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?

Lexapro (Escitalopram) Dosing

Start escitalopram at 10 mg once daily for both depression and anxiety in adults, with the option to increase to 20 mg after at least one week if needed; adolescents with depression should also start at 10 mg daily but wait a minimum of three weeks before increasing to 20 mg. 1

Standard Adult Dosing

Major Depressive Disorder

• Initial dose: 10 mg once daily 1
• May increase to 20 mg daily after a minimum of one week if clinically indicated 1
• Both 10 mg and 20 mg doses are effective, though 20 mg did not demonstrate greater benefit than 10 mg in fixed-dose trials 1
• Administer once daily, morning or evening, with or without food 1

Generalized Anxiety Disorder

• Initial dose: 10 mg once daily 1
• May increase to 20 mg daily after a minimum of one week 1
• Pooled analysis of three trials demonstrated significant improvement beginning at week 1-2 and continuing through week 8 2
• Patients maintained on 10 mg daily showed significant improvement compared to placebo 2

Other Anxiety Disorders

• Panic disorder, social anxiety disorder, and OCD: 10-20 mg daily is effective and well-tolerated 3
• Flexible dosing of 5-10 mg daily showed efficacy in panic disorder with faster onset than citalopram 3
• Response rates and relapse prevention demonstrated across multiple anxiety disorders at 10-20 mg daily 3

Adolescent Dosing (Ages 12-17)

Major Depressive Disorder

• Initial dose: 10 mg once daily 1
• May increase to 20 mg daily after a minimum of three weeks (longer than adults) 1
• Flexible-dose trial (10-20 mg/day) demonstrated effectiveness 1

Special Populations

Elderly Patients (≥65 years)

• Recommended dose: 10 mg daily 1
• Do not routinely increase to 20 mg 1
• Lower doses reduce risk of adverse effects while maintaining efficacy 4

Hepatic Impairment

• Recommended dose: 10 mg daily 1
• Do not increase dose 1

Renal Impairment

• Mild to moderate impairment: No dosage adjustment necessary 1
• Severe impairment: Use with caution 1

Maximum Dosing and Safety Considerations

FDA-Approved Maximum

• Maximum recommended dose: 20 mg daily 5, 1
• Doses above 20 mg are not FDA-approved 5
• Higher doses carry increased risk of QT prolongation in a dose-dependent manner 5

Risks of Exceeding 20 mg Daily

• Increased likelihood of QT prolongation (similar to citalopram's boxed warning for doses >40 mg) 5
• Higher rates of common SSRI side effects including insomnia, somnolence, dizziness, and headache 5
• If 20 mg is insufficient, consider augmentation strategies (e.g., adding bupropion or mirtazapine) rather than exceeding maximum dose 5
• Alternative: switch to an SNRI such as venlafaxine (maximum 225 mg daily) or duloxetine 5

Maintenance Treatment

Duration of Treatment

• First episode of major depression: Minimum 4 months of treatment 4
• Recurrent depression: Prolonged treatment may be beneficial 4
• Systematic evaluation demonstrated benefit of maintenance treatment at 10-20 mg daily in responders 1
• Periodically reassess need for continued treatment 1

Long-Term Efficacy

• Relapse prevention studies in anxiety disorders showed continued efficacy for 24-76 weeks 3
• Risk of relapse was 4.04 times higher with placebo than escitalopram in GAD 3
• In social anxiety disorder, 22% relapsed on escitalopram versus 50% on placebo over 24 weeks 3

Discontinuation

Tapering Protocol

• Gradual dose reduction is recommended rather than abrupt cessation 1
• If intolerable symptoms occur, resume previous dose and taper more gradually 1
• Monitor for discontinuation symptoms including dizziness, headache, and mood changes 1

Clinical Efficacy Data

Onset of Action

• Symptom improvement can occur within 1-2 weeks of starting treatment 6
• Escitalopram showed earlier and clearer separation from placebo than citalopram at one-quarter to half the dosage 6
• In GAD, significant improvement observed beginning at week 1-2 2

Response and Remission Rates

• In Chinese patients with depression and anxiety, 61.7% achieved depression remission (MADRS ≤10) and 59.2% achieved functional remission (SDS ≤6) at week 8 7
• 48.1% achieved both functional and depression remission 7
• 50% of panic disorder patients experienced no panic attacks on escitalopram versus 38% on placebo 3

Tolerability Profile

Common Adverse Effects

• Nausea (5.8%), diarrhea (2.3%), dizziness (2.7%) 7
• Ejaculatory problems, insomnia, headache, and sexual dysfunction 4, 6
• Most adverse events are mild to moderate in severity 7, 6
• Nausea is typically mild and transient 6

Discontinuation Due to Adverse Effects

• Overall, 7-8% of patients withdraw due to adverse events, similar to placebo rates 3
• Number needed to harm for discontinuation: 20-90 for SSRIs as a class 4
• 25.7% of patients reported at least one treatment-emergent adverse event in an 8-week study 7

Drug Interactions

MAOI Interactions

• Allow at least 14 days between discontinuing an MAOI and starting escitalopram 1
• Allow at least 14 days after stopping escitalopram before starting an MAOI 1
• Do not start escitalopram in patients receiving linezolid or IV methylene blue due to serotonin syndrome risk 1

Serotonin Syndrome Risk

• Combining with other serotonergic medications (including some analgesics) can cause serotonin syndrome 4
• Signs include tremor, diarrhea, delirium, neuromuscular rigidity, and hyperthermia 4
• Serotonin syndrome occurs in 14-16% of SSRI overdoses 4

Screening Before Initiation

Bipolar Disorder Screening

• Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before starting escitalopram 1
• This prevents precipitation of manic episodes in undiagnosed bipolar disorder 1