Psychotherapeutic agents

Psychotherapeutic agents, also referred to as psychotropics, are a broad class of pharmacological compounds designed to alter mood, perception, cognition, or behavior by acting on the central nervous system (CNS). These agents are foundational in the treatment of mental health disorders such as depression, anxiety, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), insomnia, and neurodevelopmental conditions.

The therapeutic effect of these agents primarily involves modulation of neurotransmitter systems, including serotonin, dopamine, norepinephrine, GABA, and glutamate. Depending on the target receptor or transporter, psychotherapeutic agents may function as agonists, antagonists, reuptake inhibitors, enzyme inhibitors, or modulators of ion channels.

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1. Classification of Psychotherapeutic Agents

Psychotherapeutic agents are grouped based on their primary mechanism of action and therapeutic indication. The major classes include:

1. Antidepressants

2. Antipsychotics

3. Mood stabilizers

4. Anxiolytics

5. Hypnotics and sedatives

6. Psychostimulants

7. Cognitive enhancers

8. Psychotherapeutic combination drugs

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2. Antidepressants

Antidepressants are indicated for major depressive disorder (MDD), anxiety disorders, PTSD, OCD, eating disorders, and neuropathic pain.

Major subclasses:

• Selective serotonin reuptake inhibitors (SSRIs): fluoxetine, sertraline, escitalopram

• Serotonin-norepinephrine reuptake inhibitors (SNRIs): venlafaxine, duloxetine

• Tricyclic antidepressants (TCAs): amitriptyline, nortriptyline

• Monoamine oxidase inhibitors (MAOIs): phenelzine, tranylcypromine

• Atypical antidepressants:

  • Bupropion (NDRI)

  • Mirtazapine (NaSSA)

  • Trazodone, vilazodone, vortioxetine

Mechanism:

They increase synaptic levels of serotonin, norepinephrine, and/or dopamine by inhibiting their reuptake or metabolism.

Adverse effects:

• Sexual dysfunction (SSRIs/SNRIs)

• Weight gain (mirtazapine)

• Sedation (TCAs, mirtazapine)

• Anticholinergic effects (TCAs)

• Hypertensive crisis (MAOIs + tyramine)

• Serotonin syndrome (when combined with serotonergic drugs)

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3. Antipsychotics (Neuroleptics)

Used in schizophrenia, bipolar disorder, psychotic depression, delirium, and agitation.

Classes:

• Typical antipsychotics (first-generation): haloperidol, chlorpromazine

• Atypical antipsychotics (second-generation): risperidone, olanzapine, quetiapine, aripiprazole, clozapine

Mechanism:

• Typical: Block dopamine D2 receptors

• Atypical: Block D2 and serotonin 5-HT2A receptors (and others)

Adverse effects:

• Extrapyramidal symptoms (EPS): dystonia, akathisia, parkinsonism (more with typicals)

• Tardive dyskinesia (chronic use)

• Metabolic syndrome: weight gain, diabetes, dyslipidemia (atypicals)

• Agranulocytosis (clozapine)

• QT prolongation (ziprasidone, haloperidol)

• Neuroleptic malignant syndrome

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4. Mood Stabilizers

Prescribed in bipolar I/II disorder, cyclothymia, and schizoaffective disorder.

Agents:

• Lithium carbonate: gold standard for mania and maintenance

• Anticonvulsants:

  • Valproic acid

  • Carbamazepine

  • Lamotrigine

  • Oxcarbazepine

Mechanism:

Modulate voltage-gated ion channels, enhance GABA transmission, and/or reduce glutamate signaling.

Adverse effects:

• Lithium: nephrotoxicity, hypothyroidism, tremor, teratogenicity (Ebstein anomaly)

• Valproate: hepatotoxicity, pancreatitis, neural tube defects

• Carbamazepine: hyponatremia, agranulocytosis, Stevens-Johnson syndrome

• Lamotrigine: rash, SJS risk (slow titration is critical)

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5. Anxiolytics

Primarily used in generalized anxiety disorder (GAD), panic disorder, social anxiety, and adjustment disorders.

Agents:

• Benzodiazepines: diazepam, lorazepam, alprazolam

• Buspirone: partial 5-HT1A agonist

• Hydroxyzine: antihistamine with sedative properties

• Pregabalin: GABA analogue

Mechanism:

• BZDs enhance GABA-A receptor activity → CNS inhibition

• Buspirone modulates serotonin activity without sedation

Adverse effects:

• Sedation

• Dependence and withdrawal (BZDs)

• Cognitive impairment

• Paradoxical disinhibition

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6. Hypnotics and Sedatives

Indicated for insomnia, preoperative sedation, and sleep disorders.

Agents:

• Benzodiazepines: temazepam, triazolam

• Non-BZDs (Z-drugs): zolpidem, zaleplon, eszopiclone

• Melatonin receptor agonists: ramelteon

• Orexin receptor antagonists: suvorexant, lemborexant

Mechanism:

• Enhance GABAergic activity (BZDs, Z-drugs)

• Target circadian (melatonin) or wakefulness (orexin) systems

Adverse effects:

• Tolerance, dependence

• Morning sedation

• Sleepwalking, parasomnias

• Cognitive effects in elderly (BZDs)

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7. Psychostimulants and Cognitive Enhancers

Used for ADHD, narcolepsy, and sometimes off-label for cognitive dysfunction in dementia.

Agents:

• Methylphenidate, dextroamphetamine, lisdexamfetamine

• Modafinil, armodafinil

• Atomoxetine: selective norepinephrine reuptake inhibitor (non-stimulant)

• Donepezil, rivastigmine, galantamine: acetylcholinesterase inhibitors

• Memantine: NMDA receptor antagonist

Mechanism:

• Increase dopamine and norepinephrine in CNS

• Enhance acetylcholine signaling in Alzheimer’s

Adverse effects:

• Appetite suppression

• Insomnia

• Elevated blood pressure

• Tics

• Risk of misuse or diversion (controlled substances)

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8. Psychotherapeutic Combination Agents

Fixed-dose combinations that include:

• Antidepressant + antipsychotic (e.g., olanzapine + fluoxetine)

• Antidepressant + anxiolytic (e.g., chlordiazepoxide + amitriptyline)

• Dextromethorphan + bupropion (Auvelity): NMDA antagonist + NDRI for MDD

These combinations are designed to target multiple neurotransmitter pathways and are often used in treatment-resistant cases.

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9. Adverse Effects Across Classes

Class	Common Adverse Effects
Antidepressants	GI upset, sexual dysfunction, suicidality (young adults), serotonin syndrome
Antipsychotics	EPS, metabolic syndrome, sedation, hyperprolactinemia
Mood stabilizers	Organ toxicity (liver, thyroid, kidney), weight gain, rash
Anxiolytics	Dependence, sedation, rebound anxiety
Hypnotics	Sleepwalking, dependence, daytime drowsiness
Stimulants	Insomnia, anorexia, tics, cardiovascular risks

10. Drug–Drug Interactions

Psychotherapeutic agents often interact via:

• Cytochrome P450 inhibition/induction (especially 2D6, 3A4, 1A2)

• Additive CNS depression (e.g., benzodiazepines + alcohol)

• Serotonin syndrome with multiple serotonergic agents

• QT prolongation (many antipsychotics, TCAs, SSRIs)

• Pharmacodynamic antagonism (e.g., stimulants vs sedatives)

Patients taking multiple CNS drugs must be monitored closely.

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11. Special Considerations

Patient Group	Key Considerations
Elderly	Risk of falls, cognitive impairment, Beers criteria apply
Pregnancy	Category C/D for many drugs; consider risks/benefits
Children	Suicidal ideation risk with antidepressants
Renal/Hepatic impairment	Adjust dose based on metabolism/excretion

12. Therapeutic Monitoring

• Lithium: Monitor serum levels (0.6–1.2 mEq/L), renal/thyroid function

• Valproate: LFTs, CBC, drug levels

• Clozapine: Weekly WBC/ANC monitoring due to agranulocytosis risk

• SSRIs/SNRIs: Monitor for efficacy after 4–6 weeks, suicidality in youth

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13. Emerging Agents and Research Areas

• Rapid-acting antidepressants (e.g., ketamine, esketamine nasal spray)

• Psychedelic-assisted therapy (e.g., psilocybin, MDMA in PTSD)

• Cannabinoids in anxiety, schizophrenia (ongoing studies)

• Orexin antagonists for insomnia and depression

• Digital therapeutics and pharmacogenomics in psychiatric prescribing

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14. Regulatory Classification and Legal Status

Many psychotherapeutic agents are controlled substances under national drug schedules:

Agent	Controlled Schedule
Benzodiazepines	Schedule IV (U.S.)
Stimulants	Schedule II (U.S.)
Modafinil	Schedule IV
Antipsychotics, SSRIs	Prescription-only (non-controlled)
Psychedelics	Schedule I (for now; pending FDA trials)

15. Key Examples by Class

Class	Generic Name	Brand Name
SSRI	Sertraline	Zoloft
SNRI	Duloxetine	Cymbalta
TCA	Amitriptyline	Elavil
Atypical Antipsychotic	Aripiprazole	Abilify
Mood Stabilizer	Lithium	Lithobid
Benzodiazepine	Lorazepam	Ativan
Non-BZD Hypnotic	Zolpidem	Ambien
Stimulant	Lisdexamfetamine	Vyvanse
Cognitive Enhancer	Donepezil	Aricept