Escitalopram

Indications

• FDA-approved for major depressive disorder in adults and in pediatric patients 12 years and older at 10-20 mg once daily.
• FDA-approved for generalized anxiety disorder in adults and in pediatric patients 7 years and older, using the same dose range.
• Off-label but strongly supported for panic disorder, social anxiety disorder, and obsessive-compulsive disorder in adults.
• Off-label for premenstrual dysphoric disorder and for vasomotor symptoms of menopause when hormone therapy is unsuitable.
• Consistently ranked among the most efficacious and best-tolerated antidepressants in the Cipriani network meta-analysis of 21 agents.
• Frequently used off-label in medically complex and post-stroke patients because of its low interaction burden and predictable kinetics.

Mechanism of action

• Pure S-enantiomer of citalopram and the most selective serotonin transporter inhibitor available, with negligible activity at other transporters.
• Binds both the primary orthosteric transporter site and an allosteric site, which slows dissociation and may explain its potency advantage.
• Removing the inactive R-enantiomer eliminates a competitive brake, so 10 mg escitalopram is roughly equivalent to 20 to 40 mg citalopram.
• Sustained transporter blockade desensitizes 5-HT1A autoreceptors over weeks, which is the step that tracks clinical antidepressant response.
• Minimal muscarinic, histaminic, and adrenergic affinity accounts for its low rates of sedation, dry mouth, and orthostatic hypotension.

Pharmacokinetics

• Bioavailability is about 80 percent and unaffected by food; peak concentrations occur roughly five hours after an oral dose.
• Half-life is 27 to 32 hours, supporting once-daily dosing at any time of day, with steady state reached in about one week.
• Metabolized by CYP2C19 and CYP3A4 with a minor CYP2D6 role; the demethyl metabolite contributes little to clinical activity.
• CYP2C19 poor metabolizers show roughly twofold higher exposure, and guidelines suggest a 50 percent starting dose reduction in that group.
• Only a weak CYP2D6 inhibitor, making it one of the safest antidepressants to add to complex medical regimens.

Dosing

• Start 10 mg PO once daily, morning or evening; increase to the maximum of 20 mg/day after at least one week if response is partial.
• Fixed-dose depression trials did not show added benefit at 20 mg over 10 mg, so escalate for clear partial response rather than reflexively.
• Pediatric depression starts at 10 mg/day with escalation to 20 mg no sooner than three weeks; pediatric generalized anxiety follows the adult schedule.
• The recommended dose is 10 mg/day in older adults and in hepatic impairment; no adjustment is needed in mild to moderate renal impairment.
• Available as 5, 10, and 20 mg tablets and a 1 mg/mL oral solution, which allows the very small decrements useful in slow tapers.
• Taper gradually over two to four weeks when stopping to avoid dizziness, paresthesia, irritability, and sleep disturbance.

Adverse effects

• Nausea, insomnia, somnolence, fatigue, and increased sweating are the common early complaints, usually resolving within two weeks.
• Sexual dysfunction affects roughly 30-40 percent of treated patients and is the most frequent reason for long-term discontinuation.
• QTc prolongation is dose-dependent but smaller than with citalopram, and escitalopram carries no comparable label dose ceiling.
• Hyponatremia from SIADH occurs mainly in older adults on diuretics and can present as confusion, unsteadiness, or new-onset seizure.
• Serotonin syndrome, increased bleeding with NSAIDs or anticoagulants, and treatment-emergent mania are the serious prescribing concerns.
• Weight change is modest, averaging roughly 1 kg over a year, less than paroxetine and comparable to sertraline in cohort studies.

Monitoring

• Assess suicidality, activation, and agitation weekly for the first four weeks and after each dose change, most intensively under age 25.
• Check serum sodium at baseline and within two to four weeks in older adults, diuretic users, or anyone with new confusion or falls.
• Obtain an ECG only when combining with other QT-prolonging drugs or in patients with known cardiac conduction disease.
• Track response with PHQ-9 or GAD-7 at baseline and every two to four weeks, and reassess diagnosis if there is no change by week six.
• Screen for bipolar disorder before starting and recheck sleep need and goal-directed activity if improvement seems abrupt or excessive.

Interactions

• Contraindicated with MAOIs and within 14 days of stopping one, and with linezolid or intravenous methylene blue.
• Contraindicated with pimozide because escitalopram raises pimozide exposure and both agents prolong the QT interval.
• CYP2C19 inhibitors such as omeprazole, fluvoxamine, and fluconazole raise escitalopram levels; consider capping at 10 mg/day in that setting.
• Additive serotonin syndrome risk with triptans, tramadol, fentanyl, lithium, linezolid, and St. John's wort.
• Increases bleeding risk with aspirin, NSAIDs, and anticoagulants through depletion of platelet serotonin stores.

Special populations

• No consistent teratogenic signal in pregnancy; third-trimester use carries small risks of neonatal adaptation syndrome and pulmonary hypertension.
• Compatible with breastfeeding at a relative infant dose of about 5 percent, with sertraline still generally preferred for a new start.
• Approved from age 12 for depression and age 7 for generalized anxiety, the broadest pediatric anxiety labeling among the SSRIs.
• In patients over 65 the recommended dose is 10 mg/day given reduced clearance and increased hyponatremia and falls risk.
• Hepatic impairment also limits dosing to 10 mg/day; renal impairment needs no change unless creatinine clearance is under 20 mL/min.

Clinical pearls

• 10 mg escitalopram is roughly equivalent to 20 to 40 mg citalopram, without the hard QT ceiling.
• Fixed-dose trials show little added benefit at 20 mg, so push the dose only for real partial response.
• Best pediatric anxiety labeling of the SSRIs, approved for generalized anxiety from age 7.