Psychiatric medications are among the most widely prescribed drug classes. They target neurotransmitter systems involved in mood, anxiety, cognition, and psychosis. Understanding their mechanisms, efficacy, side effects, and drug interactions is essential for safe and effective use.
Antidepressants
SSRIs (Selective Serotonin Reuptake Inhibitors)
SSRIs are first-line for depression, anxiety disorders, OCD, and PTSD. They block the serotonin transporter (SERT), increasing synaptic serotonin levels. Common SSRIs include escitalopram (10-20 mg), citalopram (20-40 mg — max 20 mg over 60 due to QT prolongation), sertraline (50-200 mg), fluoxetine (20-80 mg), paroxetine (20-50 mg), and fluvoxamine (100-300 mg). Onset of therapeutic effect: 2-4 weeks for initial response, 6-8 weeks for full effect. Common side effects: GI upset (nausea, diarrhea — often transient), sexual dysfunction (30-60% — delayed ejaculation, anorgasmia, decreased libido — persistent, a leading cause of non-adherence), insomnia or sedation (depending on agent — fluoxetine activating, paroxetine sedating), headache, and initial anxiety. Discontinuation syndrome (dizziness, paresthesias, flu-like symptoms, nausea, irritability) occurs with abrupt cessation, especially with shorter half-life agents (paroxetine, venlafaxine). SSRIs may increase suicidal ideation in children and young adults (black box warning — risk is highest in first weeks of treatment). Paroxetine is associated with birth defects if taken in first trimester (especially cardiac malformations). Citalopram carries a dose-dependent QT prolongation risk.
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
SNRIs inhibit both SERT and NET. Venlafaxine (75-375 mg) acts as an SSRI at low doses and SNRI at higher doses. Desvenlafaxine (25-100 mg) is the active metabolite of venlafaxine with a simpler dosing profile (no need to titrate to SNRI effect). Duloxetine (30-120 mg) is also effective for neuropathic pain, fibromyalgia, and chronic musculoskeletal pain. SNRIs have similar efficacy to SSRIs for depression and anxiety. Side effects include GI upset, sexual dysfunction (lower incidence than SSRIs), insomnia, and sweating. Venlafaxine can increase blood pressure at higher doses (requires BP monitoring). Discontinuation syndrome is common.
Atypical Antidepressants
Bupropion (Wellbutrin, 150-450 mg) inhibits dopamine and norepinephrine reuptake. It is unique: no sexual dysfunction, weight loss or neutral, activating (good for fatigue, low energy). It increases seizure risk at high doses or in patients with seizure disorders or eating disorders (bulimia, anorexia). It is contraindicated in patients with seizure disorders, eating disorders, and patients abruptly discontinuing alcohol or benzodiazepines. Bupropion is also effective for smoking cessation (Zyban).
Mirtazapine (Remeron, 15-45 mg) enhances noradrenergic and serotonergic transmission through alpha-2 antagonism. It is sedating (at lower doses — 7.5-15 mg — due to histamine H1 blockade), increases appetite and weight gain, and has a lower incidence of sexual dysfunction and GI side effects than SSRIs. Good for depression with insomnia and weight loss.
Vortioxetine (Trintellix, 10-20 mg) has multimodal activity (SERT inhibition plus 5-HT receptor modulation). It has fewer sexual side effects and less weight gain than SSRIs. Efficacy is comparable to SSRIs.
Tricyclic Antidepressants
TCAs (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine) block SERT and NET but also block histamine (sedation, weight gain), acetylcholine (anticholinergic: dry mouth, constipation, urinary retention, blurred vision, cognitive impairment), and alpha-1 receptors (orthostatic hypotension). They are effective but have a narrow therapeutic index and are cardiotoxic in overdose (QT prolongation, arrhythmias, seizures). TCAs are rarely first-line but are useful for treatment-resistant depression, neuropathic pain (amitriptyline, nortriptyline), and insomnia (low-dose doxepin, amitriptyline). Nortriptyline has fewer anticholinergic and sedative effects than amitriptyline and is preferred in older adults. Clomipramine is the most serotonergic TCA, effective for OCD.
MAOIs (Monoamine Oxidase Inhibitors)
MAOIs (phenelzine, tranylcypromine, selegiline) inhibit MAO-A and/or MAO-B, preventing breakdown of serotonin, norepinephrine, and dopamine. They are the most effective antidepressants but are rarely used due to dietary restrictions (tyramine-containing foods — aged cheese, cured meats, fermented foods, wine, beer — can cause hypertensive crisis) and drug interactions (SSRIs, SNRIs, TCAs — serotonin syndrome risk). The selegiline transdermal patch (Emsam) at the lowest dose (6 mg/24h) does not require dietary restrictions. MAOIs are reserved for treatment-resistant depression and atypical depression.
Antipsychotics
First-Generation (Typical) Antipsychotics
FGAs block dopamine D2 receptors. Low potency (chlorpromazine 100-400 mg, thioridazine) are more sedating and anticholinergic. High potency (haloperidol 2-20 mg, fluphenazine, thiothixene) have more extrapyramidal side effects. Indications: schizophrenia, acute mania, agitation, Tourette syndrome (haloperidol), and nausea (prochlorperazine). Side effects: acute dystonia (muscle spasms, especially in young men — treat with benztropine or diphenhydramine), parkinsonism (rigidity, tremor, bradykinesia), akathisia (restlessness, inability to sit still), tardive dyskinesia (involuntary orofacial movements, potentially irreversible — risk 5% per year), hyperprolactinemia (galactorrhea, gynecomastia, sexual dysfunction, amenorrhea), QT prolongation (especially thioridazine, haloperidol IV), and neuroleptic malignant syndrome (rigidity, fever, altered mental status, autonomic instability — medical emergency).
Second-Generation (Atypical) Antipsychotics
SGAs block D2 and 5-HT2A receptors. The 5-HT2A blockade reduces EPS risk and improves negative symptoms. Common SGAs: risperidone (2-8 mg), olanzapine (5-20 mg), quetiapine (150-800 mg), aripiprazole (10-30 mg), ziprasidone (80-160 mg), paliperidone (3-12 mg), lurasidone (40-120 mg), clozapine (100-900 mg), and brexpiprazole (1-4 mg). All are available in oral formulations; risperidone, olanzapine, aripiprazole, paliperidone, and haloperidol have long-acting injectable formulations.
Metabolic side effects are the major concern with SGAs: weight gain (most with olanzapine, clozapine; least with lurasidone, ziprasidone), diabetes and insulin resistance, and dyslipidemia (increased triglycerides and cholesterol). Olanzapine and clozapine carry the highest metabolic risk. Monitoring: weight, BMI, waist circumference, fasting glucose or A1c, and fasting lipids at baseline and regularly (at 12 weeks, then annually). Clozapine is uniquely effective for treatment-resistant schizophrenia (30% respond where other antipsychotics fail) and reduces suicidality. It requires mandatory weekly blood monitoring due to 1-2% risk of agranulocytosis. Clozapine causes significant weight gain, hypersalivation, sedation, constipation, and myocarditis.
Mood Stabilizers
Lithium is the gold standard for bipolar disorder — it reduces manic episodes, depressive episodes, and suicide risk (a uniquely robust effect on suicide). Dose: 900-1,800 mg/day, targeting serum levels of 0.6-1.2 mEq/L (manic phase) and 0.6-0.8 mEq/L (maintenance). Side effects: polyuria and polydipsia (nephrogenic diabetes insipidus — can lead to chronic renal disease with long-term use), hypothyroidism (10-20%), tremor, weight gain, and acne. Lithium has a narrow therapeutic index — toxicity (ataxia, confusion, seizures, coma, death) occurs at levels above 1.5 mEq/L. Monitoring: renal function, TSH, and serum lithium every 3-6 months. Drug interactions: NSAIDs, ACE inhibitors, ARBs, and diuretics increase lithium levels.
Valproate (divalproex, valproic acid) is effective for acute mania and mixed episodes, with a faster onset than lithium. Dose: 750-2,000 mg/day targeting serum levels of 50-125 mcg/mL. Side effects: weight gain, tremor, sedation, hair loss, PCOS-like effects (in women — menstrual irregularities, hyperandrogenism), and hepatotoxicity (especially in children under 2). It is teratogenic (neural tube defects — contraindicated in pregnancy). Monitoring: LFTs, CBC, and valproate levels.
Lamotrigine is effective for bipolar depression and maintenance (it is the best-studied agent for preventing depressive episodes). It has minimal effect on acute mania. Dose: titrate slowly to 200 mg/day (25 mg x 2 weeks, 50 mg x 2 weeks, 100 mg x 1 week, then 200 mg). The risk of Stevens-Johnson syndrome (0.08% in adults) is reduced with slow titration. Carbamazepine is used for acute mania, especially in rapid cycling and in patients with secondary mania (neurologic injury). It induces CYP3A4 (significant drug interactions). Monitoring: CBC, LFTs, electrolytes, and carbamazepine levels.
Anxiolytics
Benzodiazepines enhance GABA-A receptor activity, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects. They are effective for acute anxiety but carry risks of tolerance, dependence, withdrawal, sedation, cognitive impairment, and falls (especially in older adults). Long-term use is generally discouraged. Short-acting: alprazolam (Xanax), lorazepam (Ativan). Medium-acting: clonazepam (Klonopin), diazepam (Valium). Buspirone is a non-benzodiazepine anxiolytic (partial 5-HT1A agonist) — no abuse potential, no sedation, but takes 2-4 weeks for effect. Used for generalized anxiety disorder.
Summary
SSRIs are first-line for depression and anxiety (sexual dysfunction is the most troublesome side effect). SNRIs add norepinephrine effects (BP monitoring needed). Bupropion has no sexual dysfunction but lowers seizure threshold. Antipsychotics carry EPS (FGAs) and metabolic (SGAs) risks. Clozapine is uniquely effective for treatment-resistant schizophrenia but requires blood monitoring. Lithium is the gold standard mood stabilizer with suicide-protective effects but requires careful monitoring. Benzodiazepines are effective short-term anxiolytics with dependence risk.