What are the potential side effects of sertraline (an antidepressant medication) in adults and adolescents with a history of depression or anxiety disorders?

Sertraline Side Effects

Sertraline causes side effects in approximately 86% of patients, with most emerging within the first few weeks of treatment, requiring close monitoring especially for suicidal thinking, serotonin syndrome, and sexual dysfunction. 1

Common Side Effects (Occurring in >5% of Patients)

Gastrointestinal Effects

• Nausea is the most common side effect, occurring in 25% of patients compared to 11% with placebo 2
• Diarrhea/loose stools affect 20% of patients versus 10% with placebo 2
• Other GI effects include dry mouth (14% vs 9%), constipation (6% vs 4%), dyspepsia (8% vs 4%), and decreased appetite (6% vs 2%) 2
• These symptoms are typically mild to moderate and often transient 1, 3

Neurological and Psychiatric Effects

• Insomnia occurs in 21% of patients versus 10% with placebo, making it one of the most common side effects 2
• Somnolence affects 13% versus 7% with placebo 2
• Dizziness occurs in 12% versus 7% with placebo 2
• Headache affects 25% versus 23% with placebo 2
• Tremor occurs in 8% versus 2% with placebo 2
• Agitation affects 5% versus 3% with placebo 2
• Fatigue occurs in 12% versus 7% with placebo 2

Sexual Dysfunction

• Ejaculatory failure occurs in 14% of male patients versus 1% with placebo, representing one of the most bothersome persistent side effects 2
• Decreased libido affects 6% versus 2% overall 2
• Sexual dysfunction occurs in approximately 17% of patients and often persists throughout treatment 1

Other Common Effects

• Increased sweating affects 7% versus 2% with placebo 2
• Weight changes can occur, with both weight loss and weight gain reported 1

Serious Adverse Effects Requiring Immediate Medical Attention

Suicidal Thinking and Behavior

• All SSRIs including sertraline carry a black box warning for suicidal thinking and behavior through age 24 years 1
• The pooled absolute risk is 1% for antidepressant-treated youth versus 0.2% for placebo (number needed to harm = 143) 1, 4
• Systematic assessment for new or worsening suicidal ideation must be performed at every visit, particularly during the first few weeks of treatment and after any dose adjustments 4

Serotonin Syndrome

• Can arise within 24-48 hours after combining serotonergic medications or dose increases 1
• Characterized by mental status changes, neuromuscular hyperactivity (tremor, rigidity, myoclonus), and autonomic hyperactivity (hyperthermia, tachycardia, diaphoresis) 1, 2
• Advanced 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 hospitalization, discontinuation of all serotonergic agents, and continuous cardiac monitoring 1

Bleeding Risk

• Abnormal bleeding including ecchymosis, hematoma, epistaxis, petechiae, and hemorrhage is a rare but serious side effect 1
• Risk is especially increased with concomitant aspirin or NSAID use 1

Other Serious Effects

• Seizures are rare but serious, requiring caution in patients with seizure history 1
• Hyponatremia can occur, particularly in elderly patients who may be at greater risk 2

Discontinuation Syndrome

Abrupt cessation of sertraline can cause a discontinuation syndrome characterized by dizziness, fatigue, lethargy, headaches, nausea, vomiting, diarrhea, insomnia, anxiety, irritability, sensory disturbances, and paresthesias 5, 1

• This occurs more commonly with shorter-acting SSRIs including sertraline 5
• A brief taper rather than abrupt cessation minimizes withdrawal symptoms 1

Special Considerations in Pediatric Patients

Unique Pediatric Side Effects

• Behavioral activation/agitation (motor restlessness, insomnia, impulsiveness, disinhibited behavior, aggression) is more common in younger children than adolescents 6
• Abnormal increase in muscle movement or agitation 2
• Nose bleeds, urinating more often, and urinary incontinence 2
• Aggressive reactions 2
• Heavy menstrual periods in adolescent females 2

Growth and Weight Concerns

• Weight loss of >7% of body weight occurred in approximately 7% of children versus none with placebo 2
• In adolescents, about 2% had weight loss >7% versus 1% with placebo 2
• Regular monitoring of weight and growth is recommended if long-term treatment is continued in pediatric patients 2
• Mean weight loss of approximately 0.5 kg was seen during the first eight weeks of treatment 2

Monitoring Requirements

• Parental oversight of medication regimens is paramount in all pediatric patients 6
• At low doses, children may require twice-daily dosing due to shorter effective half-life in some pediatric patients 6

Critical Drug Interactions

Absolute Contraindications

• Concomitant administration with monoamine oxidase inhibitors (MAOIs) is absolutely contraindicated due to serotonin syndrome risk 5, 1

Significant Interactions

• Sertraline may interact with drugs metabolized by CYP2D6 5
• Caution with drugs that prolong the QT interval 5
• Other serotonergic drugs (triptans, tramadol, St. John's Wort, tryptophan) require extreme caution 2
• Warfarin and other anticoagulants may have altered effects 2
• Drugs affecting heart rhythm (propafenone, flecainide, digitoxin) require monitoring 2

Clinical Monitoring Strategy

Clinical improvement typically occurs by week 6, with maximal benefit by week 12 or later, so adequate trial duration is essential before declaring treatment failure 6, 7

• Start with a subtherapeutic "test" dose as initial adverse effects can include anxiety or agitation 5
• Increase dose as tolerated in smallest available increments at approximately 1- to 2-week intervals 5
• Higher doses are associated with more adverse effects, not necessarily better efficacy 1
• A full therapeutic trial requires 8-12 weeks at target dose before determining efficacy 1

Important Clinical Caveats

• Most adverse events are mild to moderate in severity and resolve with no action taken 7
• The safety profile of sertraline in overdose is very favorable compared to tricyclic antidepressants 8, 9
• Sertraline has low potential for pharmacokinetic drug interactions compared to other SSRIs like fluoxetine, fluvoxamine, and paroxetine 9
• Rare cases of psychosis have been reported in adolescents treated with sertraline, resolving after discontinuation 10