citalopram

**Mechanism:** Selectively inhibits presynaptic serotonin (5-HT) reuptake transporter (SERT), increasing synaptic serotonin. Therapeutic effect is delayed 4-6 weeks (downregulation/desensitization of receptors, increased BDNF/neuroplasticity). Citalopram is a racemic mixture; escitalopram is the active S-enantiomer (more potent, with a somewhat lower QT risk at equivalent efficacy).

**Indications:** Major depressive disorder (FDA-approved); also used off-label or alongside other SSRIs for GAD, panic disorder, OCD, PTSD, social anxiety disorder, PMDD, and bulimia nervosa (fluoxetine is the FDA-approved agent for bulimia).

**Pharmacokinetics:** Hepatic metabolism mainly by CYP2C19 (also CYP3A4, minor 2D6). Half-life ~35 hours. Relatively few CYP interactions compared with fluoxetine, paroxetine, and fluvoxamine, so it is often chosen in polypharmacy and elderly patients. CYP2C19 inhibitors (omeprazole, cimetidine, fluvoxamine) or poor metabolizers raise levels.

**Adverse effects (high-yield):** - **Dose-dependent QT prolongation / torsades de pointes.** FDA max 40 mg/day; max 20 mg/day in age >60, hepatic impairment, CYP2C19 poor metabolizers, or those taking CYP2C19 inhibitors. Avoid in congenital long QT, uncorrected hypokalemia/hypomagnesemia, and with other QT-prolonging drugs (e.g., antiarrhythmics class IA/III, macrolides, fluoroquinolones, antipsychotics, ondansetron). - **Serotonin syndrome**, especially combined with MAOIs, linezolid, tramadol, meperidine, triptans, St. John's wort, or MDMA: triad of mental status changes, autonomic instability (hyperthermia, tachycardia, diaphoresis), and neuromuscular hyperactivity (clonus, hyperreflexia, tremor). Treat with discontinuation, supportive care, benzodiazepines, and cyproheptadine (5-HT2A antagonist) if needed. - **Hyponatremia/SIADH**, mostly in elderly patients. - **Sexual dysfunction** (decreased libido, anorgasmia, delayed ejaculation), which is the most common reason for noncompliance. Options include switching to bupropion or adding it. - GI upset, nausea, diarrhea, insomnia or somnolence, headache, and weight changes. - Increased bleeding risk (platelet serotonin depletion), especially with NSAIDs, aspirin, or anticoagulants. - **Black box warning:** increased suicidal thinking/behavior in children, adolescents, and young adults (<25 years) early in treatment. - Activation of mania or hypomania in unrecognized bipolar disorder (screen before starting). - **SSRI discontinuation syndrome:** flu-like symptoms, dizziness, "brain zaps," irritability, and insomnia. Less common with long half-life agents (fluoxetine) and more common with paroxetine. Taper to avoid it. - Pregnancy: paroxetine is the main concern (cardiac malformations). Third-trimester SSRI exposure is associated with neonatal adaptation syndrome and a small risk of persistent pulmonary hypertension of the newborn (PPHN). Sertraline is generally preferred in pregnancy/lactation.

**Contraindications:** Concurrent MAOI use (or within 14 days of stopping one; 5 weeks after fluoxetine), concurrent pimozide, and congenital long QT syndrome. Wait 14 days after stopping citalopram before starting an MAOI.

**Board pearls:** An elderly patient on citalopram who develops syncope or palpitations suggests torsades from QT prolongation. An elderly patient with confusion or seizure suggests SIADH hyponatremia. Exam question distractors often include confusing SSRI features with TCA toxicity (anticholinergic effects, QRS widening, treated with sodium bicarbonate) or with MAOI hypertensive crisis (tyramine).