Selective Serotonin Reuptake Inhibitors (SSRIs)

First-line for depression, GAD, panic, social anxiety, OCD, PTSD, PMDD, bulimia. Block SERT → ↑ synaptic 5-HT. Safer than older antidepressants; all equally effective — choose based on side-effect profile, interactions, and half-life.

Side Effects (Common to Class)

• GI: nausea, diarrhea (worst first 1–2 weeks — improves)
• Sexual dysfunction: ↓ libido, delayed orgasm (~30–70%) — often persistent. Bupropion augmentation can help.
• Insomnia or somnolence
• Weight gain (paroxetine > others; fluoxetine most weight-neutral)
• Hyponatremia (SIADH) — especially elderly
• Bleeding risk — ↓ platelet aggregation; caution with NSAIDs, anticoagulants
• Sweating, bruxism
• Discontinuation syndrome — "FINISH": Flu-like, Insomnia, Nausea, Imbalance, Sensory (electric shocks), Hyperarousal. Taper over 2–4 wk (except fluoxetine — can stop).

SNRIs — Serotonin-Norepinephrine Reuptake Inhibitors

Block SERT + NET. Useful when SSRIs fail, or when neuropathic pain coexists.

Atypical Antidepressants

Tricyclic Antidepressants (TCAs)

Block SERT + NET but also α1, H1, muscarinic → side-effect heavy. Lethal in overdose (cardiac arrhythmia — widened QRS from Na channel block). Rarely first-line for depression; still used for neuropathic pain, migraine prophylaxis, enuresis.

TCA Toxicity — "3 C's"

• Convulsions (seizures)
• Coma
• Cardiotoxicity (widened QRS, arrhythmia) → sodium bicarbonate is antidote

Monoamine Oxidase Inhibitors (MAOIs)

Block MAO-A (serotonin, NE) and MAO-B (dopamine). Rarely used — reserved for treatment-resistant or atypical depression. Require tyramine-free diet to avoid hypertensive crisis.

• Irreversible: phenelzine, tranylcypromine, isocarboxazid
• Selective MAO-B (low dose): selegiline (transdermal patch bypasses GI MAO) — fewer diet restrictions at 6 mg/24h patch

Hypertensive Crisis

Tyramine-rich foods (aged cheese, cured meats, fermented foods, wine, soy sauce) → unchecked NE release → severe HTN, stroke. Symptoms: severe HA, ↑ BP, sweating. Tx: phentolamine.

Washout Periods

• 2 weeks between MAOI and most serotonergic drugs
• 5 weeks from fluoxetine (long half-life) to MAOI

Mood Stabilizers

Lithium

Gold-standard for bipolar I. Only drug with demonstrated anti-suicide effect.

Monitoring

• Narrow therapeutic index: 0.6–1.2 mEq/L (acute mania up to 1.2; maintenance 0.6–0.8)
• Check trough level (12 hr post-dose) weekly until stable, then q 3–6 mo
• Baseline + periodic: TSH, BUN/Cr, pregnancy test, ECG if >40 yr

Side Effects

• Thyroid: hypothyroidism (20%)
• Renal: nephrogenic DI (polyuria, polydipsia); chronic interstitial nephritis
• Neuro: fine tremor (normal), coarse tremor (toxicity)
• Derm: acne, psoriasis
• Teratogen: Ebstein anomaly (Category D)
• Weight gain, GI upset, leukocytosis

Toxicity Triggers

• Dehydration (GI loss, heat)
• NSAIDs, ACEIs, ARBs, thiazide diuretics (↓ renal clearance)
• Low sodium diet

Valproate (Depakote)

Mania, mixed episodes, rapid cyclers. Also: seizures, migraine prophylaxis.

• Monitor: level (50–125 µg/mL), LFTs, CBC, ammonia if altered mental status
• SE: weight gain, hair loss, tremor, thrombocytopenia, pancreatitis, hyperammonemia, hepatotoxicity
• Teratogen: neural tube defects, PCOS — AVOID in women of reproductive age unless no alternative

Lamotrigine (Lamictal)

Bipolar depression / maintenance (not acute mania). Requires slow titration to avoid Stevens-Johnson syndrome / TEN.

• Rash: benign in ~10%, SJS in ~0.1% — stop if any rash appears
• Pregnancy: relatively safe; preferred mood stabilizer when feasible

Carbamazepine (Tegretol)

Mania (less preferred). Autoinduces own metabolism. SE: aplastic anemia, agranulocytosis, SIADH, SJS (HLA-B*1502 screen in Asian descent), teratogen (neural tube).

Typical (First-Generation) Antipsychotics

D2 antagonists. Effective for positive symptoms; poor effect on negative/cognitive. Higher EPS risk than atypicals.

EPS — Timeline

1. Acute dystonia (hours–days): oculogyric crisis, torticollis. Tx: IM diphenhydramine or benztropine
2. Akathisia (days–weeks): inner restlessness — NOT anxiety. Tx: β-blocker (propranolol), reduce dose, benzo
3. Parkinsonism (weeks–months): bradykinesia, tremor, rigidity. Tx: benztropine, amantadine, reduce dose
4. Tardive dyskinesia (months–years): orofacial involuntary movements; can be irreversible. Tx: switch to atypical; VMAT2 inhibitors (valbenazine, deutetrabenazine)

Atypical (Second-Generation) Antipsychotics

D2 + 5-HT2A antagonism → better negative symptom coverage, less EPS. Main downside: metabolic syndrome (weight, glucose, lipids).

Metabolic Monitoring (all atypicals)

• Baseline + q 3 mo × 1 yr, then annually: weight/BMI, waist, BP, fasting glucose, lipids, HbA1c
• Worst offenders: olanzapine > clozapine > quetiapine
• Most weight-neutral: ziprasidone, lurasidone, aripiprazole

Benzodiazepines

GABA-A positive allosteric modulators — ↑ frequency of Cl⁻ channel opening. Anxiolytic, sedative, muscle relaxant, anticonvulsant.

Risks

• Dependence & withdrawal (seizure risk — can kill like alcohol withdrawal)
• Respiratory depression with opioids / alcohol
• Falls, cognition in elderly — AVOID per Beers criteria
• Paradoxical disinhibition, especially in elderly and developmentally disabled
• Reversal: flumazenil (can precipitate seizure in chronic users)

Other Anxiolytics

• Buspirone — 5-HT1A partial agonist. Non-sedating, non-addictive, no respiratory depression. Takes 2–4 weeks to work. Good for GAD. Not effective for PRN use.
• Hydroxyzine — H1 antagonist. Sedating but non-addictive. Useful PRN or in SUD patients.
• Propranolol — β-blocker. Performance anxiety (pre-situational, 10–40 mg); PTSD hyperarousal.
• Gabapentin / Pregabalin — α2δ calcium channel modulation. Off-label anxiety, PTSD, alcohol use. Pregabalin has abuse potential.

Stimulants & ADHD Medications

Safety

• Baseline: growth, BP, HR, cardiac history, family history of sudden death
• Monitor: growth, BP, HR at every visit; watch for tics, appetite suppression, insomnia
• Abuse potential: Schedule II — assess diversion risk in adolescents / college students

Medications for Addiction Treatment (MAT)

Alcohol Use Disorder

• Naltrexone (PO daily or monthly IM Vivitrol) — ↓ craving, ↓ reward. Avoid with opioid use (precipitates withdrawal).
• Acamprosate — stabilizes glutamate. Renal dosing. Good choice with liver disease.
• Disulfiram — aversive (blocks aldehyde DH → flushing, N/V, ↓ BP with alcohol). Requires motivated patient.
• Gabapentin, topiramate — off-label, emerging evidence

Opioid Use Disorder

• Buprenorphine (partial µ agonist) ± naloxone (Suboxone) — office-based; ceiling effect ↓ overdose
• Methadone (full µ agonist) — via federally regulated OTP only
• Naltrexone (µ antagonist, monthly IM) — requires 7–10 days opioid-free first
• Naloxone (µ antagonist) — overdose reversal. Distribute to all at-risk patients.

Tobacco Use Disorder

• Varenicline (Chantix) — partial α4β2 nicotinic agonist. Most effective.
• Bupropion SR — ↓ craving
• Nicotine replacement — patch + PRN gum/lozenge combo

Sleep Medications

First-line for chronic insomnia = CBT-I (not meds). Sleep hygiene, stimulus control, sleep restriction.

Pediatric Prescribing Considerations

• Only a few psych meds are FDA-approved in pediatrics; most use is off-label but evidence-based
• Fluoxetine: MDD ≥8, OCD ≥7
• Escitalopram: MDD ≥12, GAD ≥7
• Sertraline: OCD ≥6
• Fluvoxamine: OCD ≥8
• Risperidone / aripiprazole: autism-associated irritability
• Stimulants: ADHD typically ≥6 yr (methylphenidate ≥4 in some formulations)
• All pediatric SSRI use: black-box suicidality, weekly monitoring × 4 wks, biweekly × 4, then monthly
• "Start low, go slow" — pediatric doses are typically half adult starting doses

Pregnancy & Lactation Quick Table