“Psychia

Dear Reader,

It gives us immense pleasure to share the April’ 2023; issue 67 of “Psychia Tree”, which explores the clinical

evidence supporting the new understandings and happenings in the field of Psychiatry

Being a healthcare custodian of the society, clinicians are constantly thriving to be abreast with the novel understandings of disease and its management. In this context, this is our initiative to provide you a compiled and to the point information. Present booklet comprises of recent and latest deeds in the field of psychiatric disorders like depression, anxiety disorder, schizophrenia, bipolar disorder etc. and their management.

We hope that it will facilitate increased cooperation and innovation and enthuse commitment to prevent these disorders and providing the best possible care for people who suffer from these conditions.

Table of Content

S. No.

Content

Page No

Depression in Major Neurodegenerative Diseases and Strokes

Depressive Symptoms and Risk of Acute Stroke: INTERSTROKE Case-Control Study

Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder

Successful high dose antipsychotic treatment with cariprazine in patients on the schizophrenia spectrum

Depression Is Associated with an Increased Risk of Subsequent Cancer Diagnosis

The relationship between moral judgment ability, parenting style, and perfectionism in obsessive- compulsive disorder patients

Antipsychotic-related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth

Clinical outcomes of recommended active pharmacotherapy agents from NICE guideline for post- traumatic stress disorder

Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression

Safety and effectiveness of vortioxetine for major depressive disorder

Table of Content

S. No.

Content

Page No

Effects of vortioxetine on cognition and fatigue in patients with multiple sclerosis and depression

Pharmacological Strategies for Bipolar Disorders in Acute Phases and Chronic management

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression

Combining Ketamine and Psychotherapy for the Treatment of Posttraumatic Stress Disorder

Triggers for acute mood episodes in bipolar disorder: systematic review

Real-world effectiveness of mood stabilizer use in schizophrenia

Important day and conference

Depression in Major Neurodegenerative Diseases and Strokes

• Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient’s disability and quality of life.

• The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability.

Brain Sci. 2023 Feb 13;13(2):318.

The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable.

Depressive Symptoms and Risk of Acute Stroke: INTERSTROKE Case-Control Study

• In the INTERSTROKE study, explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type

• Results of 26,877 participants, 40.4% were women, the mean age was 61.7 ± 13.4 years.

• The prevalence of depressive symptoms within the last 12 months was higher in cases compared to controls (18.3%vs.14.1%,p < 0.001)

• In multivariable analyses pre-stroke depressive symptoms were associated with greater odds of acute stroke, which was significant for both intracerebral hemorrhage and ischemic stroke.

• A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms.

In this global study we recorded that depressive symptoms are an important risk factor for acute stroke, including both ischemic and hemorrhagic stroke

Neurology. 2023 Mar 8:10.1212/WNL.0000000000207093.

Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder

• Both studies were 52-week, open-label, flexible-dose extension studies to evaluate the safety and efficacy of vortioxetine in adult patients with MDD following prior double-blind studies.

• Patients in the first study were flexibly treated with vortioxetine 5 or 10 mg/day (N = 74), and patients in the second study received vortioxetine 15 or 20 mg/day (N = 71).

• The safety and tolerability profile of vortioxetine was similar between the two studies; treatment-emergent adverse events with the highest incidence were nausea, dizziness, headache, and nasopharyngitis.

• Across both studies, improvements achieved during the preceding double-blind studies period were maintained, and additional improvements were observed with open-label treatment.

• Patients showed a mean ± SD reduction (improvement) in Montgomery and Åsberg Depression Rating Scale (MADRS) total score from open-label baseline to Week 52 of 4.3 ± 9.2 points in the 5-10 mg study, and 10.9 ± 10.0 in the 15-20 mg study.

• Post-hoc MMRM analyses of MADRS anhedonia factor scores also showed continued improvements over long-term treatment; patients showed a mean ± SE reduction from an open-label baseline to Week 52 of 3.10 ± 0.57 points in the 5-10 mg study, and 5.62 ± 0.60 in the 15-20 mg study.

Data from both studies confirm the safety and efficacy of flexibly dosed vortioxetine over 52 weeks of treatment and demonstrate that MADRS anhedonia factor scores continue to improve with long-term maintenance treatment.

Curr Med Res Opin. 2023 Mar 8:1-7. doi: 10.1080/03007995.2023.2178082.

Successful high dose antipsychotic treatment with cariprazine in patients on the schizophrenia spectrum

• Real-world evidence fills in an important gap by providing data on the effectiveness and tolerability of new medications in everyday patients.

• In this data collection form a Spanish hospital, the effectiveness and tolerability of cariprazine were evaluated in 14 patients who were admitted to the

hospital due to an acute episode of schizophrenia or schizoaffective disorder.

• Significant improvement was detected in nearly all patients (one patient dropped out) as measured by the BPRS Total, Negative symptom, Positive symptom, and Hostility scores.

• At admission, patients were markedly-moderately ill and at discharge the severity was reduced to borderline ill and normal according to the CGI-S.

• The CGI-Improvement scale also indicated very much and much improvement at discharge.

• mportantly, patients left the hospital with high doses of cariprazine, i.e., 7.5 mg/day or even 9.0 mg/day, but this did not cause safety problems; cariprazine well-tolerated as only a few patients experienced side effects such as akathisia.

The results provide novel evidence regarding the tolerability and effectiveness of cariprazine in high doses patients on the schizophrenia spectrum.

Front Psychiatry. 2023 Feb 24;14:1112697.

Depression Is Associated with an Increased Risk of Subsequent Cancer Diagnosis

• Depression and cancer share common risk factors and mechanisms of disease. The current literature has not explored the effect of depression on cancer risk.

• A Retrospective Cohort Study assessed the difference in cancer risk in patients with and without depression in a large cohort in Germany

• A total of 117,702 patients with depression were included and

matched 1:1, resulting in a cohort overall of 235,404.

• 4.9% of patients with depression compared to 4.1% without depression received at least one cancer diagnosis over 3.9 years median follow-up.

• The depression group showed an 18% increase in risk for a cancer diagnosis overall, with largest increased risk in lung cancer (HR: 1.39 [1.21-1.60], p < 0.0001), cancers of the gastro-intestinal-tract (HR: 1.30 [1.15-1.46], p < 0.0001), breast (HR: 1.23 [1.12-1.35], p < 0.0001) and urinary (HR: 1.23 [1.06-1.43], p < 0.01).

• Similarly, the incidence of cancer diagnosis overall increased by 22% for depressed patients. IRs showed no difference across cancer types.

• Study findings indicate patients with depression have an increased risk of cancer, ranging from 10% to 39% increased risk depending on the type of cancer.

• Cancer risk was highest in patients with depression for lung, GI, breast, and urinary cancer.

Brain Sci. 2023 Feb 10;13(2):302. doi: 10.3390/brainsci13020302.

The relationship between moral judgment ability, parenting style, and perfectionism in obsessive-compulsive disorder patients

• Guilt is an important part of obsessive-compulsive disorder. The abnormal moral cognition of obsessive-compulsive disorder patients may be closely related to their high level of guilt.

• The purpose of this study was to explore the development level of moral judgment in patients with obsessive-compulsive disorder and the role of parenting style and perfectionism in moral judgment development.

Front Psychol. 2023 Feb 27;14:1133880. doi: 10.3389/fpsyg.2023.1133880.

• A total of 231 patients with obsessive-compulsive disorder and 246 healthy controls were included. The results showed that,

– First, the obsessive-compulsive group scored significantly lower on moral judgment than the healthy control group.

– Second, the tendency of non-adaptive perfectionism was significantly higher in the obsessive-compulsive group than in the healthy control group.

– Third, parents’ excessive control, denial, punishment, and other parenting styles and non-adaptive perfectionism are higher than those of healthy people.

– Fourthly, the mother of obsessive-compulsive disorder patients is overly interference and protective.

Antipsychotic-related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth

• In a 3-Month Cohort-Study outh aged 4-17 years, serotonin/dopamine antagonists/partial agonists (SDA)-naïve (≤1 week exposure) or SDA- free for ≥4 weeks were followed for ≤12 weeks on clinician’s-choice aripiprazole, olanzapine, quetiapine or risperidone.

• Serum prolactin levels, SDA plasma levels and rating scale-based SeAEs were assessed monthly

• Altogether, 396 youth (age=14.0±3.1 years, male participants=55.1%, mood-spectrum disorders=56.3%, schizophrenia-spectrum disorders=24.0%, aggressive-behavior disorders=19.7%; SDA-naïve=77.8%) were followed for 10.6±3.5 weeks.

• Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole.

• Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido and erectile dysfunction were associated with prolactin levels.

• In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

J Am Acad Child Adolesc Psychiatry. 2023 Mar 13:S0890-8567(23)00125-9.

Clinical outcomes of recommended active pharmacotherapy agents from NICE guideline for post-traumatic stress disorder

• Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury.

• This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).

• Thirty articles with a total of 5170 participants were

included.

• The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD.

• In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re- experience disorder.

• Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Mar 17:110754.

Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression

• In a systematic review the changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications

• The search provided 10 psychotropics for comparison.

• Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine

at alleviating acute depressive symptoms.

• Lithium was more likely to induce dry mouth and nausea.

• Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs.

• Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia.

• Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation.

• Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD.

Int Clin Psychopharmacol. 2023 Mar 13. doi: 10.1097/YIC.0000000000000449.

Safety and effectiveness of vortioxetine for major depressive disorder

• A post-marketing surveillance study was conducted to assess the real-world safety and effectiveness of vortioxetine for the treatment of major depressive disorder (MDD) in South Korea.

• A total of 3,263 patients (mean age: 51.28 years) were included in the safety set; 1,095 were aged ≥65 years.

• The overall rate of any AEs and serious AEs were 17.13 and 1.56%, respectively.

• The majority of AEs were mild (88.32%).

• The rates of AEs did not differ statistically by age (≥65 years: 16.89% [185/1,095] versus <65 years: 17.25% [374/2,168)], p=0.7989), sex (male: 15.95% [198/1,241] versus female: 17.85% [361/2,022], p=0.1623), or liver impairment (with liver impairment: 20.90% [14/67] versus without liver impairment: 17.05% [545/3,196], p=0.4087).

• Effectiveness was assessed in 1,918 patients.

• By 24±2 weeks, there were significant clinical improvements from baseline, assessed by

– Change in Montgomery-Asberg Depression Rating Scale total score (mean±standard deviation [SD]: -10.49±9.42 points, p <0.0001),

– The proportion of patients with improved symptoms using the Clinical Global Impression – Improvement scores (79.29%),

– Digit Symbol Substitution Test (mean±SD: 4.83±9.81, p <0.0001) total scores from baseline

Vortioxetine appears to be well-tolerated and effective for treating MDD patients in the real-world setting, irrespective of age, sex, and liver impairment

Front Psychiatry. 2023 Mar 2;14:1075939.

Effects of vortioxetine on cognition and fatigue in patients with multiple sclerosis and depression

• Vortioxetine is a multimodal antidepressant drug that has been reported to have a positive impact on cognition, social function, and fatigue.

• Recently published study objective was to explore the effects of vortioxetine on these and other parameters in patients (n=25) with multiple sclerosis (MS) and depression.

• This observational case series study included patients with MS and depression who received treatment with vortioxetine for at least 6 months

• Significant improvements were observed in

– health status (EQ-5D; p = 0.002),

– mood (Beck’s Depression Inventory, BDI-II; p = 0.006),

– anxiety (State-Trait Anxiety Inventory, STAI-State; p = 0.021, and STAI-Trait; p = 0.011), and

– in the general health test (Short Form Health Survey, SF-36) for the vitality (p = 0.028) and

– mental health (p = 0.025) domains of the patients who completed the treatment.

• However, no statistically significant differences were observed in the cognitive tests related to attention, information processing speed, or fatigue

In patients with MS, vortioxetine treatment was effective in reducing

the symptoms of depression and improving anxiety, vitality, and mental health.

CNS Neurol Disord Drug Targets. 2023 Mar 21. doi: 10.2174/1871527322666230321093133.

Pharmacological Strategies for Bipolar Disorders in Acute Phases and Chronic management

• Bipolar disorders (BDs) progress into complicated forms (e.g., mixed states, rapid/irregular cycling), which are more difficult to treat and often require personalized pharmacological combinations.

• Mood stabilizers, particularly Lithium and Valproic acid (VPA), still represent the cornerstones of both acute and chronic pharmacotherapies of BDs.

• Lithium is the gold standard in BD-I and BDII with typical features.

• VPA seems more effective for atypical forms (e.g., mixed-prevalence and rapid-cycling).

• Despite appropriate mood stabilization, many patients show residual symptoms, and more than a half recur within 1-2 years, highlighting the need of additional strategies.

– The association of atypical antipsychotics (AAPs) with mood stabilizers is recurrent in the treatment of acute phases, but it is also being growingly explored in the maintenance pharmacotherapy.

– These combinations are clinically more aggressive and often needed in the acute phases, whereas simplifying pharmacotherapies to mood stabilizers only is preferable in the long-term, whenever possible.

– When mood stabilizers are not enough for maintenance treatment, Quetiapine and, less consistently, Aripiprazole have been proposed as the most advisable adjunctive strategies, for their safety and tolerability profiles.

Curr Neuropharmacol. 2023 Feb 24. doi: 10.2174/1570159X21666230224102318. Online ahead of print.

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus Nationwide study of 30,451 patients

While treatment with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3.

• 30,451 patients were identified who diagnosed with bipolar disorder in Danish Psychiatric Services.

• During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM.

• Compared with non-users of the respective drugs, no clinically or statistically significant difference in the risk of developing DM among patients receiving

– lithium (n = 11,690; HRR = 0.94, 95% CI: 0.84-1.06) or

– lamotrigine (n = 11,785; HRR = 0.89, 95% CI: 0.77-1.02).

• There was increased risk of developing DM for patients receiving

– valproate (n = 5171; HRR = 1.34, 95% CI: 1.14-1.58) and

– antipsychotics (n = 22,719; HRR = 1.65, 95% CI: 1.45-1.88).

• A clear cumulative dose-response-like association with the risk of

DM was observed for antipsychotics.

Treatment with valproate and antipsychotics-but not with lithium and lamotrigine-was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.

Bipolar Disord. 2023 Feb 8. doi: 10.1111/bdi.13308. Online ahead of print.

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression

• 2-step, open-label trial involving adults 60 years of age or older with treatment- resistant depression.

• Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline.

• Each step lasted approximately 10 weeks.

• Well-being scores improved by

– 4.83 points in aripiprazole-augmentation group

– 4.33 points in bupropion-augmentation group

– 2.04 points in switch-to-bupropion group

– 3.17 points in lithium-augmentation group; 2.18 points switch-to-nortriptyline group(difference, 0.99; 95% CI, -1.92 to 3.91)

• The difference between the aripiprazole-augmentation group and switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with prespecified threshold P value of 0.017).

• Remission occurred in

– 28.9% of patients in the aripiprazole-augmentation group

– 28.2% in the bupropion-augmentation group

– 19.3% in the switch-to-bupropion group

– 18.9% of patients in the lithium-augmentation group

– 21.5% in the switch-to-nortriptyline group

• The rate of falls was highest with bupropion augmentation compared to bupropion-augmentation, and switch-to-bupropion group; similar in the lithium-augmentation, and switch-to- nortriptyline group.

In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with

lithium augmentation or a switch to nortriptyline were similar. N Engl J Med. 2023 Mar 3. doi: 10.1056/NEJMoa2204462. Online ahead of print.

• •

Combining Ketamine and Psychotherapy for the Treatment of Posttraumatic Stress Disorder Systematic Review and Meta-Analysis

The clinical data for ketamine in PTSD are preliminary, it is hypothesized to function by rapidly facilitating long-term potentiation, thereby allowing a patient to disengage from an established pattern of thought more readily.

Ketamine has notable side effects, only lasts 1 week for PTSD, and must be administered intravenously in a hospital, rendering it impractical for long-term weekly administration.

4 studies were deemed eligible, 2 of which were of moderate quality and 2 of which were of low quality according to the GRADE assessment.

34 patients were included across all studies, with diverse traumatic experiences.

All studies demonstrated a significant reduction in symptoms.

The pooled SMD for the CAPS was −7.26 (P = .005; 95% CI, −12.28 to −2.25), while the pooled SMD for the PCL was −5.17 (P < .001; 95% CI, −7.99 to −2.35) (Figure 1).

The results of this meta-analysis indicate that ketamine-assisted psychotherapy may be highly effective, as seen by the significant improvements in symptoms on multiple measures.

This demonstrates the potential feasibility and potential of ketamine-assisted psychotherapy for PTSD.

J Clin Psychiatry. 2023;84(2):22br14564. https://doi.org/10.4088/JCP.22br14564.

Triggers for acute mood episodes in bipolar disorder: systematic review

• This is the first systematic review about triggers/precipitants of relapse in BD.

• 108 studies (case reports/case series, interventional, prospective and retrospective studies) were included.

• Antidepressant use is the trigger with the strongest evidence for manic relapse.

• There is a relative paucity of evidence concerning triggers for depressive relapses in BD.

Fasting

Antidepressant use

viral infections

brain stimulation

hormonal changes

Triggers for mania

energy drinks

Possible triggers for depression

seasonal changes

acetyl-l- carnitine

Stressful life events

Decreased sleep

St. John’s wort

Journal of Psychiatric Research. Available online 13 March 2023. In Press, Journal Pre-proof. https://doi.org/10.1016/j.jpsychires.2023.03.008

•

Real-world effectiveness of mood stabilizer use in schizophrenia

61,889 persons treated in inpatient care due to schizophrenia in Finland during 1972–2014 were evaluated

Risk of psychosis hospitalization associated with specific mood stabilizers and compared with non-use of mood stabilizers in within-individual design

Risk of non-psychiatric hospitalization (A) and hospitalization due to cardiovascular reasons (B) associated with specific mood stabilizers compared with non-use of mood stabilizers in within- individual design.

Mood stabilizer use, except use of carbamazepine, was associated with a 12% lower risk of hospitalization due to psychosis compared with non- use.

Compared to non-use, mood stabilizer use was associated with a 6% increased risk of non- psychiatric hospitalization.

Acta Psychiatr Scand.2023; 147:257–266

Days & Conferences

Day Conferences

Anxiety and Depression Awareness Week (U.S – 4-10 May)

International Congress on Mental Health (04-05 May 2023

Zurich, Switzerland)

World Schizophrenia Day (24 May) PsyCon 2023 – International Conference on Psychology & Psychiatry (06-07 May 2023

Kuala Lumpur, Malaysia)

World No Tobacco Day (31 May) Annual Meeting of the American Psychiatric Association (APA 2023 – 20-24 May 2023

San Francisco, CA, United States)

10th International Conference on Depression, Anxiety and Stress Management (22-23 May 2023

Berlin, Germany)

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