What is the recommended starting dose and titration schedule of Lexapro (escitalopram) for an adult, and what are its contraindications and common side effects?

Lexapro (Escitalopram): Dosing, Contraindications, and Side Effects

Recommended Starting Dose and Titration

Start escitalopram at 10 mg once daily, which is the standard therapeutic dose for both depression and anxiety disorders in adults. 1, 2

• The 10 mg dose can be maintained as the therapeutic dose for most patients, with dose escalation to 20 mg daily considered after a minimum of one week if needed 1
• Maximum recommended daily dose is 20 mg, as higher doses are associated with QT prolongation and cardiac risks without additional therapeutic benefit 1
• The medication reaches steady-state plasma concentrations within 7-10 days of once-daily administration 3
• Peak plasma concentrations occur approximately 3-4 hours after oral administration, and absorption is not affected by food 3
• For elderly patients, adolescents, and those with hepatic impairment, no dosage adjustment is necessary as pharmacokinetics remain clinically similar to healthy young adults 3

Gradual Titration for Anxiety Disorders

• Consider starting with a subtherapeutic "test" dose (5 mg daily) to minimize initial anxiety or agitation, then titrate gradually every 2-4 weeks 1
• This slow up-titration is particularly important in younger patients who are more prone to behavioral activation/agitation early in treatment 1

Absolute Contraindications

Do not prescribe escitalopram to patients taking MAOIs or within 14 days of MAOI discontinuation, as this combination can precipitate serotonin syndrome within 24-48 hours. 1

• Avoid combining escitalopram with other serotonergic agents (tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort, triptans, other antidepressants) due to serotonin syndrome risk 1
• Do not use in patients with known hypersensitivity to escitalopram or citalopram 2

Common Side Effects

The most common adverse events that occur at rates greater than placebo include 2:

• Nausea (>10% of patients—the only side effect exceeding this threshold)
• Insomnia
• Ejaculation disorder
• Diarrhea
• Dry mouth
• Somnolence

Importantly, discontinuation rates due to adverse events with escitalopram 10 mg/day show no statistically significant difference compared to placebo. 2

• Most adverse events are mild to moderate and emerge within the first few weeks of treatment 1
• The overall discontinuation rate due to adverse events is low (7-8%), similar to placebo 1

Critical Safety Monitoring

Assess for suicidal ideation at every visit during the first 1-2 months of treatment, as the risk for suicide attempts is greatest during this initial period, particularly in patients younger than 24 years. 1

• Monitor for behavioral activation/agitation, especially during the first months and following dosage adjustments 1
• Watch for signs of serotonin syndrome: mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremor, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• Baseline ECG monitoring may be warranted in patients with cardiac risk factors, electrolyte abnormalities, or concurrent use of other QTc-prolonging medications 1

Pharmacokinetic Advantages

Escitalopram has the most favorable drug interaction profile among SSRIs, with minimal effects on CYP450 isoenzymes, making it the safest option for combination therapy. 1, 3

• Low protein binding (56%) reduces the likelihood of interactions with highly protein-bound drugs 3
• Elimination half-life of 27-33 hours supports once-daily dosing 3
• Linear and dose-proportional pharmacokinetics in the 10-30 mg/day range 3
• Discontinuation syndrome risk is lower with escitalopram compared to paroxetine or sertraline, though monitoring remains necessary 1

Treatment Duration and Response Assessment

• Allow at least 6-8 weeks at therapeutic dose (10-20 mg) before declaring treatment failure 1
• Continue treatment for 6+ months after remission for first episode of depression or anxiety 1
• For recurrent episodes (≥2), consider maintenance therapy for ≥1 year or longer 1
• Response rates of 50-70% are expected in controlled trials for anxiety disorders 1

Cognitive Side Effects

If memory impairment becomes bothersome, consider dose adjustment or switching to sertraline, which may have fewer cognitive side effects 4