Introduction
Psychiatric medications are central to the treatment of mental disorders, which affect one in five adults globally. Psychopharmacology encompasses drugs that modulate neurotransmitter systems including serotonin, norepinephrine, dopamine, GABA, and glutamate. Treatment selection is based on diagnosis, symptom profile, tolerability, patient preference, and individual genetic variation.
Antidepressants
Major Classes
| Class | Mechanism | Examples | Efficacy | Onset | Sexual Dysfunction | Weight Gain | Other Key Effects |
|---|---|---|---|---|---|---|---|
| SSRIs | SERT inhibition (presynaptic) | Fluoxetine, sertraline, citalopram, escitalopram, paroxetine, fluvoxamine | First-line for MDD, GAD, panic, OCD, PTSD, bulimia, PMDD | 2-6 weeks | High (30-60%), especially paroxetine | Modest (paroxetine highest) | GI upset, insomnia (sertraline, fluoxetine), sedation (paroxetine) |
| SNRIs | SERT + NET inhibition | Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran | First-line for MDD, GAD, DPN, fibromyalgia (duloxetine), chronic MSK pain | 2-6 weeks | Moderate | Low-moderate | Nausea, sweating, BP increase (venlafaxine >200 mg), withdrawal syndrome |
| NDRI | NET + DAT inhibition | Bupropion | MDD, smoking cessation, seasonal affective disorder | 2-4 weeks | Very low (<5%) | Low (may cause weight loss) | Seizure risk (dose-dependent >450 mg/day), anxiety, insomnia (activating) |
| NaSSA | Alpha-2 antagonism + 5-HT2/3 antagonism | Mirtazapine | MDD (especially with insomnia, weight loss) | 1-2 weeks | Low | High (increased appetite, sedation) | Sedation (useful for insomnia), dry mouth, constipation |
| SARI | 5-HT2A antagonism + SERT inhibition | Trazodone, nefazodone | MDD, insomnia (trazodone low dose) | 2-6 weeks | Low (trazodone), moderate (nefazodone) | Low | Sedation (very high for trazodone), priapism (rare), orthostatic hypotension |
| TCAs | NET + SERT inhibition (nonspecific) | Amitriptyline, nortriptyline, imipramine, clomipramine | MDD (second/third-line), neuropathic pain, OCD (clomipramine), anxiety | 2-4 weeks | High | High | Anticholinergic (dry mouth, constipation, blurred vision, urinary retention), cardiac toxicity in overdose, sedation |
| MAOIs | MAO-A and/or MAO-B inhibition | Phenelzine, tranylcypromine, selegiline (transdermal) | Atypical depression, treatment-resistant depression, panic | 2-4 weeks | Variable | Variable | Hypertensive crisis with tyramine (diet restrictions), drug interactions; selegiline transdermal bypasses GI MAO at low dose |
Antidepressant Dosing
| Drug | Starting Dose | Therapeutic Dose | Maximum Dose | Half-Life | Notes |
|---|---|---|---|---|---|
| Fluoxetine | 20 mg daily | 20-40 mg daily | 80 mg | 4-6 days (plus active metabolite) | Long half-life; lowest withdrawal risk; activating; CYP2D6 inhibition |
| Sertraline | 25-50 mg daily | 50-200 mg daily | 200 mg | 26 hours | Good tolerability; pregnancy safety data; diarrhea common |
| Citalopram | 20 mg daily | 20-40 mg daily | 40 mg (max 20 mg if >60 years) | 35 hours | QT prolongation >40 mg; generally well-tolerated |
| Escitalopram | 10 mg daily | 10-20 mg daily | 20 mg | 27-32 hours | S-enantiomer of citalopram; well-tolerated; few drug interactions |
| Paroxetine | 20 mg daily or 10 mg slowly | 20-40 mg daily | 60 mg | 21-24 hours | Most weight gain; most sexual dysfunction; most withdrawal; not recommended in pregnancy |
| Venlafaxine XR | 37.5-75 mg daily | 150-225 mg daily | 375 mg | 4-5 hours (desvenlafaxine: 11 hours) | BP monitoring required; severe withdrawal syndrome; active metabolite |
| Duloxetine | 30-60 mg daily | 60 mg daily | 120 mg | 12 hours | Also for DPN, fibromyalgia, chronic MSK pain; CYP1A2 inhibition |
| Bupropion XL | 150 mg daily | 150-300 mg daily | 450 mg (300 XL) | 21 hours (XL) | Seizure risk in predisposed; no sexual dysfunction; activating |
| Mirtazapine | 15 mg qHS | 30-45 mg daily | 45 mg | 20-40 hours | Sedation at lower doses (15 mg > 30 mg due to histamine vs. NE effect) |
| Trazodone | 50-150 mg qHS (for sleep) | 150-400 mg daily (depression) | 600 mg | 5-9 hours | Priapism (rare, 1/1000-1/10,000); orthostatic hypotension |
| Amitriptyline | 25-50 mg qHS | 75-200 mg daily (divided or qHS) | 300 mg | 10-28 hours | Potentially lethal in overdose; anticholinergic burden |
Switching and Discontinuation
| Strategy | Description | Example |
|---|---|---|
| Cross-taper | Gradually taper first drug while introducing second | Decrease paroxetine 10 mg/wk while increasing escitalopram 5 mg/wk |
| Direct switch | Stop drug A, start drug B immediately | Only when safety concern (MAOI washout) |
| Taper and wait | Taper drug A, wait, then start drug B | MAOI to SSRI: 2-week washout (5 weeks for fluoxetine) |
| Discontinuation syndrome | Prevent by slow taper (10-25% reduction every 2-4 weeks) | Fluoxetine (long half-life): less withdrawal; paroxetine, venlafaxine: worst withdrawal |
Antipsychotics
First-Generation (Typical)
| Drug | Potency | Equivalent Dose (mg) | EPS Risk | Anticholinergic | Sedation | Orthostatic Hypotension | Prolactin Elevation |
|---|---|---|---|---|---|---|---|
| Haloperidol | High | 2 | Very high | Very low | Low | Low | High |
| Fluphenazine | High | 2 | Very high | Very low | Low | Low | High |
| Perphenazine | Medium | 8 | Moderate | Low | Moderate | Moderate | Moderate |
| Chlorpromazine | Low | 100 | Low | High | High | High | Moderate |
| Thioridazine | Low | 100 | Low | Very high | High | High | Moderate |
| Loxapine | Medium | 10 | High | Low | Moderate | Moderate | High |
Second-Generation (Atypical)
| Drug | D2/5-HT2A | Dose Range | EPS Risk | Metabolic | Weight Gain | Prolactin | Sedation | Anticholinergic | QT Prolongation |
|---|---|---|---|---|---|---|---|---|---|
| Risperidone | 5-HT2A » D2 | 1-8 mg daily | Moderate (dose-dependent >6 mg) | Moderate | Moderate | High | Moderate | Low | Low |
| Olanzapine | 5-HT2A > D2 | 5-20 mg daily | Low | Very high | Very high | Low | High | Moderate | Low |
| Quetiapine | 5-HT2A > D2 | 150-800 mg daily (IR); 400-800 mg (XR) | Very low | Moderate | Moderate | Low | High | Moderate | Low |
| Aripiprazole | D2 partial agonist | 10-30 mg daily | Low (akathisia) | Low | Low | Low | Low | Very low | Low |
| Ziprasidone | 5-HT2A > D2 | 80-160 mg daily | Low | Low | Very low | Low | Moderate | Very low | Moderate |
| Paliperidone | 5-HT2A » D2 | 3-12 mg daily | Moderate | Moderate | Moderate | High | Moderate | Low | Low |
| Lurasidone | 5-HT2A > D2 | 40-160 mg daily | Low | Low | Very low | Low | Low-moderate | Very low | Low |
| Clozapine | 5-HT2A > D2 (weak D2) | 12.5-900 mg daily | Very low | Very high | Very high | Very low | Very high | Very high | Moderate (1-2% myocarditis) |
Clozapine Monitoring
| Parameter | Frequency | Action |
|---|---|---|
| Absolute neutrophil count (ANC) | Weekly x18 weeks, then q2wk x1 year, then q4wk | Discontinue if ANC <1000 (benign ethnic neutropenia: <500) |
| Myocarditis screening | Baseline, q2wk x2 months | Symptoms: chest pain, SOB, fever; echo, troponin |
| Metabolic panel | Baseline, q3 months | Monitor weight, glucose, lipids |
| Therapeutic level | 350-600 ng/mL | Dose adjustment for efficacy/toxicity |
Mood Stabilizers
Lithium
| Parameter | Details |
|---|---|
| Mechanism | Inositol depletion, GSK-3 inhibition, neuroprotection (not fully understood) |
| Indications | Bipolar I (mania, maintenance), bipolar II, augmentation in depression |
| Initial dose | 300 mg BID-TID (titrate based on serum levels) |
| Therapeutic level | Acute mania: 0.8-1.2 mEq/L; Maintenance: 0.6-1.0 mEq/L |
| Toxic level | >1.5 mEq/L (mild toxicity); >2.0 mEq/L (moderate-severe); >3.0 mEq/L (life-threatening) |
| Half-life | 18-24 hours (longer with age, renal impairment) |
| Monitoring | Serum level q3-6 months; TSH, creatinine, calcium q6-12 months |
| Adverse effects | Polyuria/polydipsia (nephrogenic DI), hypothyroidism, tremor, weight gain, cognitive dulling, acne, psoriasis, teratogenicity (Ebstein anomaly) |
| Drug interactions | NSAIDs, thiazides, ACEi/ARB increase lithium levels; theophylline, caffeine decrease |
Valproate (Valproic Acid, Divalproex)
| Parameter | Details |
|---|---|
| Mechanism | GABA increase, HDAC inhibition, voltage-gated Na channel blockade |
| Indications | Bipolar mania (acute), epilepsy, migraine prophylaxis, off-label: agitation, aggression |
| Initial dose | 250-500 mg BID (titrate every 3-7 days) |
| Therapeutic level | Bipolar: 50-125 mcg/mL; Epilepsy: 50-100 mcg/mL |
| Monitoring | Level q3-6 months; LFTs, CBC q6-12 months |
| Adverse effects | Weight gain (common), tremor, hair loss, thrombocytopenia, PCOS, hepatotoxicity (rare, higher in children), pancreatitis, teratogenicity (neural tube defects) |
| Drug interactions | Inhibits CYP2C9; displaces protein-bound drugs |
Lamotrigine
| Parameter | Details |
|---|---|
| Mechanism | Voltage-gated Na channel stabilization, glutamate release inhibition |
| Indications | Bipolar maintenance (depression-prophylaxis), epilepsy, off-label: bipolar depression (acute) |
| Initial dose | 25 mg daily x2 weeks, then 50 mg daily x2 weeks (double if on enzyme-inducer; half if on valproate) |
| Therapeutic dose | Bipolar: 100-200 mg daily; Epilepsy: 200-400 mg daily |
| Monitoring | Clinical monitoring for rash |
| Adverse effects | Rash (10% benign, 0.1-0.8% Stevens-Johnson syndrome/TEN), headache, dizziness, insomnia, tremor |
| Key risk | SJS/TEN - slow titration critical; discontinue if any rash unless clearly non-drug-related |
Carbamazepine
| Parameter | Details |
|---|---|
| Mechanism | Voltage-gated Na channel blockade, glutamate inhibition |
| Indications | Bipolar mania, epilepsy, trigeminal neuralgia, off-label: bipolar maintenance |
| Initial dose | 200 mg BID (titrate slowly) |
| Therapeutic level | Bipolar: 4-12 mcg/mL; Epilepsy: 4-12 mcg/mL |
| Monitoring | Level, CBC, CMP, LFTs, BMP q3-6 months |
| Adverse effects | Dizziness, sedation, ataxia, hyponatremia (SIADH), neutropenia/agranulocytosis, SJS/TEN (HLA-B*1502 screening in Asian patients), CYP induction (autoinduction, drug interactions) |
| Drug interactions | Strong CYP3A4 inducer (reduces levels of OCPs, antipsychotics, antidepressants, warfarin, many others) |
Anxiolytics and Sedative-Hypnotics
Benzodiazepines
| Drug | Onset | Half-Life | Duration | Equipotent Dose (mg) | Metabolism | Active Metabolite | Indications |
|---|---|---|---|---|---|---|---|
| Diazepam (Valium) | Fast (IV: immediate; PO: 15-30 min) | 20-80 hours | Long | 5 | CYP3A4, CYP2C19 | Yes (desmethyldiazepam, 80-200h) | Anxiety, seizures, alcohol withdrawal, muscle spasm |
| Lorazepam (Ativan) | Intermediate (PO: 30-60 min; IV: 5-10 min) | 10-20 hours | Intermediate | 1 | Glucuronidation | No | Anxiety, sedation, status epilepticus (IV) |
| Alprazolam (Xanax) | Fast (PO: 15-30 min) | 6-12 hours | Short-intermediate | 0.5 | CYP3A4 | No | Panic disorder, anxiety (high abuse potential) |
| Clonazepam (Klonopin) | Intermediate (PO: 30-60 min) | 18-50 hours | Long | 0.25-0.5 | CYP3A4, nitroreduction | No | Panic, seizures, REM behavior disorder |
| Chlordiazepoxide (Librium) | Slow (PO: 1-2 hours) | 5-30 hours | Long | 10-25 | CYP450 | Yes | Alcohol withdrawal |
| Temazepam (Restoril) | Slow (PO: 1-2 hours) | 8-12 hours | Short | 15-30 | Glucuronidation | No | Insomnia |
| Oxazepam (Serax) | Slow (PO: 1-3 hours) | 5-15 hours | Short | 15-30 | Glucuronidation | No | Alcohol withdrawal (well-tolerated in elderly) |
| Midazolam (Versed) | Very fast (IV: 1-3 min; PO: 15 min) | 2-5 hours | Very short | NA | CYP3A4 | Minimal | Procedural sedation, status epilepticus |
Non-Benzodiazepine Anxiolytics and Sedatives
| Drug | Mechanism | Dose | Indications | Key Notes |
|---|---|---|---|---|
| Buspirone | 5-HT1A partial agonist | 10-30 mg BID-TID | GAD (chronic) | No sedation, no abuse potential, no withdrawal; delayed onset 2-4 weeks; not for panic |
| Zolpidem (Ambien) | GABA-A alpha-1 agonist | 5-10 mg qHS (IR); 6.25-12.5 mg (CR) | Insomnia | No abuse potential; no significant respiratory depression; delayed onset 1-2 hours |
| Ramelteon | MT1/MT2 agonist | 8 mg qHS | Sleep onset insomnia | No abuse potential; no significant respiratory depression; delayed onset 1-2 hours |
| Doxepin (Silenor) | H1 antagonist | 3-6 mg qHS | Sleep maintenance insomnia | No abuse potential; anticholinergic at higher doses |
| Suvorexant | Orexin antagonist | 10-20 mg qHS | Insomnia (sleep onset + maintenance) | No abuse potential; next-day sedation |
| Hydroxyzine | H1 antagonist | 25-100 mg q6h PRN | Anxiety, insomnia, pruritus | Anticholinergic, sedation, no abuse potential |
| Propranolol | Non-selective beta-blocker | 10-40 mg PRN | Performance anxiety, situational anxiety | No abuse potential; contraindicated in asthma, bradycardia |
| Gabapentin | Alpha-2-delta Ca channel | 100-1200 mg TID | Off-label: anxiety, alcohol withdrawal | Requires dose adjustment in renal impairment |
Stimulants and ADHD Medications
| Drug | Mechanism | Duration | Dose Range | Key Adverse Effects | Controlled Substance |
|---|---|---|---|---|---|
| Methylphenidate IR | DAT + NET inhibition | 3-5 hours | 5-20 mg BID-TID | Insomnia, appetite suppression, headache, anxiety, tic exacerbation | CII |
| Methylphenidate ER (Ritalin LA, Concerta, Metadate CD) | Same | 8-12 hours | 18-72 mg daily (Concerta); 20-60 mg daily (Ritalin LA) | Same; Concerta has unique delivery system | CII |
| Dexmethylphenidate (Focalin, Focalin XR) | DAT + NET inhibition (d-threo isomer) | 4-6 hours (IR); 10-12 hours (XR) | 5-20 mg day (IR); 10-40 mg daily (XR) | Similar to methylphenidate; may be better tolerated | CII |
| Amphetamine salts (Adderall, Adderall XR) | DAT + NET inhibition + VMAT2 | 4-6 hours (IR); 12 hours (XR) | 5-40 mg daily (IR divided); 10-40 mg daily (XR) | Similar; weight loss; growth suppression with chronic use | CII |
| Lisdexamfetamine (Vyvanse) | Prodrug of dextroamphetamine | 10-14 hours | 10-70 mg daily | Same as amphetamine; less abuse potential (prodrug) | CII |
| Atomoxetine | NET inhibitor | 12-24 hours | 40-100 mg daily | Low abuse potential; delayed onset (4-6 weeks); hepatotoxicity (rare) | Not controlled |
| Clonidine ER (Kapvay) | Alpha-2 agonist | 12-24 hours | 0.1-0.4 mg daily | Sedation, hypotension, dry mouth, rebound hypertension | Not controlled |
| Guanfacine ER (Intuniv) | Alpha-2A agonist | 12-24 hours | 1-7 mg daily | Less sedation than clonidine; same other effects | Not controlled |
Conclusion
Psychopharmacology requires systematic diagnosis, evidence-based medication selection, careful dosing, monitoring for adverse effects, and suicide risk assessment. Individualized treatment accounts for symptom profile, comorbidities, concurrent medications, and patient preferences. Key principles include starting low and going slow, allowing adequate time for response, managing adverse effects proactively, and considering psychotherapy in combination with medication for best outcomes.