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

Side Effects of Sertraline

Common Side Effects

The most frequently reported side effects of sertraline include gastrointestinal disturbances (nausea, diarrhea), sexual dysfunction, headache, insomnia, sweating, and tremor. 1

Gastrointestinal Effects

• Nausea occurs in approximately 24-27% of patients and is typically mild and transient, decreasing with continued treatment 2, 3
• Diarrhea or loose stools affects approximately 14% of sertraline users, which is significantly higher than other SSRIs (6.8%) 2, 3
• Dyspepsia and flatulence are also commonly reported, with flatulence occurring in up to 64% of patients in naturalistic settings 4

Sexual Dysfunction

• Male sexual dysfunction, primarily ejaculatory delay or ejaculation failure, is a prominent side effect 5, 1, 6
• Decreased libido occurs in both men and women 5, 1
• Higher doses may increase the frequency of erectile dysfunction, though studies have been too small to definitively establish this dose-response relationship 5

Neuropsychiatric Effects

• Tremor is commonly reported and can occur as a direct side effect at therapeutic doses 7, 1
• Somnolence (drowsiness) affects approximately 59% of patients 4
• Insomnia and sleep disturbances are frequent 8, 1
• Memory impairment (51%) and decreased concentration (50%) are commonly reported in naturalistic settings 4
• Fatigue affects approximately 45% of patients 8, 4

Other Common Effects

• Increased sweating occurs in 13-38% of patients 2, 4
• Headache affects 17-19% of patients 2, 4
• Dry mouth occurs in approximately 45% of patients 5, 4
• Dizziness affects 11-12% of patients 2
• Weight changes, including weight gain (45%) and decreased appetite, are reported 1, 4
• Yawning is frequent (47% in naturalistic settings) 1, 4

Serious Side Effects and Safety Concerns

Serotonin Syndrome

• Serotonin syndrome is a potentially life-threatening condition characterized by mental status changes (agitation, confusion), autonomic hyperactivity (fever, tachycardia, tachypnea, sweating), and neuromuscular abnormalities (tremor, rigidity, hyperreflexia) 5
• Risk increases dramatically when sertraline is combined with other serotonergic medications including MAOIs (contraindicated), other SSRIs/SNRIs, tramadol, triptans, lithium, St. John's Wort, tryptophan, or illicit drugs (MDMA, methamphetamine, cocaine) 5, 1
• In mild cases, symptoms include headache, nausea, sweating, and dizziness; severe cases present with hyperthermia, rigidity, delirium, and coma 5

Cardiovascular Effects

• Sertraline is essentially devoid of significant cardiovascular effects at therapeutic doses 6, 9
• However, QT-interval prolongation and Torsade de Pointes arrhythmias have been reported in overdose situations 1
• Tachycardia is common in overdose cases 1

Hepatic Effects

• Asymptomatic elevations in liver enzymes (AST/ALT) occur infrequently (approximately 0.8%) 1
• These elevations typically occur within 1-9 weeks of treatment and resolve upon discontinuation 1
• Rare cases of hepatitis, jaundice, hepatomegaly, and liver failure (potentially fatal) have been reported 1

Hematologic Effects

• Rare but serious: agranulocytosis, aplastic anemia, pancytopenia, leukopenia, and thrombocytopenia 1

Severe Skin Reactions

• Stevens-Johnson syndrome and other potentially fatal severe cutaneous reactions have been reported 1
• Photosensitivity and vasculitis can occur 1

Other Serious Effects

• Seizures or convulsions can occur, particularly in patients with a history of seizure disorders 1
• Hyponatremia (low sodium levels) is a recognized risk 1
• Bleeding complications may occur, especially when combined with aspirin, NSAIDs, or anticoagulants like warfarin 1
• Rare cases of pancreatitis have been reported 1

Discontinuation Syndrome

Sertraline is associated with discontinuation syndrome, characterized by dizziness, nausea, headache, fatigue, irritability, anxiety, insomnia, and sensory disturbances (paresthesias) 5

• This syndrome occurs following missed doses or abrupt discontinuation 5
• Sertraline has a moderate risk compared to paroxetine (highest risk) but higher than fluoxetine (lowest risk) 5
• Symptoms typically resolve within 1-2 weeks 5

Special Populations

Pregnancy and Neonatal Effects

• Third-trimester exposure causes neonatal withdrawal syndrome in newborns, presenting with continuous crying, irritability, jitteriness, tremors, hypertonia, respiratory distress, feeding difficulty, hypoglycemia, and rarely seizures 5
• Symptoms onset ranges from hours to days after birth and usually resolve within 1-2 weeks 5
• Despite these risks, SSRI treatment should be continued during pregnancy at the lowest effective dose, as untreated maternal depression poses significant risks to the mother-infant dyad 5

Breastfeeding

• Sertraline is minimally excreted in breast milk, providing the infant less than 10% of the maternal daily dose (weight-normalized) 5
• Approximately 6% of paired infant-to-maternal plasma concentration ratios exceed 0.10 5
• Mothers should be counseled about risks and benefits of breastfeeding while on sertraline 5

Children and Adolescents

• Additional side effects in pediatric populations include abnormal increase in muscle movement, agitation, nosebleeds, increased urination, urinary incontinence, aggressive reactions, and heavy menstrual periods 1
• Possible slowed growth rate and weight changes require monitoring of height and weight during treatment 1

Drug Interactions

Contraindicated Combinations

• MAOIs are absolutely contraindicated due to severe serotonin syndrome risk 5, 1

Significant Interactions

• CYP2D6 substrates: Sertraline inhibits CYP2D6, potentially increasing levels of drugs metabolized by this enzyme including propafenone, flecainide, and digitoxin 5, 1
• Anticoagulants: Warfarin levels may be altered, requiring monitoring 5, 1
• Antidiabetic agents: Tolbutamide metabolism may be affected 5, 1
• Cimetidine may increase sertraline levels 1
• Other serotonergic drugs: Exercise caution when combining with any medication that increases serotonin (start low, titrate slowly, monitor closely in first 24-48 hours after dose changes) 5

Overdose Presentation

• Most common overdose symptoms: somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor 1
• Serious overdose complications include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, QT-prolongation, serotonin syndrome, and Torsade de Pointes 1
• The largest known ingestion (13.5 grams) resulted in recovery, though fatalities have occurred with doses as low as 2.5 grams 1

Clinical Advantages

• Sertraline has minimal anticholinergic activity, avoiding dry mouth, constipation, urinary retention, and cognitive impairment typical of tricyclic antidepressants 6, 9
• No significant cardiovascular toxicity at therapeutic doses, making it safer for elderly patients and those with cardiovascular disease 6, 9
• Wide therapeutic index with better safety margin than tricyclic antidepressants 9
• No psychomotor impairment at therapeutic doses 9