What is the recommended dosing for Lexapro (escitalopram) in adults and adolescents with depression or anxiety, considering factors such as renal impairment and hepatic impairment?

Escitalopram (Lexapro) Dosing

For adults with depression or anxiety, start escitalopram at 10 mg once daily, which can be increased to a maximum of 20 mg daily after at least one week; for adolescents with depression, start at 10 mg daily and wait at least three weeks before increasing to 20 mg; for elderly patients and those with hepatic impairment, use 10 mg daily as the maximum dose. 1

Standard Adult Dosing

Major Depressive Disorder

• Initial dose: 10 mg once daily 1
• May be taken morning or evening, with or without food 1
• If dose escalation is needed, increase to 20 mg daily after a minimum of one week 1
• Fixed-dose trials showed both 10 mg and 20 mg are effective, but 20 mg did not demonstrate greater benefit over 10 mg 1
• The maximum FDA-approved dose is 20 mg daily; doses above this carry increased risk of QT prolongation in a dose-dependent manner 2

Generalized Anxiety Disorder

• Initial dose: 10 mg once daily 1
• If dose escalation is needed, increase to 20 mg daily after a minimum of one week 1
• Pooled analysis of three trials demonstrated significant superiority over placebo beginning at weeks 1-2 and continuing through week 8 3
• Patients maintained at 10 mg daily showed significant improvement compared to placebo, indicating many patients may not require dose escalation 3

Adolescent Dosing (Depression)

• Initial and recommended dose: 10 mg once daily 1
• If increasing to 20 mg, wait a minimum of three weeks (longer than the one-week wait required for adults) 1
• Flexible-dose trials (10-20 mg/day) demonstrated effectiveness in this population 1

Special Populations

Elderly Patients

• Maximum recommended dose: 10 mg daily 2, 1
• Lower doses reduce the risk of adverse effects while maintaining efficacy 2
• Do not exceed 10 mg daily in this population 1

Hepatic Impairment

• Maximum recommended dose: 10 mg daily 1
• Caution is necessary as escitalopram is metabolized by CYP isozymes, though impairment of one enzyme is unlikely to significantly affect clearance due to metabolism by three different CYP isozymes 4

Renal Impairment

• Mild to moderate renal impairment: No dosage adjustment necessary 1
• Severe renal impairment: Use with caution 1, 4
• No specific dose reduction is mandated, but careful monitoring is warranted 1

Maintenance Treatment Duration

First Episode Depression

• Treat for a minimum of 4 months beyond acute response 2
• Systematic evaluation demonstrated benefit of maintenance treatment at 10-20 mg daily in patients who responded during acute treatment 1

Recurrent Depression

• May benefit from prolonged treatment beyond the initial 4-month minimum 2
• Periodically re-evaluate the long-term usefulness for individual patients 1

Anxiety Disorders

• For GAD, efficacy beyond 8 weeks has not been systematically studied in the FDA label, though relapse-prevention studies support longer-term use 1, 5
• In relapse-prevention studies for GAD, escitalopram recipients showed 4.04 times lower risk of relapse compared to placebo over 24-76 weeks 5

Critical Safety Considerations

Pre-Treatment Screening

• Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before initiating treatment 1

Drug Interactions

• Avoid combining with other serotonergic medications due to risk of serotonin syndrome (tremor, diarrhea, delirium, neuromuscular rigidity, hyperthermia) 2
• Allow at least 14 days between discontinuing an MAOI and starting escitalopram, and vice versa 1
• Do not start escitalopram in patients receiving linezolid or intravenous methylene blue due to increased serotonin syndrome risk 1
• Use caution when co-administering with drugs metabolized by CYP2D6 (e.g., metoprolol) 4

Discontinuation

• Gradually taper rather than abruptly discontinue to minimize withdrawal symptoms 1
• If intolerable symptoms occur after dose reduction, resume the previous dose and taper more gradually 1

Common Adverse Effects

• Most frequent: ejaculatory problems, insomnia, headache, sexual dysfunction, nausea (mild and transient), and diarrhea 2, 6
• Number needed to harm for discontinuation: 20-90 for SSRIs as a class 2
• Most adverse events are mild to moderate in severity 7, 5
• Escitalopram has favorable tolerability due to being six times less potent than citalopram at histamine H1 and muscarinic receptors 4