What are the long-term effects of sertraline (selective serotonin reuptake inhibitor) use?

Long-Term Effects of Sertraline

Sertraline is safe and effective for long-term use, with maintenance treatment demonstrated for up to 44 weeks in depression and 28 weeks in anxiety disorders, though patients require monitoring for persistent side effects including sexual dysfunction, weight changes, and rare but serious adverse events like suicidal ideation in younger patients. 1

Duration of Long-Term Treatment

Maintenance therapy with sertraline extends well beyond acute treatment phases:

• Major depressive disorder requires several months or longer of sustained therapy beyond initial response, with efficacy maintained for up to 44 weeks at doses of 50-200 mg/day (mean 70 mg/day) 1
• PTSD treatment efficacy is maintained for up to 28 weeks following 24 weeks of initial treatment 1
• Social anxiety disorder benefits from sustained therapy for up to 24 weeks following 20 weeks of initial treatment 1
• OCD and panic disorder require several months or longer, with demonstrated benefit for up to 28 weeks in patients who responded during initial 24-52 week treatment phases 1

The FDA label emphasizes that patients should be maintained on the lowest effective dose and periodically reassessed to determine ongoing need for treatment. 1

Common Long-Term Side Effects

The most frequently reported adverse events during extended sertraline use include:

• Gastrointestinal effects: nausea, diarrhea/loose stools, dry mouth, heartburn, constipation 2, 3
• Neurological effects: headache, dizziness, somnolence, insomnia, tremor 2, 3
• Autonomic effects: sweating (including night sweats), diaphoresis 2, 4
• Sexual dysfunction: ejaculatory delay in males, erectile dysfunction, anorgasmia 2, 3
• Weight changes: potential for weight loss or gain 2, 5

Most adverse effects emerge within the first few weeks of treatment and are generally mild and transient, though some persist with continued use. 2, 6

Serious Long-Term Risks Requiring Monitoring

Suicidal ideation and behavior (ages ≤24 years):

• All SSRIs carry a boxed warning for suicidal thinking through age 24 2
• Pooled absolute rates: 1% with antidepressants vs 0.2% with placebo (risk difference 0.7%, NNH=143) 2
• Close monitoring is essential, especially during initial months and following dose adjustments 2

Behavioral activation/agitation:

• More common in younger children than adolescents and in anxiety disorders versus depression 2
• Manifests as motor/mental restlessness, insomnia, impulsiveness, disinhibited behavior, aggression 2
• May occur early in treatment, with dose increases, or with concomitant drugs inhibiting SSRI metabolism 2

Mania/hypomania:

• Rare but documented with long-term use 2
• Typically appears later in treatment compared to behavioral activation 2
• May persist after discontinuation and require active pharmacological intervention 2

Other serious but rare effects:

• Seizures (use cautiously in patients with seizure history) 2
• Abnormal bleeding, especially with concurrent NSAIDs or aspirin 2
• Serotonin syndrome (with concomitant serotonergic medications) 5, 4
• Hyponatremia, particularly in elderly patients 1

Pediatric Long-Term Considerations

Weight and growth effects in children and adolescents:

• Decreased appetite and weight loss observed in pediatric patients 1
• In 10-week trials, sertraline caused approximately 1 kg weight loss compared to slight weight gain with placebo 1
• About 7% of children had >7% body weight loss (vs 0% placebo); 2% of adolescents had >7% loss (vs 1% placebo) 1
• Weight gain normalized by week 12 in open-label extension studies 1

Critical gap in pediatric evidence:

• Regular monitoring of weight and growth is recommended if long-term treatment continues in pediatric patients 1
• Safety beyond 1 year in children/adolescents has not been systematically assessed 1
• No studies directly evaluate effects on growth, development, and maturation during chronic use 1

Geriatric Long-Term Considerations

Sertraline is well-tolerated in elderly patients with no overall differences in adverse event patterns compared to younger subjects. 1, 3

• Urinary tract infection was the only additional adverse event reported at ≥2% incidence in geriatric placebo-controlled trials 1
• Elderly patients are at greater risk for clinically significant hyponatremia with SSRIs 1
• No dosage adjustments warranted based solely on age 3
• Sertraline has advantages over TCAs due to minimal anticholinergic effects and low drug interaction potential 3

Tolerability and Safety Profile

Sertraline demonstrates superior tolerability compared to tricyclic antidepressants:

• Minimal anticholinergic activity 6, 7
• Essentially devoid of cardiovascular effects 6, 7
• Wide therapeutic index and safety margin in overdose (though deaths reported with very large ingestions) 2, 7
• Minimal inhibitory effects on major cytochrome P450 enzymes, resulting in few clinically significant drug interactions 8, 3

Pharmacokinetic Considerations for Long-Term Use

• Elimination half-life of 22-36 hours permits once-daily dosing 8
• Steady-state plasma concentrations vary widely (up to 15-fold) at usual doses of 50-150 mg/day 8
• Extensive first-pass metabolism forms N-desmethyl-sertraline, a weakly active metabolite that accumulates to greater concentrations than parent drug at steady state 8
• Steady-state achieved within approximately 1 week 7

Discontinuation Considerations

When stopping long-term sertraline therapy:

• Gradual tapering recommended to avoid withdrawal symptoms including headache, dizziness, nausea, and electric shock-like sensations 4
• At least 14 days should elapse between sertraline discontinuation and starting an MAOI 1