What are the potential adverse effects of escitalopram (Lexapro)?

Adverse Effects of Escitalopram

Escitalopram is generally well tolerated with a predictable side effect profile consisting primarily of mild to moderate, transient adverse events, though serious effects including suicidal ideation, serotonin syndrome, and sexual dysfunction require careful monitoring.

Common Adverse Effects (≥5% incidence)

The most frequently reported adverse effects in adults with major depressive disorder include:

• Nausea (15%) - the most common gastrointestinal effect, typically mild and transient 1
• Insomnia (9%) - may require dose timing adjustment 1
• Ejaculation disorder (9% in males) - primarily ejaculatory delay 1
• Diarrhea (8%) 1
• Fatigue (5%) 1
• Somnolence (6%) 1
• Increased sweating (5%) 1
• Dizziness (5%) 1

In generalized anxiety disorder, the profile is similar with nausea, ejaculation disorder, insomnia, fatigue, decreased libido, and anorgasmia being most prominent (≥5% and approximately twice placebo rates) 1.

Serious Adverse Effects Requiring Monitoring

Suicidal Ideation and Behavior

• All SSRIs carry a boxed warning for increased suicidal thinking and behavior in patients through age 24 years 2
• The pooled absolute risk is 1% with antidepressants versus 0.2% with placebo, yielding a number needed to harm of 143 2
• Close monitoring is essential, especially during the first months of treatment and following dose adjustments 2

Serotonin Syndrome

• Potentially life-threatening condition caused by elevated brain serotonin levels, particularly when combining serotonergic medications 2
• Symptoms include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness that can be fatal 2
• Absolute contraindication: combining escitalopram with MAOIs (phenelzine, isocarboxazid, moclobemide, linezolid) 2
• Exercise caution when combining with other serotonergic drugs including SNRIs, TCAs, tramadol, dextromethorphan, triptans, and St. John's Wort 2, 1

Behavioral Activation/Agitation

• More common in younger children than adolescents and in anxiety disorders compared to depressive disorders 2
• Manifests as motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, or aggression 2
• May occur early in treatment, with dose increases, or with concomitant drugs that inhibit SSRI metabolism 2
• Supports slow up-titration and close monitoring, particularly in younger patients 2

Sexual Dysfunction

• Includes decreased libido (3%), ejaculation disorder (9% in males), impotence (3% in males), and anorgasmia (2% in females) 1
• These effects are persistent and may impact treatment adherence 2

Other Serious Effects

• Abnormal bleeding - especially with concomitant NSAIDs or aspirin; rare events include ecchymosis, epistaxis, petechiae, and hemorrhage 2
• Seizures - rare but documented 2
• Hypomania/mania - rare reports, difficult to distinguish from behavioral activation 2

Discontinuation-Related Adverse Events

Treatment Discontinuation Rates

• 6% of adults with MDD discontinued due to adverse events (versus 2% with placebo) 1
• Nausea (2%) and ejaculation disorder (2% of males) were the most common reasons for discontinuation in adults with MDD 1
• In GAD, 8% discontinued (versus 4% with placebo), with nausea (2%), insomnia (1%), and fatigue (1%) being primary reasons 1

Discontinuation Syndrome

• Escitalopram/citalopram have lower risk of discontinuation syndrome compared to shorter-acting SSRIs like paroxetine 2
• Symptoms include dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances, and anxiety 2
• The 27-33 hour elimination half-life supports once-daily dosing and reduces withdrawal risk 3

Pediatric-Specific Considerations

In children and adolescents (ages 6-17), the adverse effect profile is generally similar to adults, with additional effects including:

• Back pain 1
• Urinary tract infection 1
• Vomiting 1
• Nasal congestion 1
• Possible slowed growth rate and weight changes requiring monitoring 1
• Insomnia was the most common reason for discontinuation (1% versus 0% placebo) 1

Drug Interaction Considerations

Escitalopram has a favorable drug interaction profile with negligible effects on cytochrome P450 isoenzymes 2, 3:

• Citalopram/escitalopram have the least effect on CYP450 isoenzymes compared to other SSRIs, resulting in lower propensity for drug interactions 2
• Coadministration with cimetidine increased escitalopram exposure by 72%, and omeprazole by 51%, though these changes were not considered clinically relevant 3
• Low protein binding (56%) reduces likelihood of interactions with highly protein-bound drugs 3

Clinical Pitfalls and Monitoring Recommendations

• Avoid rapid dose escalation - slow up-titration at 1-2 week intervals for shorter half-life SSRIs minimizes behavioral activation and optimizes benefit-to-harm ratio 2
• Screen for bipolar disorder before initiating treatment to avoid precipitating mania 1
• Monitor for QT prolongation - while less concerning than with citalopram (which has dose-related QT effects >40mg/day), caution is warranted with concomitant QT-prolonging drugs 2
• Educate patients and families about warning signs of suicidality, serotonin syndrome, and behavioral activation before treatment initiation 2
• Most adverse effects emerge within the first few weeks and are generally mild to moderate and transient 2