What are the potential side effects of sertraline (Zoloft) in patients, particularly those with a history of bleeding disorders or taking anticoagulant medications?

Sertraline Side Effects

Sertraline is generally well tolerated with common gastrointestinal and sexual side effects, but carries critical warnings for bleeding risk (especially with anticoagulants), suicidal ideation in patients ≤24 years, and requires close monitoring during initiation and dose changes. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea, diarrhea, dry mouth, heartburn, and constipation are the most frequently reported adverse effects, typically emerging within the first few weeks of treatment 1
• These effects are generally mild to moderate and often transient 3
• Loss of appetite may occur, though average weight changes are minimal (1-2 pounds) 2

Sexual Dysfunction

• Ejaculatory delay in males, erectile dysfunction, and anorgasmia are common and may persist with long-term use 4
• Sexual problems including decreased libido and ejaculation failure occur frequently 2

Neurological and Autonomic Effects

• Headache, dizziness, tremor, and sweating/diaphoresis are commonly reported 1, 5
• Insomnia or somnolence may occur, with sleep disturbances being dose-dependent 1, 2
• Fatigue and nervousness are frequent complaints 2

Other Common Effects

• Taste abnormalities and vivid dreams may develop 1, 5
• Bruxism (teeth grinding) has been reported 1

Serious Side Effects Requiring Immediate Attention

Bleeding Risk - Critical for Patients on Anticoagulants

• SSRIs including sertraline increase bleeding risk ranging from ecchymoses and epistaxis to life-threatening gastrointestinal and intracranial hemorrhage 2
• The risk is significantly potentiated when combined with NSAIDs, aspirin, warfarin, or other anticoagulants 1, 2, 6
• Patients with bleeding disorders or on anticoagulant therapy require heightened vigilance and should be counseled about recognizing bleeding symptoms 2
• Case reports document spontaneous bleeding complications including periorbital purpura during sertraline treatment 7

Suicidal Ideation and Behavior

• All SSRIs carry a boxed FDA warning for increased suicidal thinking and behavior in patients through age 24 years 1
• The absolute risk is 1% with antidepressants versus 0.2% with placebo (risk difference 0.7%, NNH = 143) 1
• Close monitoring is mandatory during the first months of treatment and following any dose adjustments 1, 2

Behavioral Activation/Agitation

• Motor or mental restlessness, insomnia, impulsiveness, disinhibited behavior, and aggression may occur, particularly in younger children and those with anxiety disorders 1
• This effect is more common early in treatment or with dose increases, supporting the need for slow up-titration 1
• Concomitant drugs that inhibit sertraline metabolism can exacerbate this risk 1

Mania/Hypomania

• Hypomania or mania occurred in approximately 0.4% of sertraline-treated patients during premarketing trials 2
• Unlike behavioral activation which resolves quickly with dose reduction, mania may persist after discontinuation and require active treatment 1

Serotonin Syndrome

• Life-threatening serotonin syndrome can occur, particularly with concomitant serotonergic agents (triptans, other SSRIs/SNRIs, tramadol, tryptophan, St. John's Wort) 4, 2
• Symptoms include high fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, and loss of consciousness 2
• Requires immediate medical attention 2

Seizures

• Four patients out of approximately 1,800 exposed during OCD development programs experienced seizures (0.2% incidence) 2
• Sertraline should be introduced with care in patients with seizure disorders 2

Other Serious Effects

• Abnormal bleeding events are documented in post-marketing surveillance 2
• Rare but serious skin reactions including Stevens-Johnson syndrome 2
• Hepatotoxicity with elevated liver enzymes, jaundice, and rare cases of liver failure 2
• Hyponatremia (low sodium levels) may occur 2

Discontinuation Syndrome

• Abrupt discontinuation can cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances (electric shock sensations), anxiety, confusion, headache, and emotional lability 2
• Gradual dose reduction over 10-14 days is essential to minimize withdrawal symptoms 1, 4, 2
• If intolerable symptoms occur, resume the previous dose and taper more gradually 2

Special Populations and Considerations

Hepatic Impairment

• Sertraline clearance is reduced in patients with chronic mild liver impairment, resulting in increased drug exposure 2
• Lower or less frequent dosing is required in patients with liver disease 2

Cardiac Patients

• Sertraline was evaluated in 372 patients with recent myocardial infarction or unstable angina and showed no adverse cardiovascular effects compared to placebo 2
• The drug is not associated with significant ECG abnormalities 2

Drug Interactions

• Sertraline has less effect on metabolism of other medications compared to other SSRIs, making it advantageous in elderly patients on multiple medications 1, 5
• However, caution is needed with drugs metabolized by CYP2D6 8
• Avoid combining with MAO inhibitors, pimozide, or other drugs that prolong QT interval 2

Weight and Metabolic Effects

• Minimal weight changes (1-2 pounds on average) distinguish sertraline from other antidepressants 2
• Sertraline is associated with weight loss in short-term use and weight neutrality in long-term use, unlike paroxetine which causes significant weight gain 1

Monitoring Recommendations

• Monitor for suicidal ideation, especially in the first months and after dose changes 1, 2
• Counsel patients on bleeding risk and instruct them to report unusual bleeding or bruising 2
• Watch for behavioral activation, particularly in younger children during the first month of treatment 1
• Assess for serotonin syndrome symptoms when combining with other serotonergic agents 2
• Monitor liver function if hepatic impairment is present 2