What are the potential side effects of sertraline (an antidepressant) in adults or adolescents with a mental health diagnosis, particularly those with a history of liver or kidney disease?

Sertraline Side Effects

Sertraline is generally well-tolerated, but nausea and gastrointestinal symptoms are the most common side effects, along with sexual dysfunction, insomnia, sweating, and headache—with nausea being the leading cause of treatment discontinuation. 1, 2, 3

Most Common Side Effects

Gastrointestinal Effects

• Nausea and vomiting occur in 21-30% of patients and represent the most frequent reason for discontinuing sertraline. 1, 2
• Diarrhea is significantly more common with sertraline than with other SSRIs (bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, or venlafaxine). 1
• Dry mouth, constipation, heartburn, and indigestion occur frequently. 2, 3
• Loss of appetite is commonly reported. 3

Neurological and Sleep Effects

• Headache affects up to 17 per 1,000 person-months of therapy. 2
• Insomnia occurs in 16-28% of patients and is a common reason for discontinuation. 2
• Somnolence and fatigue affect 10-13% and 10-12% of patients respectively. 2
• Dizziness is frequently reported across all patient populations. 1, 2, 3
• Tremor or shaking occurs commonly. 1, 3

Sexual Dysfunction

• Sexual side effects are extremely common but likely underreported in clinical trials, are strongly dose-related, and represent a leading cause of treatment discontinuation and non-compliance. 2
• Specific manifestations include delayed ejaculation or ejaculation failure, decreased libido, anorgasmia, and erectile dysfunction. 2, 3
• Sertraline has lower rates of sexual dysfunction compared to paroxetine but higher rates than bupropion. 1

Other Common Effects

• Increased sweating affects 7-15% of patients across all age groups. 1, 2, 3
• Agitation and emotional lability can occur, particularly early in treatment. 3
• Taste abnormalities are reported. 4

Serious but Less Common Side Effects

Psychiatric and Behavioral

• SSRIs including sertraline are associated with an increased risk for nonfatal suicide attempts (odds ratio 1.57-2.25), though not completed suicide. 1
• Anxiety or agitation can paradoxically worsen initially, particularly in the first 24-48 hours after starting or dose increases. 1, 3
• Rare psychiatric effects include hallucinations, delusions, paranoid reactions, mania, and withdrawal syndrome. 3

Cardiovascular and Metabolic

• QT-interval prolongation and Torsade de Pointes arrhythmias have been reported. 3
• Hypertension and hypotension can occur. 3
• Small mean increases in total cholesterol (approximately 3%) and triglycerides (approximately 5%) may occur. 3

Hepatic

• Asymptomatic elevations in liver enzymes (AST/ALT) occur in approximately 0.8% of patients, typically within the first 1-9 weeks, and resolve with discontinuation. 3
• Rare but serious hepatic events include hepatitis, jaundice, hepatomegaly, and liver failure. 3

Hematologic and Other Serious Effects

• Rare hematologic effects include agranulocytosis, aplastic anemia, pancytopenia, leukopenia, and thrombocytopenia. 3
• Hyponatremia can occur, particularly in elderly patients. 1
• Seizures may occur, though sertraline lacks the marked seizure risk of some other antidepressants. 1, 3
• Severe skin reactions including Stevens-Johnson syndrome have been reported rarely. 3

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition that requires immediate medical attention. 3

• Concomitant use with MAOIs is absolutely contraindicated due to severe risk of serotonin syndrome. 1, 3
• Risk increases dramatically when combining sertraline with other serotonergic medications including other SSRIs/SNRIs, tricyclic antidepressants, triptans (migraine medications), tramadol and other opioids, stimulants, dextromethorphan, St. John's Wort, tryptophan, and illicit drugs (ecstasy, methamphetamine, cocaine, LSD). 1, 3
• Symptoms include high fever, uncontrolled muscle spasms, stiff muscles, rapid changes in heart rate or blood pressure, confusion, and loss of consciousness. 3

Discontinuation Syndrome

Sertraline is particularly associated with discontinuation syndrome when stopped abruptly, characterized by multiple distressing symptoms. 1, 2

• Symptoms include dizziness, fatigue, lethargy, general malaise, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, sensory disturbances, paresthesias, anxiety, irritability, and agitation. 1, 2
• Discontinuing sertraline over 10-14 days limits withdrawal symptoms. 1
• Missed doses can trigger withdrawal symptoms due to sertraline's shorter half-life. 1

Special Population Considerations

Children and Adolescents

• Additional side effects include abnormal increase in muscle movement or agitation, nose bleeds, urinating more often, urinary incontinence, aggressive reactions, and heavy menstrual periods. 3
• Possible slowed growth rate and weight changes require monitoring of height and weight during treatment. 3
• Slow up-titration and close monitoring are recommended, especially in younger children, to minimize behavioral activation and agitation. 2

Elderly Patients

• The tolerability profile is generally similar to younger patients. 4
• Sertraline lacks the marked anticholinergic effects of tricyclic antidepressants, making it a better choice for elderly patients who are particularly prone to these effects. 4
• No dosage adjustments are warranted based solely on age. 4

Patients with Liver or Kidney Disease

• Liver enzyme elevations typically occur within 1-9 weeks and resolve with discontinuation. 3
• Caution is warranted in patients with pre-existing liver problems. 3

Clinical Management Strategies

Minimizing Side Effects

• Starting with a subtherapeutic "test" dose can help identify patients who will experience anxiety or agitation as an initial adverse effect. 1
• Increase doses slowly at 1-2 week intervals for shorter half-life SSRIs like sertraline to optimize the benefit-to-harm ratio. 1
• Taking sertraline with food may reduce gastrointestinal symptoms. 3
• Most side effects are transient and diminish within the first few weeks of treatment. 5, 6

Important Drug Interactions

• Sertraline mildly inhibits CYP2D6 but has minimal effects on other cytochrome P450 isoenzymes, resulting in a comparatively low potential for drug interactions compared to paroxetine, fluoxetine, and fluvoxamine. 4, 6
• Caution with drugs metabolized by CYP2D6 (e.g., propafenone, flecainide, digitoxin). 1, 3
• Caution with drugs that prolong QT interval. 1
• Warfarin levels may be affected due to high protein binding. 3, 6

Overdose Profile

• The safety margin of sertraline is wider than tricyclic antidepressants, with a very favorable safety profile in overdose. 5, 7, 6
• The largest known ingestion was 13.5 grams with recovery, though a 2.5 gram ingestion resulted in one fatality. 3
• Most common overdose symptoms are somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor. 3