What are the side effects of Lexapro (escitalopram)?

Side Effects of Lexapro (Escitalopram)

The most common side effects of Lexapro include nausea (15%), insomnia (9%), ejaculation disorder (9% in males), diarrhea (8%), somnolence (6%), dizziness (5%), increased sweating (5%), and fatigue (5%), with most adverse effects being mild to moderate and transient, typically emerging within the first few weeks of treatment. 1

Most Common Side Effects (≥5% and Twice Placebo Rate)

In adults with major depressive disorder:

• Nausea (15% vs 7% placebo) 1
• Insomnia (9% vs 4% placebo) 1
• Ejaculation disorder - primarily ejaculatory delay (9% vs <1% placebo in males) 1
• Diarrhea (8% vs 5% placebo) 1
• Somnolence (6% vs 2% placebo) 1
• Dizziness (5% vs 3% placebo) 1
• Increased sweating (5% vs 2% placebo) 1
• Fatigue (5% vs 2% placebo) 1

In generalized anxiety disorder patients, the profile is similar with additional emphasis on:

• Decreased libido (≥5%) 1
• Anorgasmia (≥5%) 1

Serious Adverse Effects Requiring Close Monitoring

Suicidal Ideation and Behavior

All patients through age 24 years require close monitoring for suicidal thinking and behavior, particularly during the first months of treatment and following dose adjustments, with a pooled absolute risk of 1% versus 0.2% with placebo (number needed to harm = 143). 2, 3 This warrants a boxed warning from the FDA. 2

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition characterized by mental status changes, autonomic hyperactivity (fever, tachycardia, tachypnea), and neuromuscular abnormalities (tremor, hyperreflexia, hypertonia), particularly when combining escitalopram with other serotonergic medications. 2, 3 Avoid combining with MAOIs and exercise caution with other serotonergic drugs including triptans, tramadol, St. John's Wort, and other antidepressants. 1

Behavioral Activation/Agitation

Motor or mental restlessness, insomnia, impulsiveness, disinhibited behavior, and aggression may occur early in treatment (first month), with dose increases, or with concomitant drugs that inhibit SSRI metabolism. 2, 3 This is more common in younger children than adolescents and in anxiety disorders compared to depressive disorders. 2

Mania/Hypomania

Rare reports of mania or hypomania can occur, typically appearing later in treatment than behavioral activation and may persist after discontinuation, requiring active psychiatric management. 2

Pediatric-Specific Side Effects

In children and adolescents (ages 6-17), the adverse effect profile is generally similar to adults, but additional reactions occurring at ≥2% include:

• Back pain 1
• Urinary tract infection 1
• Vomiting 1
• Nasal congestion 1
• Increased thirst 1
• Abnormal increase in muscle movement or agitation 1
• Nosebleed 1
• Difficult urination 1
• Heavy menstrual periods 1
• Possible slowed growth rate and weight changes requiring monitoring during treatment 1

Neonatal Effects from Third-Trimester Exposure

Infants exposed to escitalopram in the third trimester may develop a constellation of signs including continuous crying, irritability, jitteriness, tremors, hypertonia, tachypnea, feeding difficulty, sleep disturbance, hypoglycemia, and seizures, with onset ranging from hours to days after birth and typically resolving within 1-2 weeks. 2

Discontinuation-Related Effects

Escitalopram has a lower risk of discontinuation syndrome compared to shorter-acting SSRIs like paroxetine, with symptoms including dizziness, fatigue, myalgias, headaches, nausea, insomnia, sensory disturbances, and anxiety. 3, 4 Taper over 10-14 days when discontinuing to minimize withdrawal symptoms. 4

Treatment Discontinuation Rates

In major depressive disorder trials:

• 6% of adults discontinued due to adverse events (vs 2% placebo) 1
• 10% discontinued at 20 mg/day dose (vs 4% at 10 mg/day and 3% placebo) 1
• 3.5% of pediatric patients discontinued (vs 1% placebo) 1
• Nausea (2%) and ejaculation disorder (2% in males) were the most common reasons for discontinuation 1

In generalized anxiety disorder trials:

• 8% discontinued due to adverse events (vs 4% placebo) 1
• Nausea (2%), insomnia (1%), and fatigue (1%) led to discontinuation 1

Additional Adverse Effects (2-5% Incidence)

• Sexual dysfunction: Impotence (3% in males), anorgasmia (2% in females), decreased libido (3%) 1
• Gastrointestinal: Constipation (3%), indigestion (3%), abdominal pain (2%), dry mouth 1
• Respiratory: Rhinitis (5%), sinusitis (3%) 1
• Psychiatric: Decreased appetite (3%) 1
• General: Influenza-like symptoms (5%) 1

Critical Clinical Pitfalls and Monitoring Recommendations

Avoid rapid dose escalation; use slow up-titration at 1-2 week intervals to minimize behavioral activation and optimize the benefit-to-harm ratio. 3 The best-fitting model for SSRI response shows clinically significant improvement by week 6 and maximal improvement by week 12 or later, supporting gradual titration. 2

Monitor for QT prolongation when combining with other QT-prolonging drugs, though this is less concerning with escitalopram than with citalopram. 3

Educate patients and families before treatment initiation about warning signs of suicidality, serotonin syndrome, and behavioral activation. 3

Most adverse effects emerge within the first few weeks of treatment and are generally mild and temporary. 5, 6 Only nausea occurs in >10% of escitalopram-treated patients. 7