What are the side effects of Zoloft (sertraline)?

Zoloft (Sertraline) Side Effects

Zoloft causes common gastrointestinal and neurological side effects that are typically mild and transient, but carries serious risks including suicidal thinking (especially in patients under 25), serotonin syndrome, and behavioral activation that require close monitoring.

Common Side Effects

The most frequently reported adverse effects with sertraline include:

Gastrointestinal Effects

• Nausea, diarrhea, loss of appetite, and indigestion are among the most common side effects, typically emerging within the first few weeks of treatment 1
• Dry mouth and heartburn may also occur 2

Neurological Effects

• Headache, dizziness, tremor, and somnolence are commonly reported 2, 1
• Insomnia or changes in sleep habits can occur 1
• Vivid dreams and fatigue may develop 2

Other Common Effects

• Increased sweating (diaphoresis) is frequently reported 2, 1
• Sexual dysfunction including decreased libido, ejaculatory delay/failure, erectile dysfunction, and anorgasmia can occur, particularly in adolescents and adults 2, 1
• Weight changes (loss or gain) and changes in appetite 2
• Nervousness and agitation 2

Serious Adverse Effects Requiring Immediate Attention

Suicidal Thinking and Behavior

• All SSRIs including sertraline carry an FDA boxed warning for increased suicidal thinking and behavior in patients through age 24 years 2
• The pooled absolute rate for suicidal ideation 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 dosage adjustments 2

Serotonin Syndrome

• This potentially life-threatening condition requires immediate medical attention and presents with: high fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, and loss of consciousness 1
• Risk increases when sertraline is combined with other serotonergic medications (triptans, other SSRIs/SNRIs, tramadol, St. John's Wort, tryptophan) 1
• Tremor can be an early warning sign of serotonin syndrome when combined with mental status changes and autonomic instability 3

Behavioral Activation/Agitation

• Motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, and aggression may occur early in treatment or with dose increases 2
• More common in younger children than adolescents and in anxiety disorders compared to depressive disorders 2
• Usually improves quickly after dose reduction or discontinuation 2

Mania/Hypomania

• Rare reports of mania or hypomania can occur, typically appearing later in treatment than behavioral activation 2
• Unlike behavioral activation, mania may persist after discontinuation and require active pharmacological intervention 2

Other Serious Effects

• Abnormal bleeding, especially with concomitant use of aspirin or NSAIDs 2, 1
• Seizures have been observed; use cautiously in patients with seizure history 2
• Severe skin reactions including Stevens-Johnson syndrome (potentially fatal) 1
• Liver toxicity with elevated enzymes, jaundice, hepatitis, and rare cases of liver failure 1
• Cardiac effects including QT-interval prolongation and Torsade de Pointes arrhythmias 1
• Hyponatremia (low sodium levels) 1

Special Population Considerations

Children and Adolescents

• Additional side effects include: abnormal increase in muscle movement, agitation, nosebleed, increased urination, urinary incontinence, aggressive reaction, heavy menstrual periods, and possible slowed growth rate 1
• Height and weight should be monitored during treatment 1
• Younger children are at higher risk for behavioral activation than adolescents 2

Pregnancy and Breastfeeding

• Third-trimester exposure may cause neonatal complications including continuous crying, irritability, jitteriness, tremors, feeding difficulties, respiratory distress, and sleep disturbance 4
• Sertraline passes into breast milk 1

Overdose

• The most common overdose symptoms are somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor 1
• Serious overdose effects include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, pancreatitis, QT-prolongation, serotonin syndrome, and Torsade de Pointes 1
• Deaths have been reported following very large ingestions despite sertraline's greater margin of safety compared to tricyclic antidepressants 2

Important Drug Interactions

Avoid or use extreme caution with:

• MAOIs (contraindicated due to serotonin syndrome risk) 1
• Other serotonergic medications (triptans, SSRIs, SNRIs, tramadol, St. John's Wort, tryptophan) 1
• Blood thinners (warfarin, aspirin, NSAIDs) increase bleeding risk 1
• Medications metabolized by CYP2D6 (tricyclics, propafenone, flecainide) 1

Clinical Monitoring Recommendations

• Most adverse effects emerge within the first few weeks of treatment 2
• Monitor closely for suicidality, especially in the first months and after dose changes 2
• Watch for behavioral activation, particularly in younger children, with slow up-titration recommended 2
• Assess for serotonin syndrome features when tremor develops, especially with polypharmacy 3
• If isolated mild tremor occurs, consider dose reduction or reassurance with continued monitoring 3