What are the common and serious adverse effects of sertraline and how should they be monitored?

Sertraline Adverse Effects and Monitoring

Sertraline is generally well tolerated with most adverse effects emerging within the first few weeks of treatment, but requires vigilant monitoring for serious complications including suicidal ideation (especially in patients ≤24 years), serotonin syndrome, abnormal bleeding, and hyponatremia. 1, 2

Common Adverse Effects

The most frequently reported adverse effects in patients receiving sertraline include: 1, 3, 4

• Gastrointestinal symptoms: Nausea, diarrhea/loose stools, dry mouth, heartburn, constipation, and changes in appetite 1, 5
• Neurological effects: Headache, dizziness, somnolence, insomnia, tremor, and vivid dreams 1, 3
• Other common effects: Increased sweating (diaphoresis), fatigue, nervousness, bruxism, taste abnormalities, and weight changes (typically 1-2 pound loss) 1, 2, 3

Sexual dysfunction occurs frequently and includes decreased libido, erectile dysfunction, delayed ejaculation, and anorgasmia, though sertraline has a more favorable sexual side effect profile than paroxetine (14% ejaculatory failure and 6% decreased libido versus 70.7% overall sexual dysfunction with paroxetine). 1, 6

Pediatric-Specific Adverse Effects

In children and adolescents, additional adverse effects include: 1

• Abnormal increase in muscle movement or agitation
• Nosebleeds and urinary frequency/incontinence
• Aggressive reactions
• Heavy menstrual periods
• Possible slowed growth rate requiring height and weight monitoring 1

Serious Adverse Effects Requiring Immediate Attention

Suicidal Ideation and Behavior

All SSRIs carry an FDA black box warning for increased suicidal thinking and behavior in patients through age 24 years. 1, 2

• Pooled absolute risk: 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 dosage adjustments 1, 2

Serotonin Syndrome

This potentially life-threatening condition requires immediate medical attention and presents with: 1, 2

• High fever, uncontrolled muscle spasms, stiff muscles
• Rapid changes in heart rate or blood pressure
• Confusion, loss of consciousness
• Mental status changes, neuromuscular hyperactivity, autonomic hyperactivity 1

Risk increases with concomitant use of other serotonergic agents (MAOIs, other antidepressants, tramadol, triptans, tryptophan, St. John's Wort). 1, 2

Behavioral Activation/Agitation

More common in younger children than adolescents and typically occurs early in treatment or with dose increases: 1

• Motor or mental restlessness, insomnia, impulsiveness
• Talkativeness, disinhibited behavior, aggression
• Slow up-titration and close monitoring (particularly in younger children) are essential 1
• Usually improves quickly after dose reduction, distinguishing it from mania/hypomania which may persist and require active intervention 1

Abnormal Bleeding

SSRIs increase bleeding risk ranging from minor ecchymoses to life-threatening hemorrhage: 1, 2

• Risk amplified by concomitant use of aspirin, NSAIDs, warfarin, or other anticoagulants 1, 2
• Patients should be cautioned about this risk, especially when combining medications 2

Hyponatremia

While one study found no significant changes in serum sodium with sertraline 7, all SSRIs can cause hyponatremia through SIADH, particularly in elderly patients: 6

• Monitor serum sodium, especially in the first month of treatment 8
• Symptoms include confusion, headache, and weakness 6

Seizures

Sertraline should be introduced with care in patients with seizure disorders: 2

• Crude incidence of 0.2% observed in development programs 2
• Three of four patients who experienced seizures were adolescents, two with known seizure disorders 2

Mania/Hypomania

Occurred in approximately 0.4% of sertraline-treated patients during premarketing testing. 2 Unlike behavioral activation, mania may appear later in treatment and persist after discontinuation, requiring active pharmacological intervention. 1

Monitoring Algorithm

Initial Phase (First 2-4 Weeks)

• Weekly monitoring for suicidal ideation, especially in patients ≤24 years 1, 2
• Assess for behavioral activation/agitation (particularly in children) 1
• Monitor for common adverse effects (nausea, diarrhea, insomnia, headache) 1
• Educate patients/families in advance about potential side effects 1

Ongoing Monitoring

• Assess for sexual dysfunction at each visit, as patients rarely volunteer this information 6
• Monitor for bleeding symptoms, especially with concomitant anticoagulant/NSAID use 1, 2
• Check serum sodium if cognitive symptoms develop, particularly in elderly patients 6, 8
• Monitor height and weight in pediatric patients 1
• Reassess after dosage adjustments with same vigilance as initial treatment 1

Discontinuation Monitoring

Abrupt discontinuation can cause withdrawal symptoms including: 2

• Dysphoric mood, irritability, agitation, dizziness
• Sensory disturbances (paresthesias, electric shock sensations)
• Anxiety, confusion, headache, lethargy, emotional lability, insomnia

Gradual dose reduction is recommended whenever possible rather than abrupt cessation. 2 If intolerable symptoms occur, resume the previous dose and taper more slowly. 2

Special Populations and Precautions

Cardiovascular Disease

Sertraline has been extensively studied in patients with cardiovascular disease and appears safe: 1

• Lower risk of QTc prolongation compared to citalopram or escitalopram 1
• Post-MI trial showed no difference from placebo in cardiovascular events 2
• Lacks significant ECG abnormalities in controlled trials 2

Hepatic Impairment

Sertraline clearance is reduced in chronic mild liver impairment, resulting in increased AUC, Cmax, and elimination half-life. 2 Dose adjustment may be necessary. 2

Drug Interactions

Sertraline has minimal inhibitory effects on major cytochrome P450 enzymes, giving it advantages over paroxetine, fluoxetine, and fluvoxamine in elderly patients likely to receive multiple medications. 3, 4, 9

However, monitor for interactions with: 1, 2

• Medications metabolized by CYP450 system
• Serotonergic agents (risk of serotonin syndrome)
• Anticoagulants and antiplatelet agents (increased bleeding risk)
• Medications affecting platelet function 1

Key Clinical Pitfalls to Avoid

• Do not combine with MAOIs or use within 14 days of discontinuing MAOIs due to serotonin syndrome risk 2
• Avoid abrupt discontinuation—always taper gradually 2
• Do not assume absence of sexual dysfunction—actively inquire at each visit as it is vastly underreported 6
• Do not overlook behavioral activation in children—it is more common than in adolescents and requires slow titration 1
• Do not exceed optimal dosing—higher doses increase adverse effects without proportional benefit in many patients 1
• Monitor elderly patients for hyponatremia, especially in the first month 6, 8