What are the potential side effects of sertraline (Selective Serotonin Reuptake Inhibitor) in patients, particularly those with a history of mental health conditions or suicidal ideation?

Sertraline Side Effects

Sertraline commonly causes gastrointestinal symptoms (particularly diarrhea and nausea), sexual dysfunction, headache, insomnia, dizziness, and increased sweating, with nausea being the most frequent reason for discontinuation. 1, 2

Most Common Side Effects

Gastrointestinal Effects

• Nausea and vomiting occur in 21-30% of patients and represent the leading cause of treatment discontinuation 2, 3
• Sertraline causes diarrhea at higher rates than other SSRIs (including bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, and venlafaxine) 1
• Dry mouth, heartburn, and constipation are frequently reported 2, 4

Neurological and Psychiatric Effects

• Headache affects up to 17 per 1,000 person-months of therapy 2
• Insomnia occurs in 16-28% of patients and represents a common discontinuation reason 2, 3
• Somnolence and fatigue affect 10-13% and 10-12% of patients respectively 2
• Dizziness is commonly reported across all patient populations 1, 2

Sexual Dysfunction

• Sexual side effects are strongly dose-related and represent a leading cause of treatment discontinuation and non-compliance 2
• Manifestations include delayed ejaculation or ejaculation failure, decreased libido, anorgasmia, and erectile dysfunction 2, 4
• Absolute rates are likely underreported in clinical trials 1
• Sertraline has lower rates of sexual dysfunction compared to paroxetine 1

Other Common Effects

• Increased sweating affects 7-15% of patients 2, 4
• Weight changes may occur, though sertraline causes less weight gain than mirtazapine or paroxetine 1, 4

Serious Adverse Effects Requiring Monitoring

Suicidality (Black Box Warning)

• All patients, particularly those aged 24 years or younger, must be monitored closely for suicidal thinking and behavior, especially during the initial months of treatment and after dose changes 1, 4
• The absolute risk is 1% with antidepressants versus 0.2% with placebo (risk difference 0.7%, number needed to harm = 143) 4
• Starting at higher doses rather than normal starting doses increases the risk of deliberate self-harm and suicide 1

Behavioral Activation

• Motor or mental restlessness, insomnia, impulsiveness, disinhibited behavior, and aggression may occur, particularly in younger children and those with anxiety disorders 4
• More common early in treatment or with dose increases 4
• Slow up-titration minimizes this risk 2, 4

Serotonin Syndrome

• Life-threatening condition caused by elevated brain serotonin levels 4
• Absolutely contraindicated with MAO inhibitors 1, 3
• Risk increases dramatically when combining with other serotonergic medications (SNRIs, tricyclics, opioids, stimulants, dextromethorphan, triptans, illicit drugs) 2, 4
• Requires immediate hospitalization and discontinuation of all serotonergic agents 4

Other Serious Effects

• Mania or hypomania can occur, typically appearing later in treatment and may persist after discontinuation 4
• Rare but serious: seizures, abnormal bleeding, reversible cerebral vasoconstriction syndrome 3
• Hepatotoxicity: asymptomatic transaminase elevations occur in approximately 0.8% of patients, usually within 1-9 weeks, and resolve with discontinuation 3
• Severe skin reactions (Stevens-Johnson syndrome, vasculitis, photosensitivity) are rare but potentially fatal 3

Discontinuation Syndrome

• Sertraline must be tapered gradually rather than abruptly discontinued 1, 2, 4
• Sertraline is particularly associated with discontinuation syndrome 2
• Symptoms include dizziness, nausea, headache, fatigue, irritability, anxiety, insomnia, and sensory disturbances 2

Critical Monitoring Parameters

Initial Phase (First Few Months)

• Close monitoring for clinical worsening, suicidality, and unusual behavioral changes is mandatory, especially during the first months and after dose adjustments 1
• Most side effects emerge within the first few weeks 4
• Contact (in-person or telephone) should occur after treatment initiation to review adherence and current status 1

Ongoing Monitoring

• Maximal therapeutic improvement typically occurs by week 12 or later, supporting gradual dose adjustments 4
• Monitor for emergence of mania, behavioral activation, and sexual dysfunction 2, 4

Overdose Considerations

• Most common overdose symptoms: somnolence, vomiting, tachycardia, nausea, dizziness, agitation, tremor 3
• Serious overdose effects include bradycardia, bundle branch block, coma, convulsions, QT-interval prolongation, Torsade de Pointes 3
• Sertraline has a wider safety margin than tricyclic antidepressants 5

Special Population Considerations

Adolescents and Children

• Start at 25 mg daily with slow up-titration (12.5-25 mg increments) to effective dose of 50 mg, maximum 200 mg 1
• Behavioral activation is more common in younger children than adolescents 4
• Only fluoxetine is FDA-approved for children; escitalopram is approved for adolescents ≥12 years 1

Elderly Patients

• No dosage adjustment needed based solely on age 6
• Generally well tolerated with similar adverse event profile to younger patients 6
• Lacks marked anticholinergic effects that characterize tricyclic antidepressants 6