What are the side effects of Sertraline (Selective Serotonin Reuptake Inhibitor)?

Side Effects of Sertraline

Sertraline commonly causes gastrointestinal side effects (nausea, diarrhea) and sexual dysfunction, with most adverse effects emerging within the first few weeks of treatment and typically being mild and transient. 1, 2

Common Side Effects (Occurring Early in Treatment)

Gastrointestinal Effects

• Nausea is one of the most frequently reported side effects, occurring in approximately 24-27% of patients 3
• Diarrhea/loose stools occurs more commonly with sertraline than other SSRIs (14% vs 6.8%) 3
• Dry mouth, heartburn/indigestion, and loss of appetite are additional gastrointestinal complaints 1, 2
• Nausea and vomiting are the most common reasons for treatment discontinuation 1

Neurological/Psychiatric Effects

• Headache affects approximately 17-19% of patients 3
• Dizziness and somnolence (sleepiness) are common 1
• Insomnia or changes in sleep habits may occur 1, 2
• Tremor or shaking 1, 2
• Fatigue or feeling tired 1, 2

Other Common Effects

• Increased sweating/diaphoresis occurs in 11-13% of patients 1, 3
• Sexual dysfunction including decreased libido, erectile dysfunction, delayed ejaculation, and anorgasmia 1, 2
• Weight changes (loss or gain) 1
• Vivid dreams 1

Potentially Serious Side Effects Requiring Monitoring

Suicidality (FDA Black Box Warning)

• All SSRIs carry an FDA black box warning for suicidal thinking and behavior through age 24 years 1
• The pooled absolute rate for suicidal ideation is 1% with antidepressants vs 0.2% with placebo (number needed to harm = 143) 1
• Close monitoring is essential during the first months of treatment and following dosage adjustments 1
• SSRIs are associated with increased risk for nonfatal suicide attempts (odds ratio 1.57-2.25) 1

Behavioral Activation/Agitation

• Motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, and aggression 1
• More common in younger children than adolescents and in anxiety disorders compared to depressive disorders 1
• Typically occurs early in treatment (first month) or with dose increases 1
• Usually improves quickly after dose reduction or discontinuation 1

Mania/Hypomania

• Rare reports that can be difficult to distinguish from behavioral activation 1
• Tends to appear later in treatment compared to behavioral activation 1
• May persist after discontinuation and require active pharmacological intervention 1

Serotonin Syndrome

• Potentially life-threatening condition caused by elevated brain serotonin levels 1, 2
• Symptoms include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness 1
• Most commonly occurs when combining sertraline with MAOIs or other serotonergic drugs 1, 2
• Symptoms typically arise within 24-48 hours after combining medications 1

Other Serious Adverse Events

• Abnormal bleeding, especially with concomitant aspirin or NSAID use (ecchymosis, epistaxis, petechiae, hemorrhage) 1
• Seizures - use cautiously in patients with seizure history 1
• Hyponatremia (low sodium levels) 1, 2
• Rare hepatotoxicity with elevated liver enzymes, jaundice, and in extreme cases liver failure 2
• QT-interval prolongation and Torsade de Pointes arrhythmias 2

Dosing Considerations to Minimize Side Effects

• Starting at a lower dose and slowly titrating upward minimizes initial side effects 4
• At low doses, sertraline may require twice-daily dosing in youth, though most patients can use once-daily dosing 1
• The logarithmic response model shows clinically significant improvement by week 6, supporting slow up-titration to avoid exceeding optimal dose 1

Special Populations

Children and Adolescents

• Abnormal increase in muscle movement or agitation 2
• Nosebleeds and urinary frequency/incontinence 2
• Aggressive reactions 2
• Heavy menstrual periods 2
• Possible slowed growth rate and weight changes requiring monitoring 2

Overdose

• The largest known ingestion was 13.5 grams with recovery, though fatalities have occurred with as little as 2.5 grams 2
• Overdose symptoms include somnolence, vomiting, tachycardia, nausea, dizziness, agitation, tremor, and potentially seizures, coma, or cardiac arrhythmias 2
• Sertraline has a wider safety margin in overdose than tricyclic antidepressants 1, 5

Clinical Pitfalls to Avoid

• Do not combine with MAOIs or use within 14 days of MAOI discontinuation due to serotonin syndrome risk 1, 2
• Exercise caution when combining with other serotonergic drugs (tramadol, triptans, other antidepressants, dextromethorphan, St. John's Wort) 1, 2
• Educate patients and families in advance about behavioral activation and suicidality risks, particularly in younger patients 1
• Monitor for discontinuation syndrome, as sertraline (along with paroxetine and fluvoxamine) is associated with withdrawal symptoms 1