data analysis included descriptive methodics, nonparametric analysis (U-criteria Mann-Whitney, test by Wald-Wolfowitz, p<0,05), mathematic modeling of discriminate analysis (λ–Wilks; method Standard).

Results: Lexical-stylistic sublevel of speech in D was characterized by verbosity (D-311.18±11.43 words in text; H-197.25±11.24), inversive word order (D-124(100%);H-5(6.49%)), narration (D-106(85.48%);H-56(72.73%)) dominated over reasoning (D-18 (14.52%);H- 21(27.27%)), communicative discourse signs (P-124(100%);H-9(11.69%)), increased number of phraseologisms (P-3.74;H-1.21), tautologies (P-3.77;H-1.44), repetitions (P-4.42;H-1.82), inversions (P-4.00;H-1.08), ellipsis (P-3.73;H-1.60). Lexical-grammar sublevel contained more pronouns of all types with the prevalence of personal (P-124(100%);H-54(70.13%) pronouns, continuous form verbs (P-116(93.55%);H-26 (33.77%)) in past tense (P-124(100%);H-2(2.6%)). Syntaxical-stylistic sublevel represented the prevalence of simple (P-99(79.84%);H-2(2.6%)) sentences, truncated and impersonal (P-84(67.74%);H-7(9,.09%)) types.

Component analysis of patients’ speech demonstrated the distortion of quality and reduction of semantic component (over evaluated existential and family categories, diminished cognitive and altruistic categories, overestimation of communicative and hedonic categories over the self-realization and social status).

In accordance to clinical criteria, the sample of mild depression was subdivided onto subtypes (anxious, asthenic-hypodynamic, melancholic) where appropriate language differences were also revealed.

Speech in NS, in comparison to H, was impoverished by ellipsis (NS-1.60, H-1.21), tautologies (NS-1.66,H-1.22) and lexical, semantic repetitions (NS-1.97,H-1.69). Tempo of speech was reduced due to defaults (NS-1.71,H-1.38). Persons used preferentially verbs in continuous form (NS-54.29%,H-16.67%) in present tense (NS-88.57%,H-47.62%).

Mathematical modeling proved the hypothesis about importance of language criteria and significance of verbal markers for diagnostics and differentiation of mild depression and normal sadness (98%, λ–Wilks=0.0007;p<0.001).

Conclusions: 1) Mild depression and state of normal sadness are characterized by definite psycholinguistic features, which reflect cognitive dysfunction and thought strategies significantly related to the symptoms of leading hypothymic affect and signs of mood deviation. 2) In mild depression and state of normal sadness, the speech is distorted both in structure and in semantics. 3) The structure of affective component significantly determines the whole mental status and is represented in speech, so the sensitivity of linguistic markers in diagnostics of mild depression and normal sadness is revealed.

Keywords: language, mild depression, diagnosis, psycholinguistics Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S3-S4


Antidepressants and their effects on oxidative stress

Kadir Karakus

Isparta State Hospital, Isparta-Turkey e-mail address:

Major depressive disorder is a common mental disorder. Increasing evidences suggests that major depression is associated with increased oxidative stress and lipid peroxidation. Many studies indicate that, reactive oxygen species induce neuronal damage and they have an important role in the pathophysiology of depression. Oxidative stress is defined as the imbalance between production of reactive oxygen species (superoxide radical, hydrogen peroxide and hydroxyl radical) and reactive nitrogen species (peroxynitrite, ONOO-) and their insufficient decomposition by the antioxidative defense system. In normal physiological conditions, reactive oxygen species and reactive nitrogen species are produced continuously and they are effectively controlled or eliminated by intracellular and extracellular antioxidant defense systems. This antioxidative defense systems involves enzymatic antioxidants; superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and paraoxonase and nonenzymatic antioxidants; reduced glutathione, provitamin A, vitamin C and E, coenzyme Q10, carotenoids and trace elements like copper, zinc or selenium. High oxygen consumption, high amount of polyunsaturated fatty acids and iron and low activities of antioxidant enzymes makes sensitive brain to oxidative damage. In high

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concentrations, reactive oxygen species lead to damage of components of the cell, including proteins, lipids and DNA. Antidepressants are widely used in the treatment of major depression and other psychiatric disorders and their use are increasing with each passing day. The exact mechanisms of action of antidepressants are unknown but they may act by suppressing production of several proinflammatory cytokines and reactive oxygen species, reactive nitrogen species or enhancing antioxidant defense systems such as antioxidant enzymes. In vitro studies were conducted to investigate the antidepressants effects on antioxidant and oxidant system. These studies revealed antioxidant related effects and their protective effects against oxidative stress for antidepressant drugs. Moreover, it has been suggested that, some antidepressants may be pro-oxidant at high doses in in vitro studies. In animal studies, different animal models were used to investigate the oxidant and antioxidant effects of antidepressant drugs. Most of animal studies suggested that antidepressant drugs decrease oxidative stress and modulate the antioxidant enzyme activities. In recent years, an increasing number of studies have focused on the potential effects of antidepressant treatments on oxidative stress and antioxidant status in humans. Most of human studies have shown that, antidepressant drugs have antioxidant properties and they reduce increased oxidative stress, when they are used to treat the patients, in consistency with the findings of in vitro and animal studies. Also in some studies, antidepressants did not modify any oxidative and antioxidative parameters or induced oxidative stress in patients. Therefore, to elucidate the effects of antidepressants on oxidative and nitrosative stress we need the well-designed studies. In addition, it has been shown that some of the classic antioxidants causes antidepressant like effects and these are indicates us new targets for antidepressant treatment.

Keywords: antidepressants, oxidative stress, depression

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S4-S5


Effects of antipsychotic drugs on oxidative stress

Kadir Demirci

Suleyman Demirel University, Isparta-Turkey e-mail address:

Schizophrenia is a severe chronic debilitating psychiatric disease that affects almost 1% of the world’s population. Etiology of schizophrenia is still not completely understood. There has been an increasing number of studies which indicate that reactive oxygen species may play a crucial role in the pathogenesis of schizophrenia, genetic factors aside. Tardive dyskinesia and extrapyramidal side effects are frequently observed side effects of treatment with especially older generation (typical) antipsychotic drugs. It is suggested that oxidative stress may responsible for etiology of tardive dyskinesia that may develop after antipsychotic treatment. The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment.

Oxidative stress is a common term, which generally used to describe the unbalanced situation between oxidants and antioxidants, in favor of oxidants. Under physiological conditions, reactive oxygen species can be produced. If the excess amount of reactive oxygen species cannot be detoxified by antioxidant defense mechanism, cellular damage would be occurs (lipid peroxidation, DNA damage etc.). The controversial data was also reported in the literature on oxidative stress markers in schizophrenia patients. Abnormalities in the antioxidant defense system and a major decrease in antioxidant levels were determined in schizophrenic patients. Several studies have shown differences for the activities of antioxidant enzymes. Antipsychotic drugs are widely used in treating schizophrenia. Since the relationship between schizophrenia and oxidative stress showed, many studies have been performed about the possible protective effects of antipsychotic drugs on oxidant/antioxidant system and lipid peroxidation. The effects of antipsychotic drugs on oxidant, antioxidants and lipid peroxidation have become a subject of curiosity. It has also been suggested that some older generation antipsychotics may have shown pro-oxidant effects by increasing the cellular damage, especially in brain. Some antipsychotic drugs were reported to have neuroprotective effects against oxidative stress at the cellular level. This panel aims to provide information about the effects of antipsychotic drugs on oxidative stress.

Keywords: antipsychotic drugs, oxidative stress

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S5

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S5

Scientific Program Abstracts


Translational studies on the effects of lithium

Nicol Ferrier

Newcastle University, Institute of Neuroscience, Academic Psychiatry, UK e-mail address:

In preclinical experiments, lithium has a myriad of actions. A brief review of the main actions of lithium will be given concentrating on its effects on monoamines, on signal transduction pathways and on neuroplasticity. It is not clear which of these many actions are important for lithium’s unique clinical profile. One way around this problem is to do studies of lithium in normal human subjects to investigate which cellular effects of lithium appear to have significant effects in the human subject. An example of such a study is given below. However, it should be noted that this technique might not provide all the answers since it is conceivable that lithium’s important clinical effects are only evident, when it is given to people who are unwell with disturbed physiology.

A recent randomized placebo controlled study of lithium involving 24 healthy men will be described. There is preclinical evidence from our group and others that one of the important actions of lithium is to attenuate the release of dopamine without change in postsynaptic dopamine receptors and it is being proposed that the anti-manic properties of lithium derive from this effect. In our study, mania was modeled by the administration of methylphetamine. Sustained attention, known to be disturbed in mania, was assessed during functional magnetic resonance imaging. Within the lithium group, response times were slowed and the effects of methylphetamine on functional magnetic resonance imaging contrast diminished suggesting that lithium is associated with reduced dopamine release in humans. Further examples of the translational approach will also be reviewed. A series of studies have investigated the putative neuroplastic effects of lithium. Changes in neuroplasticity markers have been seen in rat studies of lithium but the equivalent human studies are negative. There is uncertainty over the effect of lithium on grey matter volumes in MRI scans in controls and in bipolar disorder and this evidence will be discussed. Finally, studies examining the biochemical and neuroendocrine effects of lithium in normal controls will be reviewed and contrasted with data from animal studies and studies of bipolar disorder. All these findings will be discussed in the context of current theories of lithium’s mechanism(s) of clinical action.

Keywords: translational studies, lithium

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S6


Why the rational use of medicines is important?

Ahmet Akici

Marmara University, Faculty of Medicine, Department of Medical Pharmacology, Istanbul-Turkey e-mail address:

Medicine is one of the basic health care products needed for protecting, promoting the health and wellbeing, etc. For a sustainable health care service, it is mandatory to use medicines with regard to rational principles. World Health Organization (WHO), defined rational use of medicines (RUM) as “Patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community.” Since its definition, over the past 30 years many activities have been conducted for promoting RUM. Despite these activities, irrational use of medicines (IUM) still continues to be one of the significant public health problems.

In time, particularly in recent years, the number, the variety and the use of medicines has dramatically increased. This increase has brought some affirmative improvements (i.e. new medication opportunities) as well as some important health care problems (i.e. treatment failures, drug resistance, health care problems related to medication error, drug interactions, increased health care costs). Furthermore, the knowledge which physicians, patients and other people involved in the drug utilization process need to know increases day by day, in parallel with the increase in the knowledge about treatments and medicines. This situation brings along the lack of knowledge and information pollution. These problems, which are characterized as IUM, are the major health care problems in countries. All health care professionals, particularly physicians assume primary responsibility for these problems. What extent the health care professionals move away from the RUM principles in their field, they become the source of problems. Therefore, it’s needed to conduct training and informing

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activities particularly for physicians who are the key people for the solution as well as other health care professionals. Psychopharmacology is a special area, which specific developments encountered and RUM principles had to be put in practice in all levels. In this congress, it’s believed that this RUM subjected panel will contribute to the need for the information exchange. As stated above, in this panel the importance and the subject of RUM will be discussed in detail.

Keywords: rational drug use, treatment, psychopharmacology

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Scientific Program Abstracts



Childhood trauma and dissociation in patients with bipolar disorder

Atilla Tekin

Sisli Etfal Training and Research Hospital, Istanbul-Turkey e-mail address:

Traumatic experiences during childhood are frequently emphasized in the etiology of bipolar disorder as well as many other psychiatric disorders. In bipolar patients with a history of childhood trauma, studies have shown that the age of disease onset age is earlier, the number of affective episodes is higher, the rate of rapid cycling is increased and psychotic symptoms as well as suicide attempts are more common. Dissociation, which is characterized with changes in or deterioration of the normal integrative functions of memory, identity and consciousness, manifests in many psychiatric disorders. Some studies have demonstrated dissociative symptoms to be present in psychotic disorders such as schizophrenia, anxiety disorders and in borderline personality disorders and that, there is a relationship between childhood traumatic experiences and dissociative symptoms. Additionally, there are fewer studies and case reports in literature investigating the relationship between bipolar disorder and dissociation. These researches have shown that in bipolar disorder patients with high dissociation scores, the onset of the disease may be earlier and treatment responses may be lower.

Keywords: childhood trauma, dissociation, bipolar disorder Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S8


Bipolar disorder comorbidity with dissociative and conversion disorders

Bahadir Bakim

Canakkale Onsekiz Mart University, Faculty of Medicine, Department of Psychiatry, Canakkale-Turkey e-mail address:

The prevalence of bipolar disorder (BD) was determined to be 0.4-1.1%. However, the lifetime prevalence estimates of bipolar spectrum disorder are now placed at least 5% of the general population. Psychiatric comorbidities are common in the patients with BD. Some authors report the incidence rates of lifetime comorbidity in BD as high as 70%. Bipolar patients with a history of childhood trauma have an earlier age of onset, have more affective and rapid cycling episodes, have more psychotic symptoms and suicide attempts. Latalova et al found that bipolar patients had higher DES scores compared to healthy volunteers.

Although comorbidities are common in DD, cases in which BD is comorbid with DD is generally overlooked because dissociative symptoms obscure and impair the individual’s self-perception and self-report.

In a study by Jans et al, affective disorder co-morbidity is found 71% among adult patients with dissociative disorders.

Foote et al found that a dissociative disorder diagnosis was more strongly associated with suicidality or self-harm than any other diagnosis. Studies show that 1 to 2.1% of patients with DID had completed suicide, with an incidence of 61 to 72%, who have attempted suicide. Studies conducted in patients with the most complex dissociative disorder, dissociative identity disorder (DID), have found between 34%and 86%have histories of self-mutilation. Patients with DD have been reported to have used more methods of self-injury and started to injure themselves at an earlier age than patients who have not dissociated.

Conflict with others and difficulty with boundaries as well as frequent re-victimization in subsequent relationships are all too common. Emotional dysregulation occurs frequently in this subset and may be the precipitant of psychiatric treatment.

There is evidence that patients with DD may drop out of cognitive behavioral treatments, indicating that programs that do not specifically address dissociation may not be well tolerated.

Atypical antipsychotic drugs that block both D2 and 5-HT2A receptors may be of use in treating complex trauma cases with “psychotic features” although auditory hallucinations and voice hearing in subjects with trauma disorders could be conceptualized as dissociative rather than psychotic in some cases.

Most medications (e.g., antidepressants, anxiolytics) are prescribed for comorbid anxiety and mood symptoms, but these medications do not specifically treat the dissociation. Presently, no pharmacological treatment has been found to reduce dissociation. Although

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antidepressant and anxiolytic medications are useful in the reduction of depression and anxiety and in the stabilization of mood, the psychiatrist must be cautious in using benzodiazepines to reduce anxiety as they can also exacerbate dissociation. In treating patients with DID, there are reports of some success with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, monoamine oxidase inhibitors, beta blockers, clonidine, anticonvulsants, and benzodiazepines in reducing intrusive symptoms, hyperarousal, anxiety, and mood instability. Other possible suggestions for pharmacological interventions for DID include the use of prazosin in reducing nightmares, carbamazepine to reduce aggression, and naltrexone for amelioration of recurrent self-injurious behaviors.

Keywords: dissociative disorders, bipolar disorder, comorbidity, treatment. Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S8-S9


Conversion disorder, dissociation, comorbidity

Sinan Yayla

Kastamonu State Hospital, Kastamonu-Turkey

e-mail address:,

Conversion disorder (CD) is defined as the emergence and course of one or more symptoms, which are caused by psychological conflicts or needs affecting the voluntary motor or perceptual functions. Although CD can be seen at any time between early childhood to late old ages, it is reported to be most common between the 15-35 years of age. In a general hospital setting 5 to 16% of all psychiatric patients have conversion symptoms. In Turkey, among outpatients who were admitted to a primary health care center, the lifetime prevalence of conversion symptoms was 48.2%. In western societies, the rate of CD is 1-3% in clinical populations whereas in non western societies rate for CD is about 10%. CD is more prevalent among females compared to males with a ratio ranging between 2:1 to10:1. CD is also more prevalent in rural areas, developing countries, low socioeconomic classes, among under educated people and those with relatively low medical knowledge.

Conversion disorder is generally accompanied by a neurological or psychiatric disorder. Comorbidities significantly affect the prognosis and the treatment of CD symptoms. The most common psychiatric comorbidities for CD are mood disorders, anxiety disorders, dissociative disorders and somatoform disorders. Personality disorders also accompany CD. The comorbidity of dissociative disorders interferes with the treatment of primary disorder further complicating the prognosis.

Keywords: conversion, dissociation, comorbidity

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S9


Dissociative disorders in DSM-5

Serhat Citak

Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul-Turkey e-mail address:

The DSM and ICD formulations originate in Janet’s conceptualization of dissociation, which he termed ‘‘de ́sagre ́gation mentale’’. Janet postulated that a failure of integration of mental elements was the fundamental aspect of hysterical (i.e. dissociative and conversion) disorders.

In DSM-5, possession experiences are included in the diagnostic criteria of dissociative identity disorder (DID) as well as in related types of other specified dissociative disorders possibly, non-dissociative psychiatric disorders with an onset in adulthood compensate Downloaded by this difference by possession experiences accompanying the primary disorder. Dissociative subtypes of schizophrenia, depression, and PTSD may be among them Experiences of possession seem to be a common final pathway of adaptation to traumatic stress in the spectrum extending from normality to pathological. Last but not least, future studies may lead to development of revised diagnostic criteria (e.g. requirements for a minimum of severity and chronicity) for adolescent DID and allied dissociative disorders in

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updated versions of the DSM-5 to exclude dissociative phenomena possibly normative or rather acute or transient for this age group. DSM-IV-TR portrays DID by means of two dissociative phenomena: amnesia and the presence of alter personalities. DSM-IV-TR also notes that DID patients may manifest flashbacks, voices, and conversion symptoms. Dell proposed a revised concept of DID that he called “major dissociative disorder.” He organized the previously replicated findings about DID into three diagnostic criteria: a) pervasive dissociation (i.e., memory problems, depersonalization, derealization, flashbacks, somatoform dissociation, and trance); b) partially dissociated manifestations of an alter personality (i.e., child voices; internal struggle; persecutory voices; partially dissociated speech, thoughts, emotions, impulses, and actions; temporarily dissociated knowledge/skills; disconcerting experiences of self-alteration; and self-puzzlement); and c) fully dissociated manifestations of an alter personality (i.e., time loss, “coming to,” fugues, being told of forgotten behavior, finding unexplainable objects among one’s possessions, and finding evidence of one’s previous unknown actions).Research on DID has repeatedly reported that DID patients manifest memory problems; depersonalization; derealization; identity confusion; trance; ego-alien, passive influence experiences such as the Schneiderian first-rank symptoms of “made” feelings, “made” impulses, “made” actions, influences playing on the body, thought insertion, and thought withdrawal; child voices; persecutory voices; voices commenting; voices arguing or conversing; somatoform/ conversion symptoms; time loss; fugues; finding evidence of one’s previously unknown actions; and flashbacks.

Spiegel et al. made the following recommendations for DSM-5: 1.Depersonalization Disorder (DPD) should derealization symptoms as well. 2. Dissociative Fugue should become a subtype of Dissociative Amnesia (DA). 3. The diagnostic criteria for DID should be changed to emphasize the disruptive nature of the dissociation and amnesia for everyday as well as traumatic events. The experience of possession should be included in the definition of identity disruption. 4. Dissociative Trance Disorder should be included in the Unspecified Dissociative Disorder (UDD) category.

Keywords: dissociative disorders, DSM-5, phenomenology

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S9-S10


A comparison of psychotic symptoms in schizophrenia and dissociative disorders

Ishak Saygili

Erenkoy Mental Health and Neurology Training and Research Hospital Istanbul-Turkey e-mail address:

The nature of some symptoms are very complicated and most of the time it is hard to determine whether these symptoms are dissociative or psychotic. The psychotic symptoms, which were described by Diagnostic Statistical Manual (DSM) may be seen also in dissociative disorders. In a study dissociative identity disorder (DID) patients had higher positive symptoms scores on the positive and negative symptoms scale (PANSS) compared to schizophrenia. There are evidences that childhood traumas (CTs), especially physical and sexual abuse are increasing the dissociative and psychotic symptoms which seen in schizophrenic patients. CTs are also a well-known, common etiologic factor for dissociative disorders. Hallucinations are one of the most common psychotic symptoms in schizophrenia and dissociative disorder. Phenomenological and cognitive differences of hallucinations in dissociative disorders and schizophrenia are still not clearly putted forth. There were different criteria’s accepted for specifying, which types of hallucinations should be the focus of clinicians effort. There have been some phenomenological specialties offered for distinguishing them properly. Metacognitive beliefs, thought suppression, belief about hallucinations are concepts, which have shown associated with hallucinations. Similarly, insight and its cognitive components are studied in schizophrenia and those studies revealed its associations with hallucinations. This debate has aimed to review the phenomenological features of psychotic symptoms which seen both in schizophrenia and dissociative disorders, and has focused on a hypothetic cognitive model, which has been suggested for auditory hallucinations.

Keywords: childhood trauma, dissociative disorders, metacognition, psychotic symptoms, schizophrenia Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S10

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Executive functions in children and adolescents with attention deficit hyperactivity disorder

Yasemin Yulaf

Tekirdag Children and Adolescents Mental Health Clinic, Tekirdag-Turkey e-mail address:

ADHD is now increasingly recognized as developmental impairment of executive functions (EFs), the brain’s cognitive management system. Executive function (EF) is a set of self-regulatory mechanisms for planning, organizing, directing, and managing cognitive processes and emotional responses.

Children with ADHD have serious difficulties with EF in so many areas that some psychiatrists and psychologists have proposed renaming this disorder as EF disorder or EF deficit disorder. Many of the executive dysfunctions described earlier are found in children with ADHD including difficulties with priority and time management, planning and organization, initiating and completing tasks in a timely manner, difficulty shifting cognitive set, a high level of procrastination, forgetfulness and poor working memory.

Barkley proposed the hypothesis that attention-deficit/ hyperactivity disorder (ADHD) symptoms may be due to EF deficits. In a meta-analysis of 83 studies, children and adolescents with ADHD exhibited significant deficits compared to those without ADHD in neuropsychological measures of EF; the EF domains that showed impairments included planning, spatial and verbal working memory, response inhibition, and vigilance.

The ES is mediated by various networks in the frontal, parietal and occipital cortices, the thalamus and the cerebellum. It is linked through a series of circuits connecting every region of the central nervous system. The circuits originate in the dorsolateral prefrontal cortex (PFC) / orbitofrontal cortex (OFC), project through the striatum, synapse at the level of the globus pallidus, substantia nigra and the thalamus and finally return to the PFC forming closed loops. Each circuit regulates specific functions. The circuit that is most responsible for coordinating EF is located primarily in the frontal lobe. Functional imaging studies have implicated the PFC as the primary site of cortical activation during tasks involving EF.

There is not yet full agreement regarding exactly which functions should be classified as EFs. But there is a general agreement that there were three core EFs: 1) inhibition [inhibitory control, including self-control (behavioral inhibition) and interference control (selective attention and cognitive inhibition)], 2) working memory (WM), and 3) cognitive flexibility (also called set shifting, mental flexibility, or mental set shifting and closely linked to creativity). From these, higher order EFs are built such as reasoning, problem solving, and planning.

The therapeutic effect of the stimulants in ADHD is associated with their effects on the catecholamine system. Impaired neurotransmission causing executive dysfunction occurs because of abnormalities of the dopamine transporter. All currently approved pharmacotherapies for ADHD, both stimulants and non-stimulants, work by potentiating neurotransmission in the PFC. In ADHD subjects, single doses of the non-stimulant atomoxetine produced selective effects on response inhibition in the absence of effects on attention and memory. Although a norepinephrine reuptake inhibitor, atomoxetine acts primarily via presynaptic norepinephrine transporter blockade and elevates dopamine in selective cerebral regions.

Keywords: working memory, attention deficit hyperactivity disorder Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S11


Therapeutic approaches to anxiety disorders comorbid to ASD

Betul Mazlum

Istanbul University, Institute of Health Sciences, Department of Neuroscience, Istanbul-Turkey e-mail address:

Autism spectrum disorders (ASD) are characterized by social communication difficulties and repetitive, stereotyped behavior. Comorbid features exist in children and adolescents with ASD in addition to the core symptoms and it is known that these patients are at increased risk for anxiety and anxiety disorders. 40% of children with ASD fulfill diagnostic criteria for an anxiety disorder which specific phobia, obsessive compulsive disorder and social anxiety disorder are suggested to be the most frequent ones. There is still disagreement over

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whether anxiety symptoms in ASD are related with core ASD aspects or they just constitute comorbid conditions. In addition, recognition and measurement of anxiety in children with ASD is another problem since low intellectual functioning, which is highly associated with ASD, restricts evaluation of these patients and might lead to underdiagnosis of comorbid conditions. Anxiety associated with ASD contributes to overall impairment in these patients and psychosocial and pharmacological treatment approaches are considered to improve the life quality of both patients and their parents. Although there are treatment options for anxiety disorders in typically developing children, treatment strategies for children with ASD are mostly the adaptation of these options. Antidepressants and antipsychotics are suggested to be effective to treat anxiety in ASD. Furthermore, cognitive-behavioral therapy appears as an effective treatment option for co-occurring anxiety in older and high-functioning children with ASD. We need more double blind controlled studies to test the efficiency of these psychopharmacological and psychosocial treatment options in ASD group. This part of the panel will focus on literature regarding therapeutic approaches to anxiety disorders prevalent in ASD.

Keywords: anxiety, autism spectrum disorders, treatment

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S11-S2


Therapeutic approaches to attention deficit hyperactivity disorder comorbid with autism spectrum disorders

Ayse Kilincaslan

Istanbul University, Istanbul Faculty of Medicine, Department of Child and Adolescent Psychiatry, Istanbul- Turkey e-mail address:

Many individuals with Autism Spectrum Disorders (ADS) exhibit behaviors and symptoms associated with Attention Deficit Hyperactivity Disorder (ADHD). Comorbidity of ADHD symptoms in individuals with ASD have generally been reported to be between 30 and 50% although even higher rates (e.g., as high as 78%) have been reported in clinical samples.

Individuals with co-occurring ASD and ADHD are more severely impaired than those with no ADHD. They exhibit significant deficits in social processing, adaptive functioning, executive control and motor problems, which cause major challenges with educational achievement, socialization and behavioral management in these children. ADHD symptoms are similar whether occurring alone or comorbid with autism, so children with ASD may benefit from the same systematically tested, evidence-based treatments that have been proven successful in typically developing children with ADHD.

Studies have demonstrated the efficacy of methylphenidate treatment of ADHD symptoms in children with ASD, however, the response rates were lower and discontinuation due to adverse effects were higher compared with the non-ASD ADHD population. Two additional medications (i.e., clonidine and atomoxetine) have also reported to be effective in randomized placebo-controlled trials. Atypical antipsychotic agents have been demonstrated to reduce ADHD symptoms in children with ASD, who have co-occurring irritability and agitation. Compared with typically developing children with ADHD, children who have ASD, as in other developmental disabilities seem to have lower effect sizes with these medications and are more sensitive to side effects, including emotionality and agitation.

In this presentation, recent studies on treatment of children with ASD comorbid with ADHD will be presented together with our clinical and research experience.

Keywords: treatment, attention-deficit/hyperactivity disorder, comorbidity, autism spectrum disorders

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S12

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Pharmacotherapy choices for irritability in children and adolescents with Autism Spectrum Disorders

Ozden S. Uneri

Ankara Pediatric and Pediatric Hematology Oncology Training and Research Hospital, Child and Adolescent Psychiatry Outpatient Clinic, Ankara-Turkey e-mail address:

Autism spectrum disorders (ASD) are a class of neurodevelopmental disorders, which affect 1 out of 110 children. Children and adolescents diagnosed with ASD often suffer from severe irritability, including aggression, self-injurious behavior, and tantrums (about 68% of patients). Managing irritability with an effective and safer agent can improve overall functioning in individuals with autism and alleviate burdens on the individual and family. Research into the pharmacotherapy of severe behavioral disturbance in ASD has primarily focused on the atypical antipsychotics. The Food and Drug Administration (FDA) approved risperidone and aripiprazole for the treatment of irritability associated with ASD. Risperidone was approved by FDA in 2006 for the children and adolescents of age 5 to 16, with a maximum recommended dose of 3 mg/d. Aripiprazole was approved by FDA in 2009 for the patients of age 6 to 17. The usual recommended clinical dose for maintenance is between 5 and 15 mg/d. Clozapine, olanzapine, quetiapine, ziprasidone, paliperidone are other atypical antipsychotics which are used for irritability in children and adolescents with ASD. Relatively small sized controlled studies of the anticonvulsants and mood stabilizers (lithium, divalproex sodium, lamotrigine, levetiracetam) for irritability in youth with ASD have generally demonstrated negative results. Alpha2 adrenergic agonists such as guanfacine may be useful for milder irritability symptoms in ASD. One recent study investigated use of the glutamatergic modulator and antioxidant N-acetylcysteine (NAC) for irritability in ASD. In this double blind, placebo-controlled trial, subjects in the NAC group, compared to the placebo group, demonstrated significant improvement in irritability as measured. Additional research is needed to understand the potential role of alpha2 adrenergic agonists and NAC better, as in the treatment of irritability in ASD. Keywords: ASD, irritability, treatment

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S13


Therapeutic approaches to mood disorders comorbid to ASD

Canan Tanidir

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Department of Child and Adolescent Psychiatry, Istanbul-Turkey e-mail address:

Objectives: High rates of aggressive behaviors and severe mood disturbances are documented in children with autism spectrum disorders (ASD) and limited literature documented the presence of bipolar disorder (BPD) comorbidity in ASD populations. Also there is a high incidence of bipolar disorder (BPD) in family members of children with ASD. There is a small number of randomized controlled trials about the treatment protocol of BPD in youth with ASD and the comorbidity rates between these two disorders and there is no treatment guideline for autistic children with bipolar disorder. But this presentation aimed to make a summary of the current consensus on pharmacological treatment options and to briefly review the evidence-based pharmacological agents.

Method: Original articles, reviews and guidelines about the treatment of bipolar disorders and autism in children and adolescents were searched on Pubmed. Key words of “autism, bipolar disorder, mood disorder, pervasive developmental disorders, Asperger syndrome, irritability, mood dysregulation” were used while searching on Pubmed.

Results: Limited literature on the treatment of comorbid BPD in children with ASD suggests that first generation antipsychotics (haloperidol, chlorpromazine, thioridazine) and traditional mood stabilizers (lithium, carbamazepine) are minimally effective for the treatment of mania. On the contrary, in a recent secondary analysis of acute atypical antipsychotic monotherapy trials in BPD youth, acceptable tolerability and robust antimanic response to atypical antipsychotics in the presence of ASD comorbidity was reported. Atypical antipsychotics especially risperidone and aripiprazole seem to be first choice in the treatment of manic or mixed episodes in youth with ASD. The combination of fluoxetine or citalopram with atypical antipsychotics or mood stabilizers seems to be good choice for the acute phase of bipolar depression in youth with ASD.

Conclusion: The actual incidence of BPD in youth with ASD is probably underestimated. BPD should be borne in mind if a child with ASD refers with episodic irritability and aggressive attacks and have a family history of BPD. In the light of the current literature, atypical

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antipsychotics seem to be more effective and tolerable than the mood stabilizers in children and adolescents with both ASD and BPD. There is an urgent need for randomized controlled trials with large samples, for the treatment of BPD in youth with ASD.

Keywords: autism spectrum disorders, mood disorder, comorbidity, treatment

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S13-S4


Psychopharmacological treatment difficulties and coping methods in hematology and cardiology consultations

Onur Burak Dursun

Ataturk University, Faculty of Medicine, Department of Child and Adolescent Psychiatry, Erzurum-Turkey e-mail address:

Psychiatric disorders co-occur at least in 1/3 of children with chronic health conditions. Additionally the risk for psychological adjustment problems in these children is nearly twice the risk of healthy children. Cardiologic and hematologic diseases are among the leading chronic health conditions of childhood and overlap with psychiatric problems in different areas. In this presentation, we’ll discuss the psychiatric aspects of most prevalent hematologic and cardiologic problems of childhood in the light of recent scientific literature. Keywords: child psychiatry, heart disease, hematologic disease

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S14


PET imaging in Alzheimer disease

Ebru Kanmaz Findikli

Kahramanmaras Sutcu Imam University, Faculty of Medicine, Kahramanmaras-Turkey e-mail address:

Alzheimer disease was first described in 1907 by Alois Alzheimer. From its original status as a rare disease, Alzheimer disease has become one of the most common diseases in the aging population, ranking as the fourth most common cause of death. Alzheimer disease is a progressive neurodegenerative disorder characterized by the gradual onset of dementia. The pathologic hallmarks of the disease are beta-amyloid (Aß) plaques, neurofibrillary tangles (NFTs), and reactive gliosis. Current diagnosis of Alzheimer disease is made by clinical, neuropsychological, and neuroimaging assessments. Developing new approaches for early and specific recognition of Alzheimer disease at the prodromal stages is of crucial importance. The search for therapies that can modify the course of AD to slow, delay, or prevent it is clearly the most important challenge. That search has in turn led to a search for imaging markers that can be used as outcomes in drug discovery and trials.

Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. PET scanning is a powerful imaging technique that enables in vivo examination of brain functions. It allows for noninvasive quantification of cerebral blood flow, metabolism, and receptor binding. PET scanning helps in understanding the disease’s pathogenesis, making the correct diagnosis, and monitoring the disease’s progression and response to treatment. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-D-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) , FDDNP, Florbetapir F 18 (AMYViD), flutemetamol F18 and their a combination have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process.

In the future, efforts to develop specific neuro ligands for neuropsychiatric diseases, may further enhance the sensitivity of PET scanning for early diagnosis of Alzheimer disease and may provide a biologic marker of disease progression.

Keywords: PET imaging, Alzheimer disease

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S14

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Biomarkers in Alzheimer’s disease

Burcu Yavuz

Acibadem Maslak Hospital, Istanbul-Turkey e-mail address:

In 1984, clinical diagnostic guidelines for probable Alzheimer’s Disease (AD) were created by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. The 1984 criteria have been successfully used for 27 years. In the past decade, molecular biomarkers have been developed. Hence, revised criteria were published in 2011 for the clinical diagnosis of AD, mild cognitive impairment due to AD, and preclinical AD.

It is well known that the pathological processes in the CNS of AD patients start more than a decade before the first symptoms of AD are noticed. Due to the advances in research, brain imaging and tests based on cerebrospinal fluid (CSF) biomarkers have been implemented to provide evidence of an ongoing pathophysiological progression of AD and it is also possible to make a pre-dementia diagnosis of AD. Reduced levels of beta-amyloid in the CSF, elevated levels of CSF tau or hyperphosphorylated tau are found in individuals with AD. Extracellular accumulations of amyloid β (Aβ) in senile plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau (P-tau), the total amount of tau (T-tau) which reflects the intensity of neuroaxonal degeneration are revealed as characteristic hallmarks of AD. Both cross-sectional and longitudinal studies have evaluated the association between the core CSF AD biomarkers and preclinical AD. CSF levels of Aβ42 alone or in combination with T-tau or P-tau have been associated with future development of cognitive impairment in cognitively normal individuals at the time of lumbar puncture. Increased T-tau: Aβ42 ratio or low levels of CSF Aβ42 have been found to predict conversion to minimal cognitive impairment in cognitively normal. A large multicenter study found that the combination of Aβ42:P-tau ratio and T-tau predicted a sensitivity of 83% and a specificity of 72% for progression to AD. Hansson et al. found that CSF level of Aβ42, T-tau and P-tau among MVI patients could predict progression to AD after a follow up period of 5.2 years. In differential diagnosis among other dementias, P-tau may have a greater value since it is more AD-specific. T-tau is not AD-specific since increase levels of T-tau are also seen in head trauma, disease or acute stroke.

Biomarkers may provide early disease detection and lead to effective early treatment of AD. Apart from the core biomarkers, there are several candidate biomarkers of CSF and blood hat need to be verified in future studies.

Keywords: Alzheimer’s disease, amyloidβ, tau, biomarker

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S15


Recognition and management of depressive symptoms in schizophrenia; past, present and future

Serdar Dursun, Glen Baker

Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Alberta-Canada e-mail address:

Mood and anxiety disorder-related psychopathology, including anxiety and depression are very frequently present in patients with schizophrenia. This co-morbid psychopathology can significantly influence appropriate psychiatric management.

In this presentation, the prevalence of depressive symptoms in schizophrenia will be presented and discussed. In particular, there will be a discussion on the origins of negative symptoms and how to possibly differentiate these symptoms from depressive symptoms in patients with schizophrenia.

Furthermore, the impact of depressive symptoms on prognosis of schizophrenia, its severity, patient functioning and quality of life, as well as relapse and chronicity, will also be presented. The presentation will then focus on psychopharmacological evidence to support the efficacy of atypical antipsychotic medications and other available treatments in this area, and how they can be used to increase remission rates, reduce the risk of relapse and enhance functional outcomes.

Keywords: depressive symptoms, schizophrenia

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S15

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Eating disorders in terms of neuroendocrine-molecular interaction

Selma Bozkurt Zincir

Erenkoy Mental Health and Neurology Training & Research Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:,

There are three basic pillars for the development of eating disorders: genetic predisposition, neuroendocrine-molecular changes in the brain and metabolic response to it. As an outcome of neuroendocrine research, a close relationship was found between neuroendocrine functions and symptom complexes of psychiatric disorders such as eating disorders and mood disorders. For example, in particular of eating disorders as well as hypothalamic dysfunction, there are also known to be some specific changes including hypothalamic-pituitary- adrenal axis and gonadotropin secretion. These changes may be primary or secondary. Monoaminergic neurotransmitter peptides, which play an important role in the pathogenesis of psychiatric diseases, also control synthesis and secretion of the some hypothalamic-pituitary hormones. Additionally, hypothalamic hormones, widely available in the brain, produce specific effects via receptors and influence the functional activity of the brain neurotransmitter systems. Many hypothalamic hormones are believed to co-ordinate more complex behavior and function of internal homeostasis.

Certain hormones, neurotransmitters and other molecules, which might have effect in particular of eating disorders can be listed as follows: estrogen, serotonin, leptin, alpha melanocyte stimulating hormone, cholecystokinin, dopamine, noradrenaline, ghrelin, BDNF, NMDAr, agouti-related protein, neuropeptide Y, opioids and their receptors, thiamine, zinc, omega-3 acids. In this presentation, main neuroendocrine-molecular changes and interactions that occurs in the eating disorders are mentioned.

Keywords: eating disorders, neuroendocrine changes, molecular interactions Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S16


Binge Eating Disorder

Alican Dalkilic

Temple University School of Medicine, USA e-mail address:

After first being described in 1959 as “night eating syndrome,” binge eating disorder (BED) is now included as a formal diagnosis in DSM 5. BED is the most prevalent eating disorder (ED) in adults, seen all ethnic and cultural groups, and has 2% and 3.5% lifetime prevalence in males and females, respectively. Clinicians should consider BED diagnosis in individuals with recurrent episodes of binge eating occurring once a week or more, lasting 3 months or longer and characterized both by eating definitely larger amount of food in a similar period and under similar circumstances than most people would eat and by a sense of lack of control over eating during the episodes. The person must experience marked distress regarding binge eating and episodes should be associated with at least 3 of the following: eating much more rapidly than normal, eating until feeling uncomfortably full, eating large amount of food when not feeling physically hungry, eating alone because of embarrassment, and feeling disgusted with oneself, depressed, or very guilty after overeating. BED cannot occur exclusively during the course of anorexia or bulimia nervosa.

Risk factors for BED include childhood obesity, depression, low self-esteem, abuse history in childhood, critical comments about weight, strict and yo-yo dieting, and possible genetic predisposition. People with BED do not only face more social difficulties and have lower quality of lives, but also are prone to development of obesity, obstructive sleep apnea, metabolic syndrome or its components including diabetes, cardiovascular, gastrointestinal, and high lipid problems. BED patients usually binge on foods that are high in fat, carbohydrate, and salt. They unexpectedly may have vitamin and mineral deficiencies.

Treatment approaches in BED can be categorized into: self-help approaches aiming to manage binge eating and weight, medical/ surgical interventions targeting underlying hormonal/metabolic problems, and psychopharmacological and psychological modalities aiming to address underlying and core symptoms and concurrent psychiatric conditions associated with BED. Bariatric surgery has been an effective tool in treating severe obesity, but obese patients with BED seem to have poorer outcomes and some continue to binge eat and gain weight after surgery. Cognitive behavioral therapy (CBT) can achieve 50% remission of binging and seems to be more effective than behavioral weight loss programs. Addressing comorbid psychiatric conditions, which reach as high as 60-70% in BED, by

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pharmacological tools and CBT would likely provide extra benefits. Some reviews have concluded psychotherapeutic modalities are superior to pharmacological interventions in BED, yet there is good evidence of efficacy for few antidepressant, antiepileptic, and other medications and anecdotal evidence for some other agents. In addition psychotropic medications are proven to be effective in treating comorbid mood, anxiety, trauma, and/or substance abuse disorders that are frequently associated with BED.

Unfortunately most health care providers including psychiatrists and psychologists do not screen for BED and not attempt to treat or refer patients with BED, despite it is a formal DSM 5 disorder that cause significant suffering and morbidity and can worsen co-occurring medical and psychiatric problems. Screening and assessing individuals for BED and concurrent conditions at clinics and providing evidence based treatment options would likely improve quality of lives of patients and overall outcomes in BED.

Keywords: binge eating disorder, psychopharmacological treatment, eating disorders, bulimia, anorexia Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S16-S7


Psychotropic drug interactions risk in daily clinical practice: a preliminary study on patients with schizophrenia spectrum disorders

Filiz Karadag

Gazi University, Faculty of Medicine, Department of Psychiatry, Ankara-Turkey e-mail address:

The chronic clinical course of schizophrenia, resistance to treatment, drug side effects, different responses of negative and cognitive symptom clusters to anti-psychotic medications with different receptor profiles may require combination therapy and thus antipsychotic poly-pharmacy. Although the frequency of poly-pharmacy may vary between 46% to 70% in different countries and years, most studies report antipsychotic poly-pharmacy in nearly half of the patients. Anti-psychotic poly-pharmacy was reported between 38.2 – 64.7% of patients with schizophrenia – spectrum of disorders in Turkey.

The aim of this report to present the data* about the drug interaction risks in the patients with schizophrenia spectrum disorders (schizophrenia or schizo-affective disorder) receiving antipsychotic treatment in a provincial area of Turkey reflecting real world conditions. As far as we know, no study was undertaken to investigate the risk of drug interactions that these patients may experience in Turkey. The baseline pharmacotherapy data of a prospective naturalistic study (Project Number: 2008TPF029) supported by the Committee of Scientific Research Projects of Pamukkale University were used in this report. The study sample consisted of 240 patients with schizophrenia spectrum disorders. Co-administration of antipsychotics and other psychotropic drugs for at least 4 weeks were recorded as poly-pharmacy. As individual treatment regiments all used medications for each patient, drug-drug interaction risks were evaluated via the internet site and; interaction information for healthcare professionals were used.

We found that 56.7% of our patients were under antipsychotic monotherapy, of 35.8% were treated with two antipsychotic medications. A total of 172 (71.7%) patients were taking medications with a risk of interaction, with 417 total drug interaction risks. 87.8% of the interaction risks were at a moderate level. Approximately one quarter of the patients (24.4%) were using medications with a major interaction risk. The majority of major interaction risks were QT prolongation (83.3%) risk, and 9.5% were risk of hypotension – serious bradycardia, 7.2% were the risk of changes in blood drug levels. Among the drug interactions risks related to QT prolongation, 26.2% had a warning of contra-indication. The medications with a risk of QT prolongation were ziprasidone, quetiapine, citalopram / escitalopram, clozapine and haloperidol. All of the major interactions that were related with drug blood levels consisted of quetiapine – carbamazepine interaction.

The present report suggested that an important percentage of patients are exposed to drug – drug interactions with ever increasing use of multiple medications in schizophrenia spectrum disorders, and among these interactions, most major risks were cardiovascular risks, and especially QT prolongation. Prospective studies with larger numbers of patients are needed in this topic.

Keywords: psychotropics, drug interactions, schizophrenia

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S17

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Treatment resistant patient and personalized medicine

Tayfun Turan

Erciyes University, Faculty of Medicine, Department of Psychiatry, Kayseri-Turkey e-mail address:

Today, in clinical practice, factors such as signs and symptoms of mental illness and prior treatments and probable side effects of drugs are taken into consideration when clinician decides a proper treatment for a patient. However, psychiatric patients may exhibit interindividual variability in their responses to psychotropic drugs. Nevertheless, it takes longer duration for diagnose or make differential diagnosis of an illness since some disorders may exhibit similar symptoms. Thus, this variability affects response duration, compliance, effective and toxic levels of drugs and even may cause unresponsiveness. A longer duration for a drug to reduce symptoms or resistance to treatment may lead to poor life quality, disabilities, morbidity and mortality. Moreover, poor response to one treatment does not mean poor response to others. In general, fifty percent of psychiatric patients exhibit, somehow, resistance to treatment. Personal and environmental factors such as stress, smoking, feeding, ethnic background, genetic history and patients’ genome influence treatment response.

Recently, research has focused on searching predictive factors, endophenotypes and biomarkers to help true diagnosis and to find a more effective treatment with less or no adverse effects. Endophenotypes are markers of an illness, which should not depend on clinical appearance symptoms that should be defined as a trait marker. Biomarkers are measurable characteristics that evaluate normal and pathogenic process, or response to treatment and may be a state or trait marker. For example, negative mood and anhedonia are endophenotypes for major depression, brain derived neurotrophic factors and oxytocin may be biomarkers for bipolar disorder, cognitive deficits such as verbal memory recall, executive functioning are endophenotypes for schizophrenia.

In recent years, significant advances have been made in the genetics of mental disorders. Genetic factors are target for personalized medicine to predict drug response and side effects. Most common psychotropics are substrates for CYP2D6, an enzyme, which belongs to cytochrome P450 enzyme family, to be considered as a biomarker. Because the genes coding cytochrome P450 enzymes are highly polymorphic, they lead to differential metabolism of psychotropics. The enzymes metabolic rates play a significant role in the efficacy and side effects of a psychotic drug. Therefore, ultra-rapid metabolizers may need high doses of substrates to be effective in treatment while poor metabolizers exhibit side effects even within normal dose ranges.

Genome-wide association studies (GWAS) have showed the relation between Single Nucleotide Polymorphisms SNPs) and common psychiatric disorders such as schizophrenia, major depression, bipolar disorder. There also may be an association between efficacy and side effects of psychotropics and SNPs. For instance, a GWAS identified an association between one single locus at rs17390445 (on chromosome4p15) and relief of positive symptoms with ziprasidone treatment.

In conclusion, the studies showed that inter-individual differences determined clinical response and side effects of a psychotropic agent. In the near future, it seems that genetic markers will be promising tools for personalized treatment.

Keywords: treatment resistant patient, personalized medicine, psychiatry

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S18


Changes about “trauma’’ and ‘’stress’’ in DSM-5

Suleyman Akarsu

Gulhane Military Medical Academy, Ankara-Turkey e-mail address:

DSM-5, The Diagnostic and Statistical Manual of Mental Disorders, was released at the American Psychiatric Association’s (APA) meeting in May 2013 that is the fifth major revision. In DSM-5, Posttraumatic Stress Disorder (PTSD) is no longer included in Anxiety Disorders and included in a new chapter as Trauma- and Stress¬or-Related Disorders. The Trauma-and-Stressor Related Disorders include Reactive Attachment Disorder, Disinhibited Social Engagement Disorder, Acute Stress Disorder, PTSD and Adjustment Disorders. Trauma- and Stress¬or-Related Disorders reflect the close relationship between anxiety disorders, obsessive-compulsive and dissociative disorders. DSM-5 eliminates the distinction between acute and chronic phases of PTSD. The patient must have PTSD symptoms that persist for at

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least 1 month after the traumatic event. The DSM-5 aimed to expand the definition of PTSD beyond the fear construct. DSM-5 draws a clear line about the traumatic event. The definition of trauma in PTSD indicates ‘’Exposure to actual or threatened death, serious injury, or sexual violence.’’ Sexual assault is specifically included. PTSD patients can be the actual victim or witness. Exposure to the trauma through electronic media, television, movies, and pictures is not considered as PTSD unless these traumatic events are work-related. There are four PTSD symptom clusters (There were three in DSM IV) a) Intrusion symptoms including dissociative reactions (dissociative reactions are flashbacks, derealization, and depersonalization.) b) avoidance symptoms c) Negative alterations in mood and cognitions (dysphoric type) d) alterations in arousal and reactivity. To satisfy the criteria for PTSD, there must be a minimum number of symptoms from each cluster: at least one of five re-experiencing symptoms, one of two avoidance symptoms, three of seven cognitions and mood symptoms, and three of six hyperarousal symptoms.

The number of symptoms increased from 17 in DSM-IV to 20 in DSM-5. There are new symptoms, namely persistent negative beliefs and expectations about oneself or the world, persistent negative trauma-related emotions, and risky or reckless behaviors. Diagnostic criteria have been suitable for children and adolescents. Separate criteria have been added for children aged 6 years or younger. Thus, there is not a separate child section in DSM-5.

Keywords: DSM-5, trauma, stress, changes

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S18-S9


Effect of DSM-5 changes on clinical applications of trauma related disorders

Taner Oznur

Gulhane Military Medical Academy, Department of Psychiatry, Ankara-Turkey e-mail address:,

Given the incidence of encountering with traumatic life events and mental illnesses that are developing after trauma in the community, importance of the diagnosis of trauma-related disorders is emerging. Therefore, it is necessary to follow the changes in current diagnostic manuals. A number of diagnostic criteria have been changed with the publication of DSM-5 in May 2013. Specific diagnostic criteria have been defined for young children. While trauma-related diseases have been defined within anxiety disorders in DSM-IV, they are now being defined as a new individual set of diagnosis in DSM-V. The number of symptoms described in trauma related disorders was increased to 20 by the introduction of DSM 5. The number of symptom clusters defined for posttraumatic stress disorder (PTSD) has increased to four from three. The criteria of experiencing intense fear, anxiety and helplessness after the trauma and the acute and chronic markers (definitions) have been removed. Preschool and dissociative subtypes have been identified. In addition, unexpected loss of family members and relatives of the person due to natural causes have been removed from being a diagnostic criterion. Moreover, presence of at least one avoidance symptom has been set as a requirement for the diagnosis. All these changes in the diagnostic criteria are being estimated to reduce the rates of PTSD. On the other hand, it was noted that the redefined concept of PTSD by DSM- 5 have more overlap with complex PTSD diagnosis, which is a quite acceptable concept in trauma psychology.

Keywords: DSM-5, trauma related disorders

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Did intended changes for DSM-5 achieve the purpose of post-traumatic stress disorder?

Abdullah Bolu

Eskisehir Military Hospital, Eskisehir-Turkey e-mail address:

One of the main changes in DSM-5 is associated with for post-traumatic stress disorder (PTSD). Previously (DSM-IV), PTSD were classified under the anxiety disorders group. In DSM-5, It is classified under the main heading of “trauma and stressor-related disorders” with

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psychiatric disorders with common etiological factors.

Diagnostic criteria of PTSD are now grouped under five main titles with DSM-5. These main titles are summarized as; having a serious trauma (A), re-experiencing the trauma (B), avoidance symptoms (C), negative cognition, mood related symptoms (D), aggressiveness, and hyperarousal symptoms (E).

Changes associated with the definition of traumatic event which causing psychiatric disorder are made. Definitions about subjective components of traumatic event in DSM-IV were removed, but instead it, definitions, which will help to identify the traumatic event were added. Briefly, criterion A (the traumatic event) has been tried to purify from subjective components and traumatic events were described in an objective way. Definition has been expanded, since items related with the impact of event over the patient have been removed. Diagnostic criterion B is simplified with DSM-5. Borders of diagnostic criteria B were clarified with a definition of re-experiencing comprising dissociative features.

According to new criteria, diagnostic criterion C was completely organized as an item related to avoidance. Mood-related items were removed. Some authors have interpreted this situation as clearing the borders between PTSD and other mental disorders and highlighting the mood features of PTSD.

Criterion D consists new forms of mood symptoms and negative cognitions which took part in the old diagnostic criteria. According to some authors, mood symptoms in PTSD had the opportunity of expanded definition with these criteria.

E criterion carries the nature of a novelty for PTSD. By this criterion, aggression and impulsivity of patients with PTSD which are frequently encountered, are set out in a clear format.

PTSD identification in DSM-5 (especially criteria D and E) has been targeted to explain of many symptoms of patients without the need for some comorbid diagnosis. Unlike symptoms of anxiety in the DSM-IV, depressive symptoms were clearly defined. Remaining of anxiety symptoms so behind of depressive symptoms or the expression of depressive symptoms so clearly bring to mind the question that have DSM-5 tried to create compelling reasons to the fundamental change in the classification. Rigid and clear statements were used rather than more inclusive and expanded changes for the description of the traumatic event.

Another significant change in DSM-5 is identification of dissociative subtype. It is considered the identification of this subtype based on the hypothesis that some people’s reactions to traumatic events are mainly in the form of dissociative reactions so that they reveal a coping strategy with intense anxiety and fear. In one aspect, this definition create open field to neurobiological studies and treatment- related researches, on the other hand it may cause legal problems. Even, there are comments that this situation might cause secondary gains.

These new criteria will be tested more accurately by clinical practices and studies. PTSD prevalence is reported to be similar in terms of DSM-IV and DSM-5 diagnostic criteria

Keywords: DSM-5, posttraumatic stress disorder

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S19-S20


Vitamins in the treatment of psychiatric diseases and their mechanisms of action

Hayriye Baykan

Balikesir University, Faculty of Medicine, Department of Psychiatry, Balikesir-Turkey e-mail address:

Vitamins are organic molecules that are required for health, growth and reproduction. Human body is unable to synthesize adequate amounts of vitamins, except vitamin D. Therefore, they should be obtained through diet via foods or supplements. Vitamin deficiencies are generally due to malnutrition, on the other hand, toxicity is usually due to over usage of vitamin supplements. Drug interactions may also effect serum vitamin concentration. For example, anticonvulsant therapy may result in deficiency of folic acid, or proton pump inhibitors may decrease the absorption of Vitamin B12.

Vitamins are also important in maintaining the mental health. Vitamin B9 (folate), Vitamin B12 (cobalamine), Vitamin B1 (thiamine), Vitamin B6 (pyridoxine) and vitamin E deficiencies have been known to cause mental dysfunction. Thiamine is essential for pentose-phosphate pathway and oxidative decarboxylation reactions and is important for brain functions. Wernicke’s encephalopathy and Korsakoff’s psychosis caused by thiamine deficiency. Vitamin B2 (riboflavin) is required as a cofactor (FMN and FAD) for many of the enzymes in human metabolism. Pyridoxine has a critical role in synthesis of many neurotransmitters (dopamine, noradrenaline, adrenalin, serotonine, histamine, GABA) associated with mental functions. Decreased levels of pyridoxine are usually seen in alcoholics, which lead to epileptic seizures, EEG abnormalities, depression and confusion. Vitamin B9 (folic acid) plays a basic role in one carbon metabolism and act as a

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cofactor for serotonin, noradrenaline, dopamine, DNA and phospholipid synthesis. Many of the studies showed that low folic acid levels are associated with mood disorders. Deficiency of Vitamin B12 (cobalamine) causes both neurological and hematological pathologies. Acting as a coenzyme in one-carbon transfer reactions, cobalamine deficiency is highly related to demyelination defects. Folic acid and vitamin B12 deficiencies may result in impaired synthesis of purine and pyrimidine bases. Hematologic findings of vitamin B12 deficiency may be masked by high doses of folic acid ingestion, but this condition will not delay psychiatric symptoms. Vitamin C has also a critical role in biosynthesis of neurotransmitters and it is essential for brain functions.

However, association between mental disorders and some of the other vitamins is not well established yet. Further investigations are needed to explain relationship between vitamins and psychiatric disorders.

Keywords: psychiatric disorders, vitamin

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S20-S21


Which one is fluctuating? hormones or emotions?

Esra Yazici

Kocaeli Derince Training and Research Hospital, Department of Psychiatry, Kocaeli-Turkey e-mail address:

The lifetime prevalence of mood disorders in women is approximately twice that of men. The underlying causality of this gender difference is not well understood. There is increasing scientific attention to the modulation of the neuroendocrine system by fluctuating gonadal hormones. This presentation attempts to summarize our current state of knowledge on the role and potential relevance of estrogen and other sex steroids to psychiatric disorders specific to women from menarche to menopause as a general topic.

Although genetic, psychosocial and environmental factors clearly contribute to an individual’s risk for depression and other mood disorders, substantial experimental data support an independent role for hormonal influences on the expression of mood symptoms. Estrogen is a potent neuromodulator and is known to alter the activities of multiple neurotransmitter systems including those involved in major depressive disorder. Unlike men, neurons throughout the female brain must be able to respond to the effects of rapid increases and decreases in estrogen levels that occur during the menstrual cycle. It is shown that ovarian hormones can alter synaptic plasticity in female rats and in further researches it is under-stood that neuronal function is fluid and dynamic and is programmed to respond to predictable changes in ovarian hormones during the reproductive period.

The sudden appearance of higher levels of estrogen in puberty alters the sensitivity of the neurotransmitter systems. Moreover, the constant flux of estrogen and progesterone levels throughout the reproductive years, proceeds constant modification of the neurotransmitter systems. Premenstrual syndromes may be the result of an altered activity or sensitivity of certain neurotransmitter systems. Pregnancy and delivery produce dramatic changes in estrogen and progesterone levels as well as significant suppression along the HPA axis, possibly increasing vulnerability to depression. At menopause, estrogen levels decline while pituitary LH and FSH levels increase. The loss of modulating effects of estrogen and progesterone may underlie the development of perimenopausal mood disorders in vulnerable women.

All these results suggest a certain relationship between hormones and mood disorders and in recent studies role of hormones in treatment of mood disorders is discussed. Further studies may present a better understanding and treatment options about reproductive hormones and mood disorders especially ‘reproductive depression.

There are many studies about the relationship between hormonal fluctuations and mood disorders but there are few studies about the relationship between affective temperaments and reproductive cycles. Affective temperaments are known as antecedents of mood disorders so as mood disorders; affective temperaments may be awaited to have a concurrence of simultaneous fluctuations with hormones. Opening a preview to several projections of hormonal fluctuations to mood changes as well as projections of mood changes to hormonal fluctuations is aimed in the presentation. Affective temperaments, mood disorders and hormones are the subtopics and all will be discussed in the lightening of their interactions.

Keywords: hormone, mood, depression, affective temperament Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S21

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Women suffering from depression

Neriman Aras1, Elif Oral2, Nazan Aydin3, Ismet Kirpinar4

1Kanuni Research and Training Hospital, Department of Psychiatry Trabzon-Turkey

2Ataturk University, Faculty of Medicine, Department of Psychiatry, Erzurum-Turkey

3Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital Department of Psychiatry, Istanbul-Turkey 4Bezmialem Vakif University, Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey

e-mail address:

Several factors have been considered to be the contributors for depression. Perinatal period is important for vulnerability to depressive disorders. Prevalence of Postpartum Depression changes between 14-29% in Turkey. Lifetime prevalence of Major Depressive Disorder is high in Eastern Turkey. Therefore, the real prevalence of postpartum depression is still unknown. We aimed to evaluate the depressive disorders and associated factors in a large sample of reproductive age women, who are not in prenatal or postnatal period.

We used General Health Questionnaire-28 and Edinburgh Postpartum Depression Scale as screening tests in 589 women between the ages of 15-49 in Erzurum. Associated factors were established with the socio-demographic questionnaire. Prevalence of Depressive Disorders was determined by SCID-I, severity of depression was assessed with Hamilton Rating Scale for Depression. General Assessment of Functionality, Brief Disability Scale, and Scale of Perceived Social Support from Family were administered to evaluate functionality, disability and social support.

Results of the study showed that 32.8% of women had Depressive Disorders. Being a widow or divorced, having low levels of education and income, being a housewife or worker, marriage and giving birth at an early age, having an unemployed spouse and possessing three or more children were associated with Depressive Disorders. While 84.0% of women who were diagnosed with depressive disorders presented with mild or moderate depression, 82.9% of them appeared to suffer from disability. We found a negative correlation between functionality, social support and severity of depression.

Since there is a high prevalence of Depressive Disorders throughout a woman’s life, it is extremely important to consider all periods in terms of diagnosis and treatment.

Keywords: depressive disorders, reproductive age, women

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S22


Women suffering from depression

Neriman Aras1, Elif Oral2, Nazan Aydin3, Ismet Kirpinar4

1Kanuni Research and Training Hospital, Department of Psychiatry Trabzon-Turkey

2Ataturk University, Faculty of Medicine, Department of Psychiatry, Erzurum-Turkey

3Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital Department of Psychiatry, Istanbul-Turkey 4Bezmialem Vakif University, Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey

e-mail address:

Several factors have been considered to be the contributors for depression. Perinatal period is important for vulnerability to depressive disorders. Prevalence of Postpartum Depression changes between 14-29% in Turkey. Lifetime prevalence of Major Depressive Disorder is high in Eastern Turkey. Therefore, the real prevalence of postpartum depression is still unknown. We aimed to evaluate the depressive disorders and associated factors in a large sample of reproductive age women, who are not in prenatal or postnatal period.

We used General Health Questionnaire-28 and Edinburgh Postpartum Depression Scale as screening tests in 589 women between the ages of 15-49 in Erzurum. Associated factors were established with the socio-demographic questionnaire. Prevalence of Depressive Disorders was determined by SCID-I, severity of depression was assessed with Hamilton Rating Scale for Depression. General Assessment of Functionality, Brief Disability Scale, and Scale of Perceived Social Support from Family were administered to evaluate functionality, disability and social support.

Results of the study showed that 32.8% of women had Depressive Disorders. Being a widow or divorced, having low levels of education

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and income, being a housewife or worker, marriage and giving birth at an early age, having an unemployed spouse and possessing three or more children were associated with Depressive Disorders. While 84.0% of women who were diagnosed with depressive disorders presented with mild or moderate depression, 82.9% of them appeared to suffer from disability. We found a negative correlation between functionality, social support and severity of depression.

Since there is a high prevalence of Depressive Disorders throughout a woman’s life, it is extremely important to consider all periods in terms of diagnosis and treatment.

Keywords: depressive disorders, reproductive age, women

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S22-S3


Menstruation and premenstrual dysphoric disorder

Elif Oral

University of Michigan Health System, USA e-mail address:

Since Hippocrates, it was defined that premenstrual changes such as sense of weight, headache, tinnitus, and be seen as small spots in front of eyes. Premenstrual syndrome (PMS) is a term that is commonly used to describe a group of emotional, behavioral, and physical symptoms that occur for several days before menstrual bleeding and calm during the menstruation. Premenstrual Dysphoric Disorder (PMDD) is severe form of PMS. PMS occurs in 20–32 % of premenopausal women, and PMDD affects 3–8 % of premenopausal women. Modern studies related with PMS started with Robert Frank in 1931. Various biological and psychological factors have been proposed to cause PMDD, including the absence of progesterone, abnormal serotonin function, altered endorphin modulation of gonadotropin secretion, lack of exercise, and poor dietary habits. Recently, it has been suggested that the cyclical course of PMS could be the result of a complex chain of psycho-neuroendocrine events triggered by normal ovulation rather than hormonal imbalance. PMDD described in the chapter of depressive disorders in DSM-V. We have two studies related with PMDD and PMS published in recent years; firstly, we scanned to the prevalence, clinical features and functionality in PMS within population of Atatürk University Medical Faculty. Severe PMS was found in 5.5% of the participants. According to our results, level of higher carbohydrate and junk food consumption and dysmenorrhea were related to higher premenstrual symptom scores. The presence of dysmenorrhea was significantly correlated with poorer school performance, including class attendance and/or concentration difficulties during class and exam performance/exam attendance. In our second study, participants diagnosed as PMDD with two prospective assessments of consecutive menstrual periods had significantly higher luteal serum BDNF and HSP70 levels compared with controls, and there was a significant positive correlation between serum BDNF and HSP70 levels. Premenstrual symptoms are one of the most common problem areas and PMDD is one of the depressive disorders of young women that adversely affect their academic performance and emotional status.

Keywords: premenstrual syndrome, premenstrual dysphoric disorder, menstruation Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S23


Cognitive functions in patients with obsessive compulsive disorder

Pinar Cetinay Aydin

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Istanbul-Turkey e-mail address:,

The literature related to cognitive dysfunction in OCD is primarily focused on executive dysfunction. Most psychology studies on OCD have examined information-processing bias. OCD researchers analyze cognitive function based on neuropsychology testing and clinical observation in the psychiatry. The literature concerning differences in verbal memory performance between OCD patients and healthy controls is inconsistent. Verbal memory performance is different in OCD patients, as they code words during objective verbal memory

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tests, whereas healthy individuals tend to use an organizational strategy, such as semantic relationships. OCD patients have difficulty formulating an organizational strategy, but are able to implement one once formulated. The inability to formulate an organizational strategy for information coding might be related to executive dysfunction.

Executive dysfunction appears to be the primary cognitive deficiency in OCD patients. Deficiencies related to memory are associated with faulty information processing and poor organizational strategy implementation. Most studies have reported that executive functions, including set shifting, verbal fluency, planning, and decision-making, are similar in OCD patients and controls. In addition, it is known that OCD patients make more perseverative errors, have more difficulty using feedback, and have delayed response during neurocognitive testing, all of which might be related to slow cognition or an increase in compulsive behavior in an effort to avoid making mistakes. The findings of neuroimaging studies support the existence of dysfunction in the frontostriatothalamic pathway in OCD. Response inhibition and decision-making are cognitive functions that should be the target of future OCD research.

Keywords: obsessive compulsive disorder, cognitive function, memory, attention, executive function Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S23-S4


Psychopharmacologic approaches in depression treatment

Etem Erdal Ersan

Sivas Numune Hospital, Sivas-Turkey e-mail address:

Depression is one of the most common psychiatric diseases. Depression affects about one in ten people. Disability associated with depression is one of the most important health problems. Today, the most important approach in depression treatment is psychopharmacology. There are clinical and experimental studies to develop more effective treatment strategies. There is no consensus on individual treatment because the treatment response and its duration are varied between patients. There are no significant differences in terms of efficacy between antidepressant medicines. The treatment targets should be identified and the most suitable one should be preferred according to the patients’ characteristics. 1) Definite diagnosis, 2) If possible, symptoms (eg: Agitation, insomnia, memory problems) 3) the prognosis should be assessed carefully. Acute treatment should be administrated for active symptoms, maintained treatment should be administrated to prevent early recurrence, and protective treatment should be administrated to decrease the number of relapses and depression severity. In this presentation, we present you the treatment objectives, and the most important features of psychopharmacologic agents,we use.

Keywords: depression, treatment, psychopharmacology

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New horizons in the treatment of depression

Hulya Turgut

Bilecik State Hospital, Bilecik-Turkey e-mail address:

In the treatment of depression, the target is the elimination of depressive symptoms, the acquisition of (regaining) functionality, and the prevention of relapses and recurrences. In the treatment of depression, in certain cases, it may become necessary to implement somatic therapies in addition to psychopharmacological and psychotherapeutic methods. .

Of these treatments, the following are the main ones are as follows: electroconvulsive therapy (ECT), magnetic seizure therapy (MST), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial direct current stimulation (tDCS) and chronotherapeutic approaches such as sleep deprivation, sleep phase advance and light therapy.

ECT is a treatment method whose efficacy in the treatment of many psychiatric disorders has been proven. Its administration is based on

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the principle of creating generalized convulsions by stimulating brain tissue with electrical current. MST is a new treatment method that uses high doses of rTMS in order to induce seizures. MST is administered under anesthesia. MST seizures have shorter duration compared to ECT. It has been reported that MST causes fewer cognitive side effects. TMS is a technique aiming to generate low-level transient electric current in the cerebral cortex by a very strong magnetic field induced by a stimulating coil. TMS may change regional activities in the cortex by revealing cortical blood flow and cortical metabolic changes. When directly administered, TMS can lead to changes in gene expression patterns. In a study conducted with TMS, it was determined that the c-fos expression led to increases in thalamic paraventricular nucleus in mice. If TMS is administered repetitively and rhythmically, it is called rTMS. VNS is based on the stimulation of the vagus nerve.

DBS shows its effect with the current generated with an electrode inserted in a small hole drilled in the skull. tDCS is performed by stimulating cortical neurons via low amplitude 1-3 mA current sent by the electrodes placed on the scalp. If sleep disorders frequently accompany depression, then sleep deprivation and sleep phase advance methods are considered. Once fully implemented, sleep deprivation provides an antidepressant effect. In light therapy, the importance of circadian rhythms is focused in terms of the biochemical, neuroendocrine and behavioral physiology. Externally applied light and light-dark cycles are the most important factors that regulate circadian rhythms. In practice, a broad-spectrum white light is the gold standard. In ideal applications, 10,000 lux of light is applied at least 30 minutes.

Keywords: depression, new methods, psychiatric somatic therapies Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S24-S5


Personalized treatment for depression

Orhan Dogan

Dogus University, Istanbul-Turkey e-mail address:

The response ratio for the drug treatment of depression is between 30-50%. In the first line treatment of depression, different antidepressants have similar efficacy in moderate depression, to that of antidepressant medication combined with specific psychotherapies. In order to provide personalized treatment for depression, it must be identified characteristics of individual. The principle of “There is not illness, there is patient” that it has been emerged before almost one hundred years, has been formed the basis of personalized treatment. Numerous factors affect the response to drug treatment and to psychotherapy. In the previous studies, these factors have been evaluated according to outcomes of treatment as retrospectively. In these times, it is accepted that the success of treatment depends on personalized treatment. The evidences are necessary for this application.

The better and more specific interventions are known as personalized medicine. In psychiatry, this approach includes the predictors of treatment response such as biological, genetic, behavioral, experiential, clinical, and environmental factors.

The aims of personalized treatment are to select the most appropriate drug for depression, to arrange therapeutic doses, to identify treatment efficacy, to predict side effects and drug interactions.

The predictors for personalized treatment could not yet be identified. The studies on this issue may review as follows:

1. Individual predictors: age, gender, genetic characteristics, metabolic rate (phenotype), personality structure, stressful or traumatic life events, patient treatment preference, family history of treatment response, adherence.

2. Clinical predictors: the subtypes of depression, clinical symptoms, comorbid illnesses, response of past treatment.

3. The characteristics of antidepressant: the pharmacodynamics and pharmacokinetic characteristics of antidepressant, mechanism of action, side effects, drug interactions.

4. The type of psychotherapy: interpersonal or cognitive therapy, relationship with the other features.

5. Biochemical and neuroendocrine predictors: neurotransmitter production or metabolism, receptor polymorphism, hypothalamic- pituitary-adrenal axis measures, urinary 3-methoxy-4-hydroxyphenylglycol, serotonergic measures in serum/platelets, dexamethasone- corticotropin releasing hormone tests,

6. Inflammatory predictors: cytokines, tumor necrosis factor-alpha, interleukin (IL)-1-beta, and IL-6, C-reactive protein,

7. Neuroimaging and physiological predictors: auditory evoked potentials, quantitative EEG, PET and fMRI studies,

8. Predictors of molecular genetics: Genetic factors affect the variation of response to drug treatment; they contribute for about 50% of side effects. Pharmacogenomics use the data emerged from the human genome to identify new targets for treatment and to predict drug responses. The elucidation of gene-environment interactions may help to understand the pathophysiology of depression and may provide predictors for a personalized depression treatment.

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The studies regarding these probable predictors have not satisfactory results. The causes:

1. For personalized treatment, it may be necessary the larger sample than in traditional clinical trials.

2. To identify person-level predictors of treatment response may need to consider response across multiple episodes of depression.

3. To predict response to specific treatments may require combinations of several weak predictors rather than a single powerful one. Replication is the first step in translating research findings to clinical tests or predictors. Even after replication, while use them must be careful. There is necessity numerous and various studies for personalized treatment for depression. When the predictors are identify, it will provide early diagnosis, more efficient treatment, less side effects, the shorter illness duration, higher remission rate.

Keywords: depression, personalized treatment, predictors, drug treatment, antidepressants, psychotherapies

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S25-S6


All that glitters isn’t gold: Differential diagnosis of first episode psychosis

Alpay Ates

Gulhane Military Medical Academy Haydarpasa Training Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:

Schizophrenia disrupts social and family relationships, resulting severe educational and occupational impairment, lost productivity, physical illness, and premature mortality. A wide range of non-psychiatric medical conditions and a variety of substances can induce symptoms of psychotic disorders and catatonia. These are medical and neurological disease which consist of substance induced, epilepsy, neoplasm, cerebrovascular disease or trauma, AIDS, B12 deficiency, carbon monoxide poisoning, Creutzfeldt-Jakob disease, heavy metal poisoning, herpes encephalitis, homocystinuria, Huntington’s disease, neurosyphilis, pellagra, systemic lupus erythematosus, Wernicke- Korsakoff syndrome, Wilson’s disease etc.

When evaluating a patient with psychosis, clinicians should follow the general guidelines for assessing non-psychiatric conditions. First, psychiatrists should aggressively pursue undiagnosed non-psychiatric medical condition when a patient exhibits any unusual or rare symptoms or any variation in the level of consciousness. Second, psychiatrists should attempt to obtain a complete family history, including a history of medical, neurological and other psychiatric disorders. Third, psychiatrists should consider the possibility of a non- psychiatric medical condition, even in patients with previous diagnoses of schizophrenia. A patient with schizophrenia is just as likely to have a brain tumor that produces psychotic symptoms.

Differential diagnosis of schizophrenia symptoms should be considered other psychotic disorders. The psychotic symptoms of schizophrenia can be identical with those of schizophreniform disorder, brief psychotic disorder, schizoaffective disorder, and delusional disorders. There is a precipitating traumatic event in brief psychotic disorder. When a manic or depressive syndrome develops concurrently with the major symptoms of schizophrenia, schizoaffective disorder is the appropriate diagnosis. Non-bizarre delusions present for at least one month without other symptoms of schizophrenia or a mood disorder warrant the diagnosis of delusional disorder.

In this presentation, differential diagnosis of first episode psychosis will be reviewed based on the existing studies and general principles. Keywords: psychosis, differential diagnosis, schizophrenia

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S26


Dependency and attachment from psychodynamic perspective

Serhat Citak

Erenkoy Mental Health and Neurology Training and Research Hospital, AMATEM, Istanbul-Turkey e-mail address:

Attachment research has repeatedly shown the influence of early social interactions on developing inner working models and object representations that substantially impact on bonding behavior, subject-environment-interactions and psychopathology in later life.

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According to Bowlby’s conceptual description, interactions of genetic, neurobiological, and developmental factors contribute to the establishment of neuronal networks involved in the regulation of stress resilience, anxiety sensitivity and personality development. All three variables must therefore be supposed to contribute to the development of certain psychopathologies or even psychiatric disorders under certain circumstances.

Ainsworth et al. first described different behavioral patterns, so-called “attachment styles” which have subsequently been implemented in various reliable and valid rating scales for the differentiation between individual attachment styles (secure, insecure avoidant, insecure anxious, insecure ambivalent and disorganized). Several reports indicate a higher prevalence of insecure compared to secure attachment styles in alcohol and substance addiction and other psychiatric disorders. If this available and reliable attachment is experienced insufficiently, the individuals coping of stress or anxiety is therefore less effective and this may activate epigenetic mechanisms promoting onset of psychiatric disorders later on. Additionally, insecure attachment styles may go along with the development of distinct potentially dysfunctional behaviors in social interactions promoting the development of dysfunctional personality styles or personality disorders. This dysfunctionality is related to a higher incidence of addictive disorders.

Wedekind et al. found in alcohol-addicted inpatients, a correspondence of insecure attachment styles with high trait anxiety, more dysfunctional anxiety coping and dysfunctional personality styles. Their results imply the potentially high importance of attachment style in the characterization of alcohol dependency because of its possible high relevance for psycho- therapeutic strategies, individual therapeutic abilities and comorbid conditions. By separation into attachment styles, significant differences in potentially dysfunctional personality styles can be observed, giving a more differentiated characterization of groups than by diagnosing personality disorders exclusively. Clinical routine may profit from attachment style assessments. Insecure attachment styles in alcohol dependence may contribute to poorer outcome due to dysfunctional personality styles and anxiety coping behavior.

Earlier studies on attachment and substance use disorders using the Hazan and Shaver self-report mainly indicate a link with “avoidant” attachment styles. Schindler et al. found that, fearful attachment was predominant in drug dependent adolescents, while controls were predominantly secure. Severity of drug use was positively correlated with fearful attachment, but negatively correlated with dismissing attachment. The presence of comorbid psychiatric disorders was associated with fearful attachment but not with addiction severity.

In another study, Schindler et al. found that, opioid abusers were mainly fearful-avoidant, ecstasy abusers were preoccupied, fearful- avoidant and dismissing-avoidant, cannabis abusers were mainly dismissing and secure, and controls were mainly secure. Based on the self-medication hypothesis, they concluded that the preferences for specific substances were influenced by specific attachment strategies. Opioid seems to be used as an emotional substitute for lacking coping strategies. Cannabis seems to be used to support existing deactivating and distancing strategies. Ecstasy abuse was related to insecure attachment but not to a specific attachment strategy.

Keywords: attachment, dependency, psychodynamics

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S26-S7


Therapeutic drug monitoring

Eylem Ozten

NPIstanbul Neuropsychiatry Hospital, Istanbul-Turkey e-mail address:

Therapeutic Drug Monitoring (TDM) is a valid tool to optimize pharmacotherapy. Individualization of pharmacotherapy is essential in order to optimize efficacy and minimize toxicity, especially for compounds with narrow therapeutic index. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists involved in psychotropic drug analysis to optimize the use of TDM of psychotropic drugs. Five research- based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: 1-strongly recommended 2-reommended 3-useful 4-probably useful 5-not recommended.

Cytochrome P450 phenotyping has been valuable research tool and a way of assessing the genetic basis of metabolic capacity. Phenotyping allows estimation of the total influence of drug interaction, genetic polymorphisms, hepatic disease and other factor altering pharmacokinetics.

There are characteristic benefits of different methods to assess the pharmacokinetics of psychotropic drugs in clinical practice. TDM measures current plasma concentration and hence summarizes the effect of all pharmacokinetic influence, determines the phenotype for the drug currently in use, detects interaction with co-administered drugs. Phenotyping predicts metabolic capacity, provides information

Scientific Program Abstracts

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about metabolic capacity for a variety of drugs, detects interaction by co-administered drugs. Genotypingas a specific method for mutation, predicts metabolic capacity, provides information about metabolic capacity for a variety of drugs, helps to differentiate noncompliance, and the acquired information has a lifelong validity.

Keywords: therapeutic, drug monitoring

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S27-S8


Use of therapeutic drug monitoring in treatment of depression and antidepressant combinations

Gokben Hizlisayar

Uskudar University, NPIstanbul Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:,

Although there is sufficient evidence for the benefits of therapeutic drug monitoring (TDM) in optimizing antidepressant therapy, its widespread use in routine care is far from optimal. In clinical practice, in antidepressant drug dose optimization is often guided by a trial-and-error dose titration strategy. The importance of therapeutic drug monitoring of SSRIs is the subject of controversial discussion. However, TDM offers information about drug interactions, insufficient therapeutic effect, side effects, compliance and overdose.

Genetic influences on metabolism are most salient for antidepressants that have a low therapeutic index. TDM has been reported to increase not only efficacy and safety of antidepressant treatment, but also cost-effectiveness. Tricyclic antidepressant (TCAD) use in the treatment of depression is limited by their greater risk of overdose, potential effects on cardiac conduction. TCAD’s may lead to toxic plasma levels producing anticholinergic, cardiac, and CNS effects. The toxic levels of most TCAD’s are only two times therapeutic levels. Although the SSRI have a broad therapeutic index so that most patients are able to tolerate wide fluctuations in plasma levels due to pharmacokinetic interactions and can influence toxicity of co-administered drugs that are metabolized via this system.

The SSRIs are the most commonly prescribed antidepressants. They are generally well tolerated but have sexual adverse effects, increase the risk of hyponatremia, bleeding, stroke, and death in the elderly. All of the SSRIs are primarily eliminated by cytochrome P450 catalyzed oxidation in the liver. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19. For this reason, clinically relevant interactions may be expected when these antidepressants are co-administered with substrates of the pertinent forms, particularly those with a narrow therapeutic index. Duloxetine and bupropion are inhibitors of CYP2D6. Both the practitioner and the patient need to be aware of the potential risks of using a combination strategy and should set up an active monitoring system, which may include service of TDM.

TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has published literature-based guidelines for optimal use of TDM in psychiatry. AGNP recommends regular monitoring of plasma concentrations under maintenance therapy, at least every 3-6 months, to prevent relapses and rehospitalizations. The frequency of TDM requests may be increased if patients are known to be non-adherent to the medication or in case of changes of co-medications or of smoking (CYP1A2 substrate such as duloxetine) that affect the pharmacokinetics of the drug.

Combining antidepressants is a recognized step for those failing to respond to monotherapy. Despite the limited evidence base, this strategy is widely used by clinicians in practice. Not every combination used clinically is safe, and the use of such combinations may increase the side-effect burden without any additional advantage to the patient.

Keywords: antidepressant, combination, therapeutic drug monitoring

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Is therapeutic drug monitoring adequate in prediction of clinical response in psychiatric cases? find out more about P glycoprotein

Isil Gul

Uskudar University, NPIstanbul Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:

To obtain optimal results than pharmacotherapy, therapy with the purpose to make personalized methods used has been increasing in recent years. These methods relates to detecting changes in pharmacokinetics and pharmacodynamics. P glycoprotein (P-gp) and enzyme systems (CYP) responsible for drug metabolism due to genetic factors are changes in drug pharmacokinetics. The P-glycoprotein multi drug transporter (P-gp, ABCB1) is a member of the ABC (ATP-binding cassette) super family. In vitro and in vivo studies have demonstrated that P-gp plays a significant role in drug absorption and disposition because of its localization, P-gp appears to have a greater impact on limiting cellular uptake of drugs from blood circulation into brain and from intestinal lumen into epithelial cells than on enhancing the excretion of drugs out of hepatocytes and renal tubules into the adjacent luminal space. For instance, induction of the intestinal P-gp activity can cause reduced bioavailability of orally administered drugs and decreased therapeutic efficacy. On the other hand, the inhibition of the intestinal P-gp activity can lead to increased bioavailability, thus leading to an increased risk of adverse side effects. The brain uptake of the majority of antidepressants and antipsychotics, as well as many other psychotropic drugs and endogenous compounds are hampered by the activity of P-gp. In this presentation, we discuss the current state of knowledge concerning the role of P-gp on pharmacokinetics of psychiatric drugs and the impact of modulation of P-gp on major psychiatric disorders. Relevant issues in reference to the function of P-gp and other efflux pumps in the blood-brain barrier related to mood disorders and schizophrenia are addressed, such as a possible role of P-gp as a susceptibility factor in depressive disorders and psychotic disorders.

Keywords: P glycoprotein, pharmacokinetics, blood-brain barrier, psychiatric drugs Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S29


Pharmacokinetics solutions in patients with treatment-resistant, CYP enzyme systems, fast and slow metabolizer

Gul Eryilmaz

NPIstanbul Neuropsychiatry Hospital, Istanbul-Turkey e-mail address:

In a CYP2D6 genotyping study on Turkish psychiatric patients by Herken et al., poor metabolizer ratio has been reported as 1.45%, and ultra-rapid metabolizer 10.29%. The sum of the frequency of poor and rapid metabolizers in terms of CYP2D6 activity is about 12.7%. Hence, 12.7% of Turkish population is at risk for R treatment. In slow metabolizers, side effects of drugs occur more, while the drug ineffectiveness arises in fast metabolizers. In evaluation of CYP2D6 enzyme activity, genotyping, phenotyping by prop medication and TDM are methods that are used. Although genotyping for CYP2D6 enzyme is a very important data in terms of drug metabolism, it, alone, is not sufficient in terms of showing enzyme activity. Genotyping is recommended, if a substrate that has quite different metabolism is being used, if the drugs a have narrow therapeutic range (if it has the toxic effects due to genetic differences in metabolism), if the drug or metabolite has an unusual plasma concentration and if genetic factors thought to be responsible, if there is a chronic disorder that needs a lifelong treatment. Additionally, as the enzyme activity can be also affected by environmental factors in addition to genotyping factors, the most effective method for current enzyme activity of the individual is phenotyping.

In a phenotyping study performed with dextromethorphan metabolites ratio, Gaedigk et al. reported in 60% of cases polymorphism commonly seen in CYP2D6 and in 40% of the cases rare polymorphisms. Hence, estimating phenotype through genotyping has been insufficient in explaining phenotype. Nowadays, phenotypic research indicating this enzyme’s activity is increasing.

For the first time, in 1993, phenotypic investigation performed through deprisguin metabolic way has reported a similarity to R metabolism. In a study investigating the relationship between CYP2D6 enzyme activity and R hydroxylation, deprisguin probe was

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used and it was reported that phenotyping performed according to deprisguin metabolite and R/9-OHR rates are related and R plasma level might reflect enzyme activity. Today, most effective method for CYP2D6 enzyme phenotyping is dextromethorphan metabolism. According to this, 4 types of phenotyping—namely intermediate metabolizer (ARA), normal metabolizer (NM), fast metabolizer (HM), and slow metabolizer (YM)—was determined. In 1999, Huang et al. has investigated the relationship between DEX phenotyping and R plasma level in 6 cases for the first time, and 7-times decrease in the clearance of R in YM phenotype has been reported.

On the other hand, TDM will provide information on pharmacokinetics by showing the drug plasma concentration. A strong correlation between CYP2D6 enzyme activity and R hydroxylation has been reported. According to this, risperidone / paliperidone ratio was adopted as CYP2D6 index. If risperidone/ paliperidone ratio is 01-02 normal range >1: YM or CYP2D6 inhibition has been reported. In another study, in HM cases with risperidone/ paliperidone less than or equal to 0.1, genotyping was performed and the ratio for HM was evaluated as highly sensitive but nonspecific.

Keywords: CYP 2D6, treatment, resistant

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S29-S30


Bipolar disorder and substance use disorders comorbidity: diagnosis and management

Asli Enez Darcin

Uskudar University, NPIstanbul Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:

Bipolar disorder has a higher prevalence of substance use disorders comorbidity than any other psychiatric illness. Repeated epidemiological surveys have reported that people with bipolar disorder I and II have co-occurring substance use disorders with lifetime prevalence estimates ranging from 42% to 60%. Substance abuse may predispose to bipolar disorder and bipolar disorder may predispose to substance abuse, perhaps through self-treatment or through increased sensitivity to rewarding stimuli, or both disorders could arise from a common mechanism. Substance use in patients with bipolar disorder also contributes to excess morbidity and mortality. Bipolar patients with substance use disorders have a more severe course of mood disorder, including earlier onset, episodes that are more frequent, mixed episodes, hospitalizations and more complications, including anxiety- and stress-related disorders, aggressive behavior, legal problems, and suicide.

Limited data for pharmacological interventions to manage concurrent drug and alcohol use in patients with bipolar disorder are available. Nevertheless, in most studies, medications for managing mood symptoms did not appear to have an impact on the substance use disorder. Pharmacotherapy for comorbid substance use disorder and bipolar disorder typically involves use of mood stabilizers or/and atypical antipsychotics, antidepressants and concomitant use of a medication specifically for the substance use disorder, e.g., naltrexone, acamprosate. Valproate seems to be a good treatment choice for patients with concomitant bipolar disorder and substance use disorders, as add on medication or alone. Carbamazepine, lamotrigine and topiramate are the other promising mood stabilizers in management of this comorbidity. Among antipsychotics mostly studied second generation antipsychotics are quetiapine and aripiprazole in bipolar patients with comorbid substance use. Antidepressants can be lifesaving in patients who are at risk for suicide whether they have a co-occurring substance use disorder. Literature encourages the clinicians that are working on this field about substance oriented medications use like buprenorphine, acamprosate, naltrexone as add on treatment. But level of evidence for literature make us think that we are still far away from the best treatment approach for co-occurring substance dependence and other psychiatric disorders. The field of bipolar disorder comorbid with substance use disorders is in need of large double-blind, placebo-controlled randomized studies. The lack of evidence in this field prevents experts to make clinical recommendations for most of this frequent comorbidity of bipolar disorder and substance use disorders. Treatment should maximize the use of psychosocial interventions and prescription of first-linemedications with proven efficacy in the context of recurrent alcohol and substance abuse.

Keywords: bipolar disorder, substance use disorders, comorbidity, treatment Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S30

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Depression, bipolar disorders and thyroid functions

Ahmet Unal

Gaziantep University, Faculty of Medicine, Department of Psychiatry, Gaziantep-Turkey e-mail address:

Mood disorders are one of the most prevalent psychiatric disorders in clinical practice. Etiology of mood disorders is still not clear. There are many hypotheses about this issue. One of them is endocrine pathologies and especially thyroid disorders. The association between mood disorders and thyroid functions came from; thyroid hormones are recommended in treatment resistant mood disorders, thyroid dysfunctions may lead mood symptoms, and mood stabilizers like lithium may have some side effects on thyroid hormones. In this presentation, I will summarize the relationship between thyroid and mood disorders in the lights of accumulating literature.

Keywords: depression, bipolar disorders, thyroid

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S31


What is done for children who are either sexual abuse victims or sexual offenders?

Bengi Semerci

Bengi Semerci Institute, Istanbul-Turkey

e-mail address:

To sexually abuse a child is defined as, to have a child in an activity that would satisfy the sexual hunger of an adult or to condone such an act. Also sexual activities between two kids; when the age difference in between is of 4 years or more, and the younger child is forced or convinced to be a part of the activities that harbor sexual pleasure, are also defined as sexual abuse. For children who are a victim of sexual abuse or conduct sexual abuse, there are necessary measures to be followed other than the legal process. Generally, because the attention is focused on the crime and punishment, these procedures are overlooked and sexual offenses cause much worse problems than the damage it already creates.

In our country, some projects are pursued regarding what to do for sexual abuse victims once they report the crime. Child Protection Centers established in universities and Child Observation Centers established in state hospitals aim to collect all the procedure, from taking statements, to evaluating the victim physically and psychologically, under one roof. Afterwards, the child may be taken under protective custody. Sexual abuse is one the major traumas there are. Unfortunately, psychiatric and social follow up cannot be done regularly. Also these projects are still not widely spread and lack many important issues. After the psychiatric evaluation of the child for the report, there are no procedures regarding the healing process. The abused child’s treatment, which remains with their families, depends on the family’s request. In many cases, the victims do not get any treatment. There are no social projects monitoring sexually abused children.

Children, who conduct sexual abuse are completely irrelevant to these projects. Other than the punishment they get, these abusing children should be monitored, treated and should get necessary social support for both their and the community’s sake. These children, who offended a crime, are sent to a doctor merely to figure out whether they are suitable for the punishment. Moreover, if their situation is not an obstacle for the punishment, but the child still in need of psychiatric treatment, nothing else is offered for this person. Not enough is done regarding these sexual offenders and the projects lack a great deal regarding the evaluation, treatment, and rehabilitation of these kids. This is the main reason why the crime is repeated again and again.

Keywords: child, sexual abuse, sexual offenses

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Issues that need to be considered in forensic psychiatric evaluation and forensic psychiatric case examples

Halil Ozcan

Ataturk University, Erzurum-Turkey e-mail address:

Legal cases are situations that most specialists do not like and see them as a challenge to their practice. However, being appointed as a legal expert is almost inevitable. Therefore, legal experts and especially psychiatrists should have enough knowledge in order to evaluate the forensic cases appropriately. Psychiatrists need to be careful on certain legal issues. In this presentation, some important points that psychiatrists should be aware of, were emphasized. Mental disorders may have a course of improvement or worsening of the symptoms and might become chronic. (e.g. The criminal responsibility is effected by whether patients with schizophrenia had a psychotic episode or not at the time of crime, slight referential perceptions, or some thoughts not powerful as delusions may not be detected during psychiatric evaluation, patients with borderline personality disorders may have micro psychotic episodes effecting criminal responsibility). Patients should provide the legal expert with information about their past diagnosis and treatments, etc. If the patients withhold information, this situation can have an effect on the case process and this kind of can be misleading for the legal expert. As a general view, if the civil court asks for a detailed epicrisis without the consent of the person, this may not be provided due to it being confidential information. So the consent of the patient should be provided. If it is a criminal court, the epicrisis should be presented even without the consent of the patient. Otherwise, the judge may accuse the expert for preventing the course of justice and the expert can be sued for a compensation case). All possible information sources should be evaluated (information from the person of interest, relatives acquaintances of the person should be gathered and if necessary, social evaluation should be asked from the social services). The expert should answer all the questions of the judge or the prosecutor, otherwise the expert may be asked to give another expert opinion again. Any psychometric measurements such as electroencephalography (EEG), brain imaging (MRI, etc.) should also be written on the forensic expert opinion report. If necessary, personal and family history, personality traits, upbringing and cultural features should also be evaluated and reported. All findings and evaluation results should be discussed first and eventually evaluated on the conclusion part on forensic expert opinion report. Although legal expert is not the judge and does not give penalty, etc., but should examine the case file carefully. The report given is a forensic expert opinion, if the expert does not have a solid opinion, the patient can be referred to another expert or a medical legal institute. In the light of the existing data, if an expert opinion is not formed, this should be stated properly with its reasons.

Keywords: examination, forensic psychiatry

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S32


Benzodiazepine use is harmful

Fatih Canan

Akdeniz University, Faculty of Medicine, Department of Psychiatry, Antalya-Turkey e-mail address:

Benzodiazepines have several actions such as anxiolytic, sedative/hypnotic, muscle relaxant and anticonvulsant. They are used for a variety of conditions, particularly anxiety and insomnia. However, they have been prescribed widely and often inappropriately. Withdrawal syndrome, tolerance, and dependence are commonly known side effects of benzodiazepines. However, there are many other unwanted effects of this type of drugs that have to be kept in mind, when prescribing.

Although benzodiazepines reduce tension and aggression, they can also rarely lead to a release of aggression by reducing inhibitions in individuals with a tendency to aggressive behavior. This possible effect should be remembered when prescribing for those judged to be at risk of child abuse, or for any person with a previous history of impulsive aggressive behavior.

Drowsiness, poor concentration, ataxia, dysarthria, motor incoordination, diplopia, muscle weakness, vertigo and mental confusion caused by benzodiazepines can affect driving skills and the operation of potentially dangerous machinery.

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Among the elderly, the risk of drug interactions, psychomotor slowing, cognitive dysfunction and paradoxical disinhibition may be amplified. Benzodiazepine use in the elderly is associated with an increased rate of falls that cause hip and femur fractures. Benzodiazepines may also increase the risk for delirium.

An association has been noted between benzodiazepine use and depressive symptoms and, in some cases, the emergence of suicidal ideation. Although the mechanism of this action is unclear, benzodiazepine-related depression might occur as a physiologic result of a reduction in central monoamine activity.

Benzodiazepines cross the placenta and are classified as class D teratogens. They may lead to the development of dependence and consequent withdrawal symptoms in the fetus. Benzodiazepines are excreted in breast milk and thus are usually contraindicated in breast- feeding mothers.

In conclusion, before prescribing benzodiazepines, it is always crucial to remember possible and frequent problems related to benzodiazepine use and seek the causes of anxiety and to try to modify them.

Keywords: benzodiazepines, side effects, treatment

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S32-S3


Benzodiazepine use is useful

Murat Semiz

Gaziosmanpasa University, Faculty of Medicine, Department of Psychiatry, Tokat-Turkey e-mail address:

Benzodiazepines are the medications used to treat many of the frequent symptoms seen in medical practice and especially in psychiatry, including anxiety, depression, insomnia, epilepsy and other psychophysiological disorders. Benzodiazepines derive their name from their molecular structure. These molecules share a common effect on receptors that have been denominated benzodiazepine receptors, which modulate GABA activity. During 1980s, there was a decrease in benzodiazepine use because of their dependence and abuse potential. However, recent studies suggest that benzodiazepines are not drugs of abuse for all patients. Patients, who have a preexisting history of substance abuse or co-morbid personality disorders, are prone to addiction.

Benzodiazepines are divided into three groups according to the duration of action: 1) short-acting (triazolam, midazolam); 2) intermediate- acting (alprazolam, lorazepam); 3) long-acting (diazepam, clorazepate, clonazepam). They have a rapid anxiolytic sedative effect and are most commonly prescribed for immediate treatment of insomnia, acute anxiety and agitation or anxiety associated with any psychiatric disorder. Alprazolam and clonazepam, both high potency benzodiazepines, are commonly used medications for panic disorder. However, the selective serotonin reuptake inhibitors are also used for treatment of panic disorder. Benzodiazepines have the advantage of rapid effect and of not causing significant sexual dysfunction and weight gain. Clonazepam has been suggested to be effective treatment for social phobia. In addition, several other benzodiazepines (e.g., diazepam) have been prescribed as adjunctive medications for treatment of social phobia. Clonazepam and lorazepam are useful in the management of manic episodes and as an adjuvant to maintenance therapy in lieu of antipsychotics. Additionally, benzodiazepines are prescribed to provide sedation when changing antipsychotic medications.

In this presentation, the pharmacological properties, psychiatric use and side effects of the benzodiazepines will be reviewed based on the existing controlled studies and general principles. Additionally, minimizing the risk of withdrawal syndrome will be emphasized. Keywords: benzodiazepines, psychiatric use, side effects

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Benzodiazepine administration fields in our daily practices

Osman Yildirim

Abant Izzet Baysal University, Faculty of Medicine, Department of Psychiatry, Bolu-Turkey e-mail address:

Benzodiazepines are an important class of bioactive molecules, widely used as an anxiolytic agent. Their pharmacological actions are mediated through specific receptors located in a supramolecular complex with gamma-aminobutyric acid (GABA) receptors. Benzodiazepines enhance GABA neurotransmission, thus indirectly changing the activity of other neurotransmitters such as serotonin and noradrenaline.

Benzodiazepines are indicated for the short-term relief of anxiety that is severe, disabling, or subjecting the individual to unacceptable distress. The efficacy of benzodiazepines (particularly alprazolam – a high potency benzodiazepine-) in the treatment of panic disorder is well established. However, in generalized anxiety disorder, high drop-out rates due to adverse effects limit their effectiveness; in social phobia, little is known about their long-term affect; and they have uncertain efficacy in either acute or continuation treatment in post- traumatic stress disorder.

Apart from their frequent use in anxiety disorders, benzodiazepines are widely prescribed for acutely disturbed patients (mania, schizophrenia, agitated depression, agitation in medical conditions), addiction (alcohol and opiate withdrawal), neurological disorders (epilepsy, muscular spasm, spasticity), and antidepressant or antipsychotic-induced side effects.

Benzodiazepines are also frequently prescribed in the treatment of sleep disorders. However, they should only be used to treat insomnia when it is severe, disabling, or causing extreme distress. Only short-term (2-4 weeks) use is recommended.

Since benzodiazepines may cause dependency, withdrawal needs to be gradual; a withdrawal syndrome may occur as long as 3 weeks after stopping the drug. Benzodiazepines also adversely impair the individual’s ability to operate machinery or drive. They may also, paradoxically, cause increased aggression and hostility.

The key points for safe and effective use of benzodiazepines are, the careful selection of patients who might benefit from them, prescription of lower doses and in conjunction with an antidepressant, administration in clinical situations in which they are more likely to be beneficial, monitoring and managing their side-effects and minimizing the risk of withdrawal symptoms and relapse, mainly through tapering the dose and/or combining with effective psychological interventions.

Keywords: benzodiazepines, psychiatry

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Where are we according to benzodiazepine use prevalence in the world?

Abdullah Akpinar

Suleyman Demirel University, Faculty of Medicine, Department of Psychiatry, Isparta-Turkey e-mail address:

Benzodiazepines have become a treatment option for psychiatric disorders since 1960 upon the discovery of its sedative, anxiolytic and hypnotic effects and replaced the barbiturates previously used to obtain those effects. The main indications of benzodiazepines in the psychiatry practice are anxiety disorders, insomnia, alcohol withdrawal, dystonia associated with neuroleptics and akathisia. Their use is limited a possibility of causing impairment in daily, occupational and social functioning, criminal events (theft, harassment, aggression), accidents, fractures, injuries and deaths due to those effects. One-year prevalence of benzodiazepine use at least one time in Germany, Canada, the Netherlands, the USA, Sweden and Belgium was reported as 4-7%, 10%, 10%, 11%, 14.5% and 17.6% respectively. Benzodiazepines can be readily obtained from pharmacies without a prescription in Latin America and some Asian and African countries. It is considered that benzodiazepine use may be more common in those countries. High levels were reported, one-year prevalence of benzodiazepine use at least one time being 31.4% in Chile and monthly prevalence of use in Lebanon being 9.6%. In those studies, the rate of benzodiazepine use was found generally to be higher in females and elderly. It was reported that prescription rate of benzodiazepines among all physicians is 35-50% and it was most frequently prescribed by primary care physicians. It was stated that benzodiazepine

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prescription rate of psychiatrists was 4.7-11%. There was no community-based prevalence study regarding benzodiazepine use in Turkey. Keywords: benzodiazepine, prevalence

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S34-5


Childhood schizophrenia: early signs, diagnosis and therapeutics of the prodromal phase of childhood schizophrenia

Ozhan Yalcin

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:

Schizophrenia disrupts social and family relationships, resulting severe educational and occupational impairment, lost productivity, unemployment, physical illness, and premature mortality. Among people at “ultra high risk” of psychosis, about 22% to 40% is in transition within 12 months. Interventions that delay or prevent transition to psychosis from this prodromal syndrome could be clinically and economically important.

The common symptoms in the prodromal psychotic phase are; reduced concentration and attention, reduced drive and motivation, anergy, anhedonia, depressed mood, sleep disturbance, anxiety, social withdrawal, suspiciousness, deterioration in role functioning, irritability, suicidal ideas, somatic complaints, change in motility, change in sense of self, others or world, perceptual abnormalities, mood swings, day dreaming, somatic anxiety findings, obsessive-compulsive symptoms, sexual orientation difficulties, metaphysical occupations and overvalued ideas.

In the period of adolescence, it is difficult to determine these symptoms as prodromal signs of a developing psychosis as a result of the peculiar behavioral characteristics of this period.

Family education and psychoeducation must be well balanced and must be individualized as alerting the family and the patient may cause negative outcomes and increase the stress of the family and the patient. Above all, it is impossible to know whether the patient will experience full symptom psychosis. Intense family therapy and psychoeducation may cause significant stress leading detrimental effect on family function or atypical antipsychotic treatment may cause serious metabolic-cardiac side effects in a patient who will never experience psychotic disorder. Individualized assessment and individualized treatment is essential considering the risk-benefit analysis. Although the treatment of the prepsychotic adolescents aims to prevent transition to psychosis, it may also improve the symptoms of the prepsychotic adolescents and leads to improvement in functionality. Even if the patient will not experience full symptom psychosis, these prodromal sign and symptoms may continue for a long time and may cause serious burden on the academic, familial, occupational functionality. Treatments in the prepsychotic and prodromal phase should prevent transition to schizophrenia but also should aim to treat the present symptoms. Low doses of atypical antipsychotics, SSRI’s, mirtazapine, benzodiazepines, antihistaminics and lithium come into prominence in the symptomatic treatment of prodromal phase.

Although perospirone, aripiprazole, amisulpride, risperidone, and olanzapine have been found to be effective in treating the symptoms of the prepsychosis, it is controversial that whether second generation antipsychotics prevents transition to psychosis. In the first decade of the new millennium, SSRIs come forward for the prevention of schizophrenia in prepsychotic individuals, however in the recent years there has been little research on that possibility. As it is impossible to estimate the length of the treatment, aripiprazole and ziprasidone may be more reliable for the treatment of prepsychotic symptoms due to their low metabolic side effect profile.

As a result although there is no proven treatment for individuals in the prodromal phase of psychosis, CBT, Psychoeducation, Family education, low doses of atypical antipsychotics, SSRI’s (especially fluvoxamine), Mirtazapine, omega-3 fatty acids, may have little benefit on the symptoms of prepsychosis.

Keywords: childhood schizophrenia, prodromal phase, treatment

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S35

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S35

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Strategies for cognitive deficits in early onset schizophrenia

Mine Elagoz Yuksel

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Istanbul-Turkey e-mail address:

Early Onset Schizophrenia (EOS; onset of schizophrenia before the age of 18 years) is characterized by moderate to severe cognitive deficits, which have been linked to poor functional outcomes. Cognitive deficits in EOS patients include impairments in general cognitive abilities, attention, working memory, visio-spatial skills, verbal memory, visual memory. It is crucial to develop cognitive remediation strategies to achieve an optimal functional response in EOS. Studies were identified through searches of the Medline (PubMed) and PsycINFO databases using the terms ‘‘early onset schizophrenia’’ and ‘‘childhood onset schizophrenia’’ along with the terms ‘‘cognition’’ and ‘‘cognitive’’. This presentation will focus on impact of individual differences and comorbid diagnosis on cognitive functioning and pharmacological and non-pharmacological interventions for cognitive deficits in patients with EOS.

Keywords: early onset schizophrenia, cognition

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S36


How to manage agitation and aggression in emergency service

Kayhan Bahali

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Department of Child and Adolescent Psychiatry, Istanbul-Turkey e-mail address:

Visits of children and adolescents for mental health problems to emergency departments have increased markedly in recent years. Acute agitation and aggressive behaviors are common presentations in emergency departments and may be associated with various psychiatric and medical conditions. Diagnosing and treating the underlying medical-psychiatric conditions are essential to the management of agitation and aggressive behavior. Psychotic conditions are common causes of agitation among individuals attending to the emergency departments. This presentation will focus on the current approach for the prevention and management of agitation and aggressive behavior in children and adolescents, which is particularly related psychosis in emergency departments. The use of physical restraint and chemical restraint will be presented, and procedures for carrying out each of these interventions will be mentioned in this presentation. Keywords: adolescent, agitation, aggression, child, emergency, psychosis

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Treatment of dissociative disorder and difficulties encountered

Bahadir Bakim

Canakkale Onsekiz Mart University, Faculty of Medicine, Department of Psychiatry, Canakkale-Turkey e-mail address:

Dissociative amnesia-fugue treatment consists of gathering anamnesis from patient and family, emotional support, building trust in relationships, normalizing family relationships and activities with behavioral approach and prevention of regressive acts and talking about probable traumas, psychoeducation, providing impulse control and mood control.

Suppression of emotional experiences in depersonalization-derealization disorder considered as mental escape, psychodynamically. Probable anxiety evoking experiences should be identified, and it important that to produce attitudes of positive perception of own body and social surroundings, not catastrophic. There is no general pharmacotherapeutic approach for depersonalization-derealization disorder. Opioid receptor antagonists, SSRI + lamotrigine and clonazepam (if there is comorbid anxiety SSRI) were found beneficial. Basic treatment method of DID is intensive individual outpatient psychotherapy. It is considered short psychotherapy in long-term. Therapist must be very active during therapy. Hypnotherapeutic techniques are used additionally. Short-term hospitalization may be necessary in times of crisis. Psychotherapy of DID is work with alter personalities directly. DID therapy can be divided into four stages namely first, middle, late and after integration phases. DID treatment usually last a few years, while it may be prolonged in severe cases. Length of psychotherapy of DID depends on severity and repetitiveness of trauma and traumatic experiences in early age, rather than severity of symptomatology.

Integration may be easier in childhood then other ages. Quitting treatment is a high risk in adolescence. Treatment focused to integration might be delayed into their twenties. Patients test the therapist continuously. Anger could be observed in severe borderline dissociative personalities. If you have not basic positive emotions directed to patients, you cannot tolerate the stress of projective identification of patient. Number of alter personalities can vary from 1 to 50, average is 13. The goal of treatment is integration. It should be helped to alter personality to understand that they were parts of the person. It is important not to use ECT (It is regarded as contraindication according to some publications) to stay within the span of authority and to systematically intervene, when necessary. Group therapy may be helpful. They should be treated as possible as by outpatient without hospitalization, they can easily regress. Hospitalization should be as far as possible at short-term. If two or three of the patients in the ward were acting out simultaneously, they might be in competition for the attention of the team. They do not have privileges from other patients, and suffer the consequences of their non-admitted behavior. Hospitalization is usually for suicidal thoughts-initiatives, internal conflicts, anxiety and non-controllable behaviors. All alter personalities should be treated fairly and empathic. Empathy and relationship between alter personalities should be supported. Mood stabilization, prevention of unsafe sex, reckless driving, neglects of health, self-mutilation and suicide are the goals of initial phase of therapy. Working with traumatic material, mapping of the system, producing smooth inner conversations, accepting abuses, fusion of layers of alter personalities, and then integration are the route of therapy.

Keywords: dissociative disorder, treatment, difficulties encountered Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S37


Clinical evaluation and management of co-occurring conditions in autistic spectrum disorders

Koray Karabekiroglu

Ondokuz Mayis University, Faculty of Medicine, Department of Child and Adolescent Psychiatry, Samsun-Turkey e-mail address:

Clinical Features and Diagnosis: Autism spectrum disorders (ASD) are defined in terms of abnormalities in social and communication development in the presence of marked repetitive behavior and narrow interests. Patients with Asperger syndrome, as defined in the DSM IV, suffer from autistic social dysfunction but without mental retardation or language delay. Pervasive developmental disorder-

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not otherwise specified (PDDNOS), is reserved for patients who are within the autistic spectrum but do not meet the threshold for any of the named disorders. In DSM-V, the first two symptoms (social deficits and communication impairment) are merged into a single category of social-communication impairment, reducing the triad of autistic symptoms to a dyad of social-communication impairment and rigid restricted interests. During early childhood, children with autism are likely to present with language deficits and problems with hyperactivity; however, during adolescence, the symptoms might change to problems with relationships and with regulation of mood. In about one-fifth of children with autism, a history of regression is present. Most patients with autism suffer from intellectual disability. Genetic syndromes that have been described in children with pervasive developmental disorders (tuberous sclerosis, fragile X, Down, neurofibromatosis, Angelman, Prader-Willi, Gilles de la Tourette, Williams, etc.).

Screening and diagnostic instruments: The diagnosis of autism is based on obtaining a detailed developmental history and performing a systematic examination. Rating scales and structured interviews are commonly used to strengthen the process of clinical diagnosis, not to replace it. . The type of instruments selected depends on the time and the resources available. For example, ADI (Autism Diagnostic Interview), ADOS (Autism Diagnostic Observation Schedule), and the DISCO (Diagnostic Interview for Social and Communication Disorders), take hours to administer (3–5 hours if done properly) and require special training.

Comorbidity: Comorbid symptoms and disorders require considerable attention and become a focus for intervention and medical treatment. Problems such as hyperactivity, aggression, and self-injurious behaviors occur in up to half of children with ASD. Depressive symptoms often emerge during adolescence. In the previous comorbidity studies, nearly seventy percent of participants had at least one comorbid disorder and 40% had two or more. The most common diagnoses were anxiety disorder (41-45%), ADHD (28-31%), and oppositional defiant disorder (7-28%). Obsessive–compulsive disorder was more common in older children, and oppositional defiant disorder/ conduct disorder more prevalent in PDD-NOS. In a recent study most common comorbid psychiatric disorders were found to be attention deficit/hyperactivity disorder (ADHD) (56.2%), anxiety disorders (21.7%), mood disorders (8.1%), learning disorders (4.2%), and tic disorders (3.8%). While mood disorders were more in autism (14.4%) and Asperger (9.0%) groups, tic disorders (22.7%) and anxiety disorders (31.8%) were significantly more in Asperger group. All learning disorder and tic disorder cases were male. While anxiety disorders were more common in female ASD patients (27.4% vs. 20.2%), ADHD was more common in male patients (57.9% vs. 49.0%). This course is a brief summary of ASD in terms of clinical diagnostic features, subtypes, and comorbidity.

Keywords: autism, ASD, PDD, comorbidity, Asperger, PDD-NOS Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S37-S8


How to make differential diagnosis from depression to mania in adolescents?

Rasim Somer Diler

University of Pittsburgh, Faculty of Medicine, Department of Psychiatry, Pittsburgh-USA e-mail address:

Bipolar disorder (BP) is a familial and recurrent illness that significantly affects the child’s normal development. BP is often manifested by periods of depression during which the child has significant psychosocial problems and increased risk for suicide. Depression in youth is reported to be highly prevalent and relapsing condition that is treatable, but frequently comorbid and associated with significant morbidity and mortality, and has a high risk (20% to 40%) for switching into bipolar disorder. Studies in adults reported that bipolar depression was less recognized and treated than manic episodes despite the findings that depressive episodes and symptoms dominated the longitudinal course of BP and most suicide occurred during depression. Similar to adults, children with bipolar depression were more likely to have severe depression with suicidality, anhedonia, and hopelessness and had higher rates of comorbid disruptive behavior, anxiety, and substance use disorders, had lower Global Assessment of Functioning (GAF) scores and higher rates of hospitalization and psychiatric disorders in first-degree relatives compared to children with unipolar depression. However, most clinical studies with BP have focused on the manic phase of the illness. Depressed youth with BP are more likely to have more severe depression, greater suicidality, and higher rates of comorbidities and functional impairment relative to depressed youth with major depressive disorder (MDD or “unipolar depression”). However, it is difficult to clinically differentiate the symptoms of BP depression from those of MDD, and some children may still be in early phases of developing bipolar spectrum illness. This issue is very important because youth with BP depression may be treated with antidepressants that can precipitate an episode of mania or mixed BP symptoms. In addition, it may take up to 10 years from the initial symptoms of depression until BP is diagnosed and appropriate treatment is prescribed. Moreover, new DSM 5 introduced new “mixed features” specifier for major depressive disorder, first time identifying manic symptoms within depressive disorders spectrum. This brings the gap even more between mania and depression dichotomy. In conclusion, early differential diagnosis

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of depression and mania youth from a spectrum perspective is a key factor to enable youth to follow a normative developmental path and prevent an unrecoverable loss in their development.

Keywords: mania, depression, bipolar, mixed features, diagnosis

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How to treat adolescents with mood disorders from depression to mania?

Rasim Somer Diler

University of Pittsburgh, Faculty of Medicine, Department of Psychiatry, Pittsburgh-USA e-mail address:

Now that new DSM 5 introduced new “mixed features” specifier for major depressive disorder, first time identifying manic symptoms within depressive disorders spectrum, the view of the gap between mania and depression dichotomy needs to be replaced with mood disorders spectrum. Thus, early identification of bipolar disorder (BP) youth, especially during depression, and early identification of manic symptoms in major depression (MDD) is critical not only to improve the long-term prognosis of adolescents with mood disorders, but also to prevent inappropriate treatments. As demonstrated recently in adults, improving the accuracy of early diagnosis of BP in youth may be achieved by identifying objective neural biomarkers at an early age that are specific to BP and not common to MDD, which in turn can help identify predictors of treatment response. Treatment guidelines for BP in children and adolescents were recently developed, but the panel left out depression and agreed that there was insufficient evidence to develop a treatment algorithm for it. Several studies suggest that there were effective and well-tolerated treatment options (e.g., lithium, mood stabilizers, second-generation antipsychotics [SGA]) for manic or mixed episodes of BP in youth; however, there are no maintenance studies in depressed children and adolescents with BP and available data for depressive episode in BP is limited to few randomized and two open-label acute treatment studies in adolescents. Management of depression is very different in BP depression than in MDD: Antidepressants are widely used in MDD, but may exacerbate or induce mania and suicide in depressed BP youth. Antidepressant monotherapy is therefore contraindicated for the treatment of BP depression, and studies in depressed BP adults show that combining antidepressants with mood stabilizers may also not be effective. Furthermore, we know very little about treatment of MDD with mixed features, but those adolescents with episodic severe but short lasting manic episodes are at very high risk for developing BP over the next4-5 years. Treatment of mood disorder in adolescents should be tailored for each individual b taking into account their developmental history, family history, comorbidities, and mood disorder spectrum approach.

Keywords: mania, depression, bipolar, mixed features, treatment Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S39


Cognitive behavioral therapy for anxiety disorders in children and adolescents

Satwant Singh

Wordsworth Health Centre 19 Wordsworth Avenue, UK

e-mail address:,

This mini-workshop will focus on Kendall’s Coping Cat and Beckian’s Cognitive Behavioral Therapy for anxiety in children and adolescents. The Coping Cat is a 16 individual therapy session model involving the child and patients in the therapy. Outcome studies have supported the efficacy of Kendall’s Coping Cat treatment package. The workshop will discuss the 16 sessions and briefly address the adaptation of Beckman CBT for children and adolescents in relation to other anxiety disorders such as OCD and PTSD.

Keywords: CBT, anxiety disorders, children, adolescent

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Evaluation of academic productivity and promotion: which is the best according to what? Hirsch Index and its use in academic psychiatry

Salih Selek

Istanbul Medeniyet University, Faculty of Medicine, Department of Psychiatry Istanbul-Turkey e-mail address:

Indices like number of publications, citations, funding and awards gives an idea of one part of the productivity of academicians however, a universal metric has not been identified so far. H index is one of the publication metrics that might be used in academic productivity. In this course, definition of the several scientometric parameters including h index will be discussed. Several studies of h index as well as in academic psychiatry will be outlined. H index may be a valuable tool for academic productivity evaluation.

Keywords: H index, scientometrics, academic productivity, academic psychiatry Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S40


Learning and animal models

Arif Demirdas

Suleyman Demirel University, Faculty of Medicine, Department of Psychiatry, Isparta-Turkey e-mail address:

Learning is a quite long-term change occurring in behaviors by an individual’s experiences. In fact learning process is for not only human beings but also all organisms. That is why animal experiments and animal models are used to investigate learning process. There are behavioral, affective, cognitive and neurophysiological learning rules, which were put forward for learning. Behavioral theoreticians admit that learning improves establishing a connection between stimulus and behavior and changing behaviors via reinforcement is essential. According to cognitive hypothesis, learning is attributing a meaning to whatever takes place around an individual. Affective concepts concern problems about learning rather than nature of it. Neurophysiological education principles emphasize that the brain is a parallel processor and learning should be evaluated as a psychological event.

Experimental animal studies help us understand the physiological and psychological conditions of several diseases. Studies concerning learning and memory play a great role in explaining cognitive processes of neuropsychiatric diseases. When we have a look at the literature, experimental animal models about learning were described. These are Morris water maze, T maze or radial arm maze, novel object recognition, fear conditioning, 5-choice serial reaction time task, active avoidance and passive avoidance. In this course, ‘learning and animal models’ will be presented.

Keywords: animal models, learning

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Scientific article literateness

Orhan Dogan

Dogus University, Istanbul-Turkey e-mail address:

There are various motivations to write a scientific article: the contribution to science, to share knowledge, social benefit, spiritual satisfaction etc. To write scientific article is a duty and function of a scientist. If a scientific research is not published, it is not accepted that

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this research is completed.

After new knowledge was published, they are added to database and it is given as a scientific knowledge. The findings are shared with professional colleagues, and then it is presented to community benefit.

A scientific article identifies the results of original research, meets the criteria of valid publication, and various published report. It is necessary that the scientific article must be a basic publication but it must be a valid publication.

Scientific communication is very new rather than interpersonal communication. First scientific journals were published in France and United Kingdom, in 1655. There are nearly one hundred thousand scientific and technical journals in the world.

The articles in the first journals based on narrative style (For example, “First, I did this, and then I did that”. After Pasteur, it was considered methods section important, and it was developed the IMRAD format. The IMRAD is an abbreviation: I-Introduction, M-Methods, R-Results, A-and, D-Discussion. The IMRAD format is the most common approach.

A scientific article includes the sections of heading of article, abstract, introduction, methods, results, discussion, suggestions, and references.

The heading of article must be showed the content of article, it must be short, and the abbreviations must not be.

In general, abstract is on the IMRAD format. It must be written clean and spare. In an abstract, p value and abbreviation were not used. Uncertain expressions must be avoided. It must be included key words.

In the introduction section, the subject of research, the necessity of this research, the previous studies regarding subject, the missing aspects of subject, contribution of research must take place.

In the methods section, the characteristics of research, sampling, used tools, statistical assessment and ethical aspects must be written. It must be stated that how is done this research as detailed.

In the results section, the data must be selected and presented. Data must be showed in a tabulated and/or graphical form. Data must not be shown both in table and in text.

In the discussion section, the results must be repeated, but discussed. The results compared with the results of previous researches. Discussion must be only based on the data, must be avoided from speculations. The limitations of research must be stated. This section is completed with a paragraph that stated the importance of this research.

The suggestions section must be depended on results of research, and realistic and applicable.

The references section must be arranged according to rules of journal.

Similarly, the reading of scientific article will also examined and given examples.

Keywords: scientific article, IMRAD, basic publication, valid publication

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Psychotropic drug interactions

Hulya Guveli

Istanbul University, Institute of Oncology, Department of Psychosocial Oncology, Istanbul-Turkey e-mail address:

Drug interactions occur, when the effect and/or the metabolism of a drug is altered by another drug or substance. A drug interaction can be beneficial, damaging, or have no significant effect. The majorities of drug interactions have minor clinical significance but sometimes can result in potentially hazardous, and occasionally lethal adverse events. Drug interactions can be classified as pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions occur when a drug modifies the absorption, distribution, metabolism or excretion of another co-administered drug. These interactions are mainly a result of inhibition or induction of the cytochrome P450 (CYP450) isozymes. Pharmacodynamic interactions occur when the concurrent use of two drugs results in an alteration of the therapeutic and/or toxic effects of either drug without altering their pharmacokinetics, and can be additive, synergistic or antagonistic. The pharmacokinetics of a drug defines its potential for drug-drug interactions. Most drug interactions with psychotropics are pharmacokinetic and include the CYP450 family of enzymes. Drug interactions with psychotropics can cause adverse effects due to inhibition of CYP450 enzyme or can reduce therapeutic efficacy duo to induction of CYP450 enzyme. There is also a large inter-individual variation in the amount of isoenzymes that individuals possess; different individuals can be poor metabolizers or ultrafast metabolizers with respect to particular CYP450 enzymes. However, not all drug-drug interactions via the CYP enzyme system are of clinical significance. Additionally, a clinician must consider significant other factors to the patients. Younger people tend to metabolize drugs faster than older people, men faster than women. Comorbid medical conditions and gene polymorphism may also affect drug metabolism. Dose reductions in special populations may be

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necessary when the factors affecting plasma clearance are present. Assessment of the pharmacodynamic and pharmacokinetic profile of psychotropic and other drugs can help determine the clinical significance of any interactions and prevent the serious consequences of drug interactions.

Keywords: drug interactions, psychotropic agent, cytochrome P450

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Psychotropic drug use in pregnancy and lactation

Mine Ozkan

Istanbul University, Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey e-mail address:

Psychiatric disease in the pregnant or breastfeeding woman presents a significant challenge. Untreated mental illness during pregnancy carries unfavorable impression for the mother, the child, the mother–child relationship and the family. Risks to the mother include self- harm/suicide, self-neglect and reduced compliance with pre and post-natal care. Fetal underdevelopment, evidenced by low birth weight and small head circumference, is associated with antenatal maternal depression and anxiety. Short and long term consequences to the child may arise, including impaired bonding and attachment, cognitive disturbances, emotional problems and behavioral abnormalities. On the contrary treating the mother with psychotropic agents carries the risks of teratogenicity, toxicity and possible long-term neurobehavioral problems for fetus. Maternal medication during the first trimester of pregnancy, particularly between the third and eighth weeks of gestation, is most relevant with regard to morphological teratogenesis, whilst that during the second and third trimesters may have deleterious effects on growth and/or functional development and toxic effects.

Clinical management is complex, involving competing risks to mother and offspring; the challenge lies in effectively treating mental illness, whilst minimizing exposure of the child to harmful medication. Several factors must be considered, including possible teratogenic effects of medication, the safety of medication during labor and delivery, possible long-term neurobehavioral effects and the effects of ongoing exposure during breast feeding. In the already pregnant women, the opportunity to reduce the dose of medication with a view to a (relatively) drug-free first trimester is often lost. Indeed by the time of presentation, pregnancy is often well progressed, with resultant exposure of the unborn child to potentially teratogenic medication. Maternal risks associated with drug withdrawal or reduction may predispose the unborn or breast-feeding child to more harm than the drugs themselves, mandating continued pharmacotherapy. No drug is absolutely safe; indeed the FDA has not approved any psychotropic medication for use during pregnancy or lactation.

The clinician faced with the pregnant or breastfeeding woman therefore requires to undertake a risk-benefit assessment, tailored to the individual patient, with regard to the continuance or commencement of psychotropic medication. Relevant issues in such an analysis include the severity of the underlying psychiatric disorder, the consequences of leaving it untreated, potential adverse effects of medication on both mother and child, and the stage of pregnancy/ breastfeeding. Treatment options and their risks and benefits should be discussed with the patient and caregivers, and the possibility of delaying medication until the second trimester may be considered. Non-pharmacological interventions in the form of individual or group psychotherapy and enhanced psychosocial support should be considered before prescribing medications, particularly if the patient has mild symptoms or is in the early stages of pregnancy. If treatment is deemed appropriate, the smallest number of medications at the lowest possible dose consistent with control of the mental illness should be prescribed.

Keywords: psychotropic drug, pregnancy, lactation

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Pharmacotherapy principles in consultation-liaison psychiatry

Sedat Ozkan

Istanbul University, Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey e-mail address:

Consultation-liaison psychiatry is the subspecialty of psychiatry concerned with medically and surgically ill patients. The consultant needs to have knowledge of psychotherapeutic and psychopharmacological interventions as well as knowledge of the wide array of medicolegal aspects of psychiatric and medical illness and hospitalization. Psychopharmacological interventions are an essential part of the management of the medically ill. Numerous physical conditions may cause, exacerbate or first present themselves as psychiatric syndromes, and appropriate use of psychopharmacology necessitates a careful consideration of the underlying medical illness, drug interactions, and contra indications. In addition, many medications used in the treatment of medical/surgical illness are associated with psychiatric syndromes. Therefore, the consultant must be knowledgeable about the psychiatric effects of medications as well as the specific indications for psychopharmacological interventions. Pharmacotherapy of the medically ill often involves modification in dosage (e.g., to account for older patients with an increased volume of distribution, a decreased rate of metabolism, and an increased physiologic reactivity). Furthermore, modifications may be necessary because of liver, kidney, or cardiac disease, or because of potential for multiple drug–drug interactions. Pregnancy presents another challenge, with concerns regarding potential teratogenicity.

Keywords: pharmacotherapy, consultation-liaison psychiatry Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S43


Psychotropic drug use in liver and renal failures

Serap Oflaz

Istanbul University, Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey e-mail address:

Liver or renal failures are common medical conditions, and many patients have comorbid psychiatric disorders. Liver and kidney have significant roles in the pharmacokinetics of drugs including the mechanisms of absorption, distribution, metabolism or excretion. The liver is the primary site for metabolism of psychotropic drugs. The processing and elimination of drugs from the body occurs through two phases of metabolism: phase 1 reactions, during which CYP 450 enzymes convert the parent compound to metabolites through processes of oxidation, reduction, or hydrolysis and phase two reactions, which couple the metabolites with endogenous substances rendering them more water-soluble for excretion from the body. Regarding antidepressant metabolism, the CYP 2D6 and CYP 3A4 systems may be the two most important metabolic pathways, as most psychotropic drugs are eliminated via these pathways.

Liver failure affects basic elements of medication pharmacokinetics, from absorption to metabolism, distribution to elimination, changing drug levels, duration of action, and efficacy. Additionally, physiological models of hepatic drug elimination have emphasized the importance of physiological variables such as hepatic blood flow, protein binding and intrinsic clearance of the liver on hepatic drug elimination. Dose adjustment of psychotropic drugs in patients with liver disease may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. Following the administration of a drug to a patient with hepatic impairment, careful monitoring of the patient and also monitoring of plasma or blood drug concentrations remain important considerations.

The kidney is a primary route of drug elimination; abnormal kidney function is predicted to alter the pharmacokinetics of agents metabolized and/or excreted predominantly through this route. In renal failure, there is a general slowing of chemical reduction and of hydrolysis, but there are normal rates of glucuronidation, microsomal oxidation, and sulfate conjugation. Drug metabolites that are pharmacologically active may be retained in patients with renal insufficiency and may cause adverse effects. Very few drugs are excreted from the body unchanged in the urine; most are metabolized within the body to less lipid-soluble compounds that are excreted by the kidneys. So that few drugs are contraindicated with end stage organ dysfunction, but many require dose adjustment and caution. Guiding principles include, but are not limited to, slow titration of doses, low-dose treatment initiation, and careful monitoring of clinical response.

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Psychiatric consultants need to be aware of the presence of comorbid renal, liver and psychiatric disorders, and they should be knowledgeable about the use of psychotropic medications in this situation. Disease-related changes in pharmacokinetics and pharmacodynamics, as well as vulnerability to side effects, polypharmacy, and potential drug interactions are all important considerations. Keywords: psychotropic drug, liver, renal failure

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Current data and approaches related to treatment of childhood-onset schizophrenia

Gul Karacetin

Bakirkoy Prof. Dr. Mazhar Osman Research and Training Hospital, Department of Child and Adolescent Psychiatry, Istanbul-Turkey e-mail address:

Early onset schizophrenia is defined as the onset of psychosis before the age of 18 years and very early-onset schizophrenia is a term used for cases developing before the age of 13 years. The aim of this presentation is to review the recent studies related to treatment of childhood-onset schizophrenia.

A computerized-aided literature search was performed in PubMed database for recent studies that assessed the effectiveness, safety and tolerability of first-generation and second- and third-generation antipsychotics in children and adolescents with schizophrenia.

The main treatment modality in schizophrenia is pharmacological in both children and adults. Antipsychotic drugs are the first-line of treatment and atypical antipsychotics should be preferred to typical antipsychotics as they show at least the same efficacy and a better tolerability in childhood-onset schizophrenia. Recent randomized controlled trials have shown the efficacy of some atypical antipsychotics in childhood-onset schizophrenia. As a result, aripiprazole, olanzapine, quetiapine, paliperidone and risperidone have received formal indications for the treatment of schizophrenia between the ages of 13-17 years. The pediatric use of atypical antipsychotic drugs has increased considerably over the past decade. Risperidone was the most often prescribed atypical antipsychotic in a naturalistic longitudinal study of early-onset first psychotic episodes in children and adolescents, followed by quetiapine and olanzapine. Clozapine, which is the prototype of the atypical antipsychotic class, is reserved for cases unresponsive or intolerant of other antipsychotics because of the risk of serious side effects. Risperidone is associated with a higher frequency of extrapyramidal symptoms than other antipsychotics, while olanzapine is associated with marked weight gain. Hyperprolactinemia and QTc interval prolongation are the other side effects that raise concern for the clinical use of antipsychotics in children and adolescents.

Early detection and treatment of childhood-onset schizophrenia may improve outcomes of the disorder. Current data provides evidence for the effectiveness and safety of atypical antipsychotic use in children and adolescents with schizophrenia. Although atypical antipsychotics are associated with a lower risk of extrapyramidal symptoms, metabolic abnormalities such as weight gain, hyperglycemia and dyslipidemia require careful monitoring in children and adolescents. Antipsychotic drugs may also differ with regard to their pharmacokinetics, which should be kept in mind for improving utilization of these drugs in children and adolescents.

Keywords: adolescents, children, effectiveness, safety, schizophrenia Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S44

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Drug interactions in psychopharmacology Dursun Karaman

Gulhane Military Medical Academy, Department of Child and Adolescent Psychiatry, Ankara-Turkey e-mail address:

Modifications in the effect of a drug are caused by differences in the absorption, transport, distribution, metabolization or excretion of one or both of the drugs compared with the expected behavior of each drug when taken individually. These changes are basically, the modifications in the concentration of the drugs.

Inhibition: Fluvoxamine inhibits CYP 1A2 and the serum level of theophylline increases. Induction: Carbamazepine and phenobarbital induce cytochrome P450 enzymes and eventually the metabolism of TSA increases.

Treatment of ADHD in case of epilepsy comorbidity:

Dexamphetamine may be preferred to methylphenidate for children with both ADHD and epilepsy. Although children with ADHD are increasingly recognized as being at an elevated risk for seizures, treatment of ADHD symptoms with atomoxetine does not appear to elevate this risk further. The shared vulnerability between ADHD and seizure activity should be taken into account when making treatment decisions for populations of children with epilepsy and children with ADHD. No interactions with any of the AEDs have been reported for atomoxetine, while MPH can increase phenytoin serum concentrations. Furthermore, MPH serum concentrations may be lowered by the contemporary administration of carbamazepine, thus leading to a loss of efficacy.

Keywords: drug, interaction, child

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Psychotropic drug-drug interactions; two cases from the clinical practice

Meryem Ozlem Kutuk

Malatya State Hospital, Department of Child and Adolescent Psychiatry, Malatya-Turkey e-mail address:

A drug interaction, defined as the modification of the action of one drug by another, can be beneficial or harmful, or it can have no important effect.

An acknowledgment of drug interactions at the clinics is becoming increasingly necessary with the rising use of combinations of drugs in all medical conditions.

Drug interactions are usually classified as pharmaceutical, pharmacodynamic and pharmacokinetic. Of the three mechanisms, pharmaceutical interactions are least likely to lead to problems in clinical practice and there are no potentially risky interactions of this type with psychotropic drugs. Pharmacokinetic interactions occur when the absorption, distribution or elimination of one drug is influenced by another.

The most common interactions seen in clinical practice are pharmacodynamic. They occur when drugs compete for the same receptor or produce antagonistic or synergistic effects on the same target organ or system. The most important enzymes involved in drug interactions are members of the cytochrome P450 (CYP) system that are responsible for many of the phase 1 biotransformations of drugs. The other potential for interactions involving uridine diphosphate glucuronosyl transferases (UGT) responsible for phase two conjugation reactions, is newly recognized very well. Many psychotropic drugs have a high affinity for one or more of the enzymes in the CYP or UGT systems, which play a major role in their metabolism. Any attempt to keep hundreds of potential drug interactions in mind to prevent hazardous interactions is ineffective. Rather, a child psychiatrist should have a basic understanding of the types and timing of possible drug interactions and then develop prevention strategies in prescribing psychotropics. Additionally, drug interaction simulation software that detail both reported and predicted CYP- based, glucuronidation-based and other drug interactions are emerging to be part of a clinician armamentarium. Finally, two cases will be discussed about this topic in this section.

Keywords: psychotropic drug interactions, P450 (CYP) system, adverse events Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S45

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Psychotropic drug interactions with non-psychotropic medications

Sevcan Karakoc Demirkaya

Erenkoy Mental Health and Neurology Training & Research Hospital, Department of Child and Adolescent Psychiatry, Istanbul-Turkey e-mail address:

A drug interaction occurs when the effectiveness or toxicity of a drug is modified by the addition of another drug. Sometimes, drug interactions may be beneficial, leading to increased efficacy or reduced risk of side effects. However, more often, drug interactions are important when concurrent drug administration leads to decrease in efficacy or increase in toxicity of medications. Drug-drug interactions occur via two ways; pharmacodynamic and pharmacokinetic interactions. Pharmacodynamic interactions mean synergy or antagonism of each drug’s effects at target receptors. Pharmacokinetic drug-drug interactions may occur by mechanisms, including alterations in drug metabolism, absorption, excretion, and distribution. In pharmacokinetic interactions, blood level of administered drug changes.

Many psychotropic drugs have significant interactions with other medications. Psychotropic drugs are mostly metabolized in the liver by cytochrome P450 (CYP) enzymes. Therefore, they are sensitive to metabolically based drug interactions. Psychotropic drug-drug interaction may occur with other psychotropic medications as well as with agents used for the treatment of accompanying somatic illnesses. P450 inhibitors produce an increase in blood levels of drugs, which are metabolized by CYP enzymes. Conversely, inducers cause an increase in metabolization and decrease in blood levels. Enzymatic inhibition is usually immediate, whereas induction requires several days to two or more weeks to show an effect on drug metabolism. In child psychiatry practice, antipsychotics (especially risperidone, aripiprazole and olanzapine), selective serotonin reuptake inhibitors (fluoxetine, sertraline, and escitalopram), tricyclic antidepressants (imipramine), methylphenidate and atomoxetine are mostly prescribed. CYP2D6, CYP3A4 and CYP2C9 are commonly involved in psychotropic metabolism. Therefore, other drugs prescribed for somatic diseases altering CYP enzymes can change psychotropic drug levels.

In summary, risperidone is metabolized primarily by CYP2D6 and, to a lesser extent, CYP3A4. Aripiprazole is metabolized by CYP2D6 and CYP3A4. Fluoxetine and paroxetine are potent inhibitors of CYP2D6; sertraline inhibits CYP3A4. Stimulants react with other drugs through pharmacodynamic reactions. Dopaminergic, noradrenergic and possible serotonergic receptors play role in stimulant and other drug interactions. Atomoxetine does not alter CYP enzymes but drugs affecting on CYP2D6 can cause differences in atomoxetine metabolism. Carbamazepine stimulates many enzymes especially CYP3A4 and leads to many important alterations. It is essential to be aware of any drug, prescription or otherwise, that the patient may be taking concurrently and to evaluate the potential interaction. As part of medical history, enquiries should be made about all medications, including those prescribed by other physicians; over-the- counter drugs (Aspirin, painkiller); dietary supplements (ginseng, grapefruit juice); and herbal preparations (St John’s worth) and alcohol use. Drugs used for common childhood disorders such as asthma (theophylline, beta agonists), infections (erythromycin), epilepsy (e.g. carbamazepine, phenytoin), fungal infections (e.g. fluconazole), nasal congestion (pseudoephedrine) can cause drug-drug interactions with psychotropics. Therefore, clinicians must be careful in clinical practice Two case scenario about psychotropic drug interactions with non-psychotropic medications will be discussed in the presentation.

Keywords: psychotropic drugs, CYP enzymes, drug interactions Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S46


An adolescent with obsessive compulsive disorder and bipolar disorder: A case report

Esra Cop

Yenimahalle State Hospital, Ankara-Turkey

e-mail address:

One to three percent of children and adolescents have obsessive-compulsive disorder (OCD). Although high co-morbidity occurs between OCD and Bipolar Disorder (BD) in adults, there has been limited research on anxiety in pediatric BD.

A 15 year-old adolescent on chlorpromazine treatment for OCD was referred for his manic symptoms. During hospitalization, chlorpromazine was discontinued. Lithium 20 mg/kg was initiated gradually. Manic symptoms were recovered in one month. Aripiprazole and clonazepam treatment was combined with cognitive behavioral therapy for his OCD symptoms. He was discharged after 2 months

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with partial remission of OCD symptoms.

This OCD case will be discussed as a severe case with comorbid BD having complicated treatment approach. Keywords: adolescent, obsessive compulsive disorder, bipolar disorder, comorbidity.

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Impairments in social skills in attention-deficit hyperactivity disorder: a case report

Ayse Burcu Ayaz

Sakarya UniversityTraining and Research Hospital, Department of Child and Adolescent Psychiatry Clinic, Sakarya-Turkey e-mail address:

In Attention-Deficit/Hyperactivity Disorder (ADHD), the symptoms of attention deficit, hyperactivity and impulsivity occur and it is thought that this disorder influences the school age children at the rate of 3-5% throughout the world. ADHS leads to loss of functioning in cognitive, academic, family and professional areas. Another area impaired in ADHS is social functioning. Impairment in social functionality mostly emerges in the form of refusal by peers and having conflicts with other children and adults. In addition, impairment in social functioning is important for short and long-term unfavorable prognosis of ADHD.

5 year old boy were referred to a child and adolescent psychiatry clinic in 2009 with the symptoms of hyperactivity, temper tantrums, acting as the opposite sex, and impairments in social skills. He was assessed by a semi-structured interview based on DSM-IV criteria, and diagnosed as ADHD-combined subtype. The impairments in social functioning and the treatment modalities between 2009 and 2014 will be discussed in this section.

The implementation of interventional programs in the involved areas such as early social skill training for preventing impairment in social functioning may help to alleviate the effect of disorder in adulthood. The efficiency of family training, judicious drug treatment and intervention programs should be increased. In interventions, comorbid disorders as well as ADHD should be taken into account and if necessary, supplementary treatment directed to these disorders should be added to the program.

Keywords: attention deficit disorder with hyperactivity, child, social problems Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S47


Comorbidity between obesity and diagnosed attention deficit hyperactivity disorder in children and adolescents: case report

Arzu Onal

Maslak Acıbadem Hospital, Istanbul-Turkey

e-mail address:,

Obesity is now reaching epidemic proportions in the pediatric population worldwide. Previous studies have reported associations between child overweight and some features of psychopathology as depressive symptoms, attention-deficit/hyperactivity disorder, and low self-esteem.

Attention-Deficit/Hyperactivity Disorder is one of the most common psychiatric disorder which affects 5-10% of school age children worldwide. Although somewhat overlooked in the past, in recent years studies have focused on the relationship between ADHD and obesity.

A 12-year-old male patient was referred to a child endocrinology outpatient clinic with his parents because of obesity complaint. The patient, who was diagnosed as having probable ADHD after the evaluation of the questionnaire filled out by his parents, was invited to the child and adolescent psychiatry outpatient clinic for further evaluation. ADHD was determined according to DSM-IV diagnostic criteria, information obtained from his parents and teacher. Additionally, sociodemographic form, the Conners Parents Rating Scale and Strengths and Difficulties Questionnaire (SDQ) were administered.

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S47

Scientific Program Abstracts

Understanding the underlying pathological mechanisms would highlight the relation between ADHD and obesity could be beneficial about treatment and managing outcomes.

Keywords: attention, hyperactivity, obesity

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S47-S8


Psychotropic drug interactions in systemic disorders of children and adolescents

Tayyib Kadak

Istanbul University, Cerrahpasa Faculty of Medicine, Department of Child and Adolescent Psychiatry, Istanbul-Turkey e-mail address:

Psychiatric morbidity in chronic childhood illnesses is higher than general population ranging with 10–30%. Risk factors for morbidity are multiple admissions to hospital, adaptation to illness, physical disability, brain dysfunction, pain frequency, younger age, poverty, single parent family and increased psychological symptoms in the parents. In psychiatric consultation, patients receive psychotropic medication for broad-ranging diagnoses, including depression, anxiety, delirium, behavioral disturbances, and substance abuse and withdrawal. Potential for specific drug-disease and drug-drug interactions is enormous.

The appropriate use of psychopharmacology in medically ill patients requires consideration of the underlying medical illness, potential alterations to pharmacokinetics and pharmacodynamics, drug–drug interactions, and contra indications. By recognition of these issues, there must be great consideration about the prescription, safety, and efficacy of psychopharmacological treatments in medically ill patients.

Physical disease and organ failure can interfere with drug absorption, distribution, metabolism, and elimination. A physical condition and malfunction organ can also influence a variety of different aspects of drug handling. Therefore, these conditions are important in choosing and managing psychoactive medications. Psychopharmacological agents need monitoring and modifying drug dose or administration in seriously ill patients.

While most psychoactive drugs are primarily subject to hepatic metabolism, hepatic disease or failure, mostly, challenges treatment of psychiatric disorder. Using drugs in patients with renal impairment needs careful consideration especially lithium. Moreover, medical conditions related with cardiovascular disease (congestive heart failure, cardiac conduction abnormalities, etc.), pulmonary disease and respiratory disorders (hypoxia and hypercarbia, cystic fibrosis), gastrointestinal disease (mucosal integrity or gut motility, lumen pH) and endocrine disease affect pharmacokinetic and pharmacodynamic properties of drug. We will discuss these drug-disease interactions with case illustrations in systemic disorders.

Keywords: drug-interaction, systemic disorder, psychopharmacology Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S48

S48 Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 –



Polypharmacy is a need in psychiatric practice

Mesut Cetin

Gulhane Military Medical Academy, Haydarpasa Training Hospital, Department of Psychiatry, Istanbul-Turkey e-mail address:

Polypharmacy is defined as using two or more drugs in treatment of one disorder. It might be considered as a “rule” rather than “exception” in psychiatry. The National Association of State Mental Health Program Directors (NASMHPD) categorized polypharmacy as follows in 2001 NASMHPD Technical Report: “same class polypharmacy,” such as using two SSRIs in a case of depression; “multi-class polypharmacy” (e.g. use of a mood stabilizer like valproate along with an atypical antipsychotic, such as olanzapine, for treatment of mania); “adjunctive polypharmacy” (e.g. treating insomnia caused by bupropion with trazodone); “augmentation polypharmacy” refers to the use of one medication at a lower than normal dose along with another medication from a different class in full therapeutic dose for the same symptom cluster (e.g. addition of low dose haloperidol in a patient responding to risperidone alone only partially); or addition of a medication that would not be used alone for the same symptom cluster (e.g. augmentation of antidepressants with lithium or thyroid hormone), and finally “total polypharmacy” which means using more than two medications in the identical pharmacological category for the same condition at the same time.

Polypharmacy has become a common clinical practice for many psychiatric conditions. Up to one-third of the patients visiting outpatient psychiatry clinics have been found to be on three or more psychotropic medications.

Polypharmacy could increase medical risks (adverse effects, drug and food-interactions, morbidity, mortality, etc. ) and decrease quality of lives of the patients receiving it. Polypharmacy should be considered only after monotherapy has been tried and failed. It should also be based on evidence (when available) in addition to knowledge of mechanisms of action, pharmacodynamics, and pharmacokinetics of medications and should always keep the risk versus benefit ratio in perspective.

At times polypharmacy is applied based on anecdotal or personal clinical experience, which would be non-scientific and risky, but it should be rational and valid based on good evidence such as adding lithium in a treatment resistant depression case, which has been proven to be effective in several double blind controlled studies. When rational polypharmacy can address treatment resistance, then quality of life of the patients would be improved. However, irrational use of polypharmacy in practice poses very serious risks even death and might result in irreversible damage or morbidity to our patients. Moreover, irrational polypharmacy practices also wastes limited resources, can increase pharmacoeconomic costs, and may result in lawsuits.

The principles of rational polypharmacy should be built on a solid knowledge and training on psychiatry and psychopharmacology. In addition, clinicians should update their knowledge, clinical skills, and abilities regularly by attending to psychopharmacology lectures, conferences, workshops, courses, etc. delivered by experts in their field throughout their careers.

Keywords: psychotropics, polypharmacy, monotherapy, concurrent medication use

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S49


Abstinence should be the goal in the treatment of alcohol use disorder

Ilhan Yargic

Istanbul University, Istanbul Faculty of Medicine, Department of Psychiatry, Istanbul-Turkey e-mail address:

A debate about the possibility to return to controlled drinking in the treatment of alcoholism is implemented until 1960s in the addiction field. USA is dominated by those, who consider abstinence as the appropriate goal while service providers in UK favor controlled drinking. It is important to remember that problem drinking is not a single entity. It ranges from hazardous (or risky) drinking to alcohol use disorder of various severities. The definition of alcoholism is very critical in this debate. For example, according to the Alcoholics Anonymous (AA), anyone who can recover by drinking moderately, was not an alcoholic at the beginning.

Among those who consume alcohol, there is a wide spectrum of alcohol consumption. National Institute on Alcohol Abuse and

Scientific Program Abstracts

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S49

Scientific Program Abstracts

Alcoholism (NIAAA) recommends that adult men should not exceed four standard drinks of alcohol per day and women no more than three drinks. Below this level, alcohol consumption has a ‘low risk’ in terms of health or social harms. NIAAA advices to drink less than 14 standard drinks of alcohol per week in men and 7 standard drinks in women. Those people who drink above these limits but have not experienced negative consequences related to alcohol are regarded as hazardous (or risky) drinkers, because the level of their drinking increases the risk of harm in the future. But this group of people is not included in alcohol use disorder category.

Alcohol dependence syndrome or alcoholism, which is a part of alcohol use disorder, includes a craving to take alcohol, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to alcohol use than to other activities, increased tolerance, and sometimes a physical withdrawal state. Alcohol use disorder exists on a continuum of severity. It can be subdivided into categories of mild, moderate and severe.

In the general population, there is substantial remission from alcohol use disorders over time most of which takes place without any contact with alcohol treatment services. Although many young people who meet the criteria for alcohol use disorder in their 20s remit before their 40s, those who are still alcohol dependent in their 40s tend to stay that way. People typically enter specific alcohol treatment at this age period. People, who go under alcoholism treatment, are usually more severely ill and have more common psychiatric and medical comorbidities compared to nonclinical heavy drinkers. Most studies about treatment outcome of alcohol use disorder find that 70 to 80% relapse in the year following treatment

Hazardous (risky) drinkers may respond to a brief intervention without any further need for specialist treatment. In other words, for people who have not yet developed alcohol use disorder, but are in danger of crossing the line into it may benefit from moderation management. However, true alcohol use disorder patients need treatment services to assist the individual to stop drinking alcohol. It has been reported that clients, who initially stated that they preferred to get abstinent showed a better outcome than those who preferred a non-abstinent goal in treatment. This superior outcome was clearer at 3 months’ follow-up but still evident at 12 months’ follow-up

At the initial stages of treatment, patients may be ambivalent or resistant to changing their drinking behavior or dealing with their problems. At this stage, an approach that may increase the patient’s motivation towards engagement with treatment is helpful. The clinician may set goals for moderate drinking for a patient who is still in denial of his inability to control drinking so that the patient may be convinced to go further in treatment. For most people who are alcohol dependent the most appropriate goal in treatment is complete abstinence. The higher the level of alcohol dependence, the lower the chance of returning to moderate or ‘controlled’ drinking. Further, for people with significant psychiatric or physical comorbidity, abstinence is the appropriate goal. If a patient asks for moderation but the clinician considers that it is risky, the clinician should give a strong advice that abstinence is most appropriate to prevent medico-legal problems.

Keywords: alcoholism, dependence, abuse, abstinence, controlled drinking, moderation Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S49-S50

S50 Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 –

Scientific Program Abstracts



Metabolic side effects of psychotropic drugs

Harold Carlson

Stony Brook University, Stony Brook, NY, USA

e-mail address:

Psychotropic drugs may have a variety of endocrine and metabolic side effects which may be harmful to patients, and which may lead to poor compliance with their medication regimen.

Lithium may inhibit thyroid function, particularly when given in combination with valproate, carbamazepine or quetiapine. Thyroid function tests should be periodically monitored in patients taking lithium, and thyroid hormone replacement therapy given if hypothyroidism develops.

Children taking stimulants or atomoxetine for ADHD may have anorexia and a resulting slowing of growth. Efforts to increase caloric intake, along with drug holidays, may be needed to counteract this tendency.

Several antipsychotic medications elevate serum prolactin, which may result in hypogonadism. Switching to a prolactin-sparing antipsychotic medication may be helpful; alternatively, addition of aripiprazole (an antipsychotic with partial dopamine agonist activity) to the patient’s regimen may correct the hyperprolactinemia.

Atypical antipsychotics may produce insulin resistance, weight gain, hyperglycemia and hyperlipidemia. Switching to a more metabolically neutral drug may be beneficial, or initiation of weight loss programs or medications may help.

Finally, valproate has been shown to lead to the development of the polycystic ovary syndrome in young women. Monitoring the patient’s menstrual history is necessary to detect this condition. Choosing a different mood stabilizer is helpful, and use of an oral contraceptive may avoid the development of menstrual irregularity and hirsutism in patients taking valproate.

Keywords: metabolic side effects, psychotropic drugs

Bulletin of Clinical Psychopharmacology 2014;24(Suppl. 1):S51

Bulletin of Clinical Psychopharmacology, Vol: 24, Supplement: 1, 2014 – S51

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