Side Effects of Lexapro (Escitalopram)
Lexapro (escitalopram) commonly causes gastrointestinal symptoms (nausea 15%, diarrhea 8%), sexual dysfunction (ejaculatory delay 9% in males, anorgasmia 2% in females), sleep disturbances (insomnia 9%, somnolence 6%), and neuropsychiatric effects (dizziness 5%, fatigue 5%), with most adverse effects being mild to moderate and transient. 1
Common Side Effects (≥5% incidence)
The most frequently reported adverse effects in adults include:
Gastrointestinal Effects
- Nausea (15%) - the most common side effect, typically mild and transient 1
- Diarrhea (8%) 1
- Dry mouth (5%) 1
- Constipation (3%), indigestion (3%), abdominal pain (2%) 1
Sexual Dysfunction
- Ejaculation disorder (9% in males) - primarily ejaculatory delay 1
- Decreased libido (3%) 1
- Anorgasmia (2% in females) 1
- Impotence (3% in males) 1
Sexual dysfunction occurs to a similar or lower extent compared to paroxetine, but to a greater extent than bupropion 2
Neuropsychiatric Effects
Other Common Effects
- Increased sweating (5%) 1
- Influenza-like symptoms (5%) 1
- Rhinitis (5%), sinusitis (3%) 1
- Decreased appetite (3%) 1
- Shaking/tremors 1
Serious Adverse Effects
Cardiovascular Concerns
- QT interval prolongation - dose-dependent risk, particularly at 20 mg/day doses 3, 4
- Citalopram/escitalopram should not exceed 40 mg/day in adults or 20 mg/day in adults over 60 years due to risk of Torsade de Pointes, ventricular tachycardia, and sudden death 3
- ECG monitoring is recommended in patients with cardiac risk factors or on higher doses 4
Serotonin Syndrome
- Develops within 24-48 hours when combining serotonergic medications 3, 5
- Characterized by mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, tachypnea, diaphoresis, shivering) 3
- Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness 3
- Contraindicated with MAOIs and requires caution when combining with other serotonergic drugs including SSRIs, SNRIs, tramadol, dextromethorphan, St. John's Wort, and amphetamines 3
- Case reports document serotonin syndrome with escitalopram monotherapy at 30 mg/day 6
Bleeding Risk
- Abnormal bleeding can occur, especially with concomitant aspirin or NSAIDs 3
- Rare bleeding events include ecchymosis, hematoma, epistaxis, petechiae, and hemorrhage 3
- Gastrointestinal bleeding risk increases (OR 1.2-1.5) with SSRIs and SNRIs 3
Suicidality
- Age-related risk: slightly increased in adults 18-24 years (OR 2.30), neutral in adults 25-64 years, protective in adults ≥65 years (OR 0.06) 3
- Risk highest within 1-2 months of initiation or dose increase 3
- Low risk overall with escitalopram, with no completed suicides reported in clinical trials 4
Hyponatremia
- Occurs in 0.5-12% of older adults 3
- OR 3.3 for SSRIs compared to other drug classes 3
- Typically develops within the first month of treatment 3
Discontinuation Syndrome
Escitalopram should be tapered over 10-14 days to minimize withdrawal symptoms 3, 4:
- Symptoms include dizziness, fatigue, lethargy, general malaise, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, sensory disturbances, paresthesias, anxiety, irritability, and agitation 3
- Escitalopram has a half-life of 27-33 hours, which may reduce discontinuation symptoms compared to shorter-acting SSRIs like paroxetine 4, 7
- Lightheadedness and dizziness may be more pronounced during discontinuation 4
- Discontinuation symptoms are milder with escitalopram than with paroxetine 8
Special Populations
Pediatric Patients (6-17 years)
Additional adverse effects beyond those in adults include 1:
- Back pain
- Urinary tract infection
- Vomiting
- Nasal congestion
- Increased thirst
- Abnormal increase in muscle movement or agitation
- Nosebleed
- Difficult urination
- Heavy menstrual periods
- Possible slowed growth rate and weight changes requiring monitoring 1
Pregnancy and Neonatal Effects
Third-trimester SSRI exposure causes neonatal adaptation syndrome 3:
- Symptoms include continuous crying, irritability, jitteriness, restlessness, shivering, fever, tremors, hypertonia, tachypnea, respiratory distress, feeding difficulty, sleep disturbance, hypoglycemia, and seizures 3
- Onset ranges from hours to days after birth 3
- Usually resolves within 1-2 weeks, though symptoms may persist up to 4 weeks 3
- Persistent pulmonary hypertension of the newborn (PPHN) risk with number needed to harm of 286-351 3
- SSRI treatment should be continued during pregnancy at the lowest effective dose, as withdrawal may harm the mother-infant dyad 3
Breastfeeding
- Escitalopram transfers into breast milk in low concentrations 3
- Infant plasma levels are typically undetectable 3
- Potential adverse effects in infants are documented only in case reports and include irritability and decreased feeding 3
Drug Interactions
Escitalopram has the least effect on CYP450 isoenzymes compared to other SSRIs, resulting in lower propensity for drug interactions 3:
- May interact with drugs that prolong QT interval 3
- Cimetidine increases escitalopram exposure by 72%, omeprazole by 51% (not considered clinically relevant) 7
- Strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) may decrease efficacy 3
- Ritonavir (potent CYP3A4 inhibitor) does not affect escitalopram pharmacokinetics 7
Management Strategies
Minimizing Side Effects
- Start with lower doses (10 mg/day) and gradually titrate to minimize gastrointestinal and CNS side effects 4
- Take medication at bedtime if daytime dizziness is problematic 4
- Ensure adequate hydration and rise slowly from sitting/lying positions to minimize orthostatic effects 4
- Most adverse effects are mild, transient, and resolve within the first few weeks of treatment 8, 2
Initial Adverse Effects
- Anxiety or agitation can occur initially, making it advisable to start with a subtherapeutic "test" dose 3
- Gastrointestinal effects typically occur within the first 2 weeks, are mild in 70-80% of cases, and resolve within the first month in 60-65% 3