Typical Side Effects of High-Dose Sertraline
High-dose sertraline commonly causes gastrointestinal disturbances (nausea, diarrhea), sexual dysfunction (ejaculatory delay, decreased libido, anorgasmia), increased sweating, and sleep disturbances, with sexual side effects and GI symptoms being particularly prominent at doses of 100 mg or higher. 1, 2
Common Dose-Related Side Effects
Gastrointestinal Effects
- Nausea, diarrhea/loose stools, dry mouth, heartburn, and constipation are the most frequently reported adverse events during sertraline use, particularly at higher doses 1
- These GI effects are typically mild to moderate and often transient, decreasing in frequency with continued treatment 3, 4
- Loss of appetite and indigestion are also common 5
Sexual Dysfunction
- Sexual problems occur in approximately 14% of males (primarily ejaculatory delay and erectile dysfunction) and 6% of females (primarily anorgasmia and decreased libido) 1, 6
- Sexual side effects typically emerge within the first few weeks of treatment 6
- Among SSRIs, sertraline has a more favorable sexual side effect profile than paroxetine (70.7% incidence) but still causes significant dysfunction 6
- If sexual dysfunction becomes problematic, switching to bupropion (8-10% sexual dysfunction rate) is the recommended first-line alternative 6
Autonomic and Neurological Effects
- Increased sweating and diaphoresis are frequently reported, particularly at higher doses 1
- Tremor or shaking is common 5
- Sleep disturbances can manifest as either insomnia or somnolence, with sertraline having a slight alerting effect in some patients, particularly at doses of 100 mg or higher 2, 5
- Headache and dizziness are frequently reported 7
Other Common Effects
- Weight changes (either gain or loss) may occur with extended use 1
- Fatigue and feeling tired are common 5
- Agitation or behavioral activation may occur, especially in younger patients and those with anxiety disorders 1
- Taste abnormalities have been reported 7
Serious Side Effects Requiring Monitoring
Psychiatric Risks
- Suicidal ideation carries a boxed warning for patients aged 24 years or younger, with a 1% incidence versus 0.2% with placebo (NNH = 143) 1
- Mania or hypomania can occur, typically appearing later in treatment and potentially persisting after discontinuation 1
- Behavioral activation characterized by motor restlessness, insomnia, impulsiveness, and aggression may develop 1
Medical Emergencies
- Serotonin syndrome is a rare but life-threatening complication requiring immediate medical attention if symptoms develop: high fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, or loss of consciousness 1, 5
- Seizures, abnormal bleeding, and QT-interval prolongation are rare but serious potential complications 1, 5
Overdose Considerations
In overdose situations (the largest known ingestion was 13.5 grams with recovery), the most common manifestations are somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor 5. More serious overdose effects can include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, serotonin syndrome, and Torsade de Pointes 5.
Important Clinical Caveats
- Perceived sedation increases at doses of 100 mg or higher, so timing of administration should be adjusted based on individual response (consider evening dosing if drowsiness occurs) 2
- Gradual tapering is essential when discontinuing sertraline to avoid withdrawal symptoms 1
- Sertraline lacks the marked anticholinergic effects and cardiovascular toxicity characteristic of tricyclic antidepressants, making it safer in elderly patients and those with cardiovascular disease 3, 4, 7
- Alcohol should be avoided while taking sertraline 5
- The drug may affect ability to drive or operate machinery until individual response is known 5