Therapeutic spectrum in psychiatry

Introduction and definitions

The concept of therapeutic spectrum is broad and can’t be fully defined at this moment in psychopharmacology as well in general pharmacology. It refers to sometimes one or both of the following concepts

. 1)  the range of beneficial clinical activities of a drug to all symptom domains of a specific diseases. Like broad spectrum anti epileptics and broad spectrum antibiotics or broad spectrum antipsychotics

. 2)  The range of total clinical activities of a drug in different systems of body. Like SSRI group of drugs act as antidepressant, anti anxiety and anti obsessive at cerebral level. Anti fungal and anti microbial at immune system level. Act as epigenetic medication at epigenetic and transcription level and possibly act as anti cancer medication at the level of neoplasia

Importance of therapeutic spectrum of a drug

1) getting ideas about full therapeutic spectrum of a drug would be good to understand about possible adverse/untoward effects Like giving 5HT2A inhibitors or SSRI (5HT2A inhibitor>SSRI) in places where blood viscosity and coagulability has to be reduced.

2) The multimorbid situations where the drug can be given can be guessed from the therapeutic spectrum of the drug
Antiepileptics are invariably drugs acting in conduction system of heart and so has some reaction with anti arrhythmia drugs. SSRI and 5HT2A antagonists are good to give in IHD, mirtazapine and NASSA group is good for gastrointestinal effects

3) The different pharmacodynamic and pharmacokinetic combination of the drug can be better done if we can find the therapeutic spectrums of the drug involved

SSRI and 5HT2A antagonists good for giving with antiplatelet drugs for comorbid hyper coagulation disorders. Lithium is a good mood stabiliser for patient receiving stem cell therapy

4) The real promise of therapeutic spectrum is the broader picture. Using every systemic effect of a drug in some form or other as therapeutic effect will reduce drug crisis as well reduce the problems of adverse drug reaction.

Drugs won’t have any adverse effect then. Only different systemic beneficial effects. But that would be expecting too much for now.

Therapeutic spectrums of common psychotropic drugs, essentially incomplete because we don’t know the full extent

Antidepressant drugs

Drugs

Mechanism of action

Cerebral effects

Epigenetic effects

Immune effects

Oncological effects

Buspirone

Partial agonist 5HT1A

GAD, TRD, SSRI induced Sexual dysfunction

Can block trans placental epigenetic transmission of stress,

Increases CD4+ T cell counts, increases IL2 mRNA, increases immune responsiveness

Poorly understood anti cancer activity, needs more research

Bupropion

NE & DA reuptake inhibitor

MDD, SAD, Nicotine Dependence
ADHD (Off label)

Inhibits DNA methylation and possibly blocks histone deacetylation

Reduces pro inflammatory cytokines (TNF alpha, gamma interferon etc)

Not explored yet

Mirtazapine

NE α2, 5HT2, 5HT3 antagonist

MDD

Changes methylation and acetylation pattern of many key genes in stress

Increases CD4+ and CD8+ T cells. Decreases TNF alpha, increases IL2

Inhibits colon cancer growth in animal studies

Escitalopram

SSRI

MDD, Panic D, GAD, S anxiety D, OCD

Decreases methylation and changes hypermethylated portions back to normal

Increased innate immunity, increased T helper 2 responses, increased activity of natural killer cells, decreases TNF alpha

Inhibits tumour growth in various solid tumours

Fluoxetine

SSRI

MDD, OCD, PTSD, BDD, PMDD, Bulimia, Trichotil, Panic D

Prominent epigenetic action, epigenetic modification of caMKII alpha gene promoter. Epigenetic modification of various growth factor promoter segment. Impacts transplacental epigenetic transmission

Reduces pro inflammatory cytokines, reduces autoimmune reactions, boosts innate immunity and humoral immunity

Suppresses tumour growth, is a chemosesitizer (p glycoprotein inhibitor)

Fluvoxamine

SSRI

MDD, OCD

Same as fluoxetine

Same as fluoxetine

Same as fluoxetine

Sertraline

SSRI

MDD,OCD

Same as fluoxetin

Same as fluoxetine with antimicrobial and antifungal action

Same as fluoxetine

Amitriptyline

SNRI & 5HT2 antagonist TCA

MDD, pain

Extreme epigenetic actions. Inhibits methylation and promotes acetylation of DNA and histone at various sites.

Inhibits acid sphingomyelinase and produces leukocyte dysfunction. Reduces autoimmunity, reduces myelopeoxidase activity

Anti tumour action by inducing mitophagy and autophagy. Silences the gloomy stem cells in glioblastoma multiforme. Also is a high producer of ROS and causes oxidative damage induced anti tumour action

Nortriptyline

NRI

MDD

Same as amitriptyline

Same as amitriptyline

Same as amitriptyline

Imipramine

SNRI

MDD, Panic D, OCD

Same as amitriptyline with additional NMDA receptor gene modification action

Same as amitriptyline

Same as amitriptyline

Clomipramine

SRI & NE metabolite reuptake inhibitor

MDD, OCD, Panic D

Same as amitriptyline with additional NMDA receptor gene modification action

Same as amitriptyline

Same as amitriptyline

Venlafaxine/ DesV

SNRI

MDD, GAD, Panic D

Widespread changes in methylation and acetylation pattern in DNA and histone

Strong immunomodulatory action, specially anti inflammatory action which is greater and different from SSRI

Not explored yet.

Duloxetine

SNRI

MDD, GAD

Same as venlafaxine

Same as venlafaxine

Not much explored, have antiglioma property

Trazodone

5HT2 antagonist, 5HT1A agonist

MDD

Anti inflammatory in brain.

Same as amitriptyline

Antipsychotic drugs

Name of drug

Possible mode of action

Cerebral uses

Epigenetic aplications

Immune aplications

Malignancy application

Phenothiazine class

D2, 5HT2, M, α1, H1

Schizophrenia & other psychoses, Bipolar Mania, Hyperactivity and severe behavioral problems

None investigated yet

Strong antifungal and antimicrobial action

Direct cytotoxic agent, chemosensitizer, good adjuvant therapy in many cancer

Haloperidol

D2

Schizophrenia & other psychoses, Bipolar Mania, Tourette’s, Hyperactivity and severe behavioral problems

Promotes DNA methylation at various sites

Anti inflammatory, suppresses helper 1 T cells and possibly promotes helper 2 T cells, suppresses innate immunity

Promotes ferroptosis and direct cytotoxicity, prevents metastasis, haloperidol metabolite II prodrug in an upcoming anticancer drug

Piperazine class

D2, 5HT2

Schizophrenia & other psychoses, Bipolar Mania, Generalized anxiety

None investigated

Antimicrobial

Direct cytotoxic, growth inhibitor

Clozapine

Moderate affinity – 5HT1A/2A/ 2C/7, D2/3,
Strong – α1, M1, H1

TRS, Suicidal young people with schizophrenia

Reduces DNA methylation and even reduces hyper methylation. Increases histone acetylation, reduces genetic silencing of regenerative genes

Stimulates innate immunity and has an extensive immunomodulatory function of which we are just scratching the surface

Not much information yet

Risperidone

Strong – D2, D3, 5HT2A/7, α1

Schiz, BD

Not much known yet

Anti inflammatory and immunomodulatory

Not much is known

Olanzapine

Moderate – D2/3, 5HT2C, α1, M1; Strong – 5HT2A, H1

Schiz, BD, TRD

Mostly like clozapine but can promote methylation along with dmethylation

Anti inflammatory at high dose, promotes oligodendrosite growth

Antitumour effects in glioblastoma cells

Quetiapine

Strong – α1, H1; Moderate – 5HT2A/7, M1; Low – D2/3

Schiz, BD-M/D

Similar to olanzapine

Not explored yet

Antimetastatic in breast cancer, cytotoxic effect and growth suppression in glioma cells, suppresses glioma stem cells

Lurasidone

Strong – D2,5HT1A/7; Moderate – 5HT2A, α1

Schiz, BD-D

Can prevent epigenetic signatures of stress from developing

Anti inflammatory and immunomodulatory

Cycline dependent kinase 2 inhibitor and that makes it valuable future anticancer drug in future

Amisulpiride

Strong – 5HT1A/2A/2C, α1, H1; Moderate – D2

Schiz, BD

Not much is known yet

Not much explored

Not explored yet

Mood stabilisers

Name

Mechanism of action

Cerebral use

Epigenetic application

Immune application

Malignancy application

Lithium

Too many but primarily intracellular second messenger system stabiliser

Bipolar disorder Antidepressant augmentation Antisuicidal agent off label

Suppresses DNA methyl transferase, increases telomerase activity

Pro inflammatory As well immunomodulatory

Inhibits metastasis, inhibits tumorogenesis, is a proposed neoadjuvant therapy for glioblastoma and pancreatic carcinoma

Valproate

Histone deacetylase inhibitor, prominent epigenetic drug,

Immunomodulatory, anti inflammatory

Radiosensitizer, direct cytotoxic, inhibitor of solid tumour, useful in myelodysplastic syndrome

Conclusion

Every drug applied to body has action on genetic and epigenetic level along cellular and supra cellular level. Also all drugs have action in all systems of body. So sum total of any drug’s action on body is a combination of these actions. All of these individual actions of a drug would be beneficial in some situations and would be detrimental in some conditions. And separating these individual action by specific drug delivery system to specific area would lead to humankind getting much more benefit form their existing drug armamentarium. There is no unimodal drug in pharmacology. It’s just our knowledge that is defective and grossly inadequate.

Reference

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