Zoloft (Sertraline) Side Effects
Zoloft is generally well-tolerated with the most common side effects being gastrointestinal disturbances, sexual dysfunction, sleep changes, and increased sweating, though serious risks including bleeding, hyponatremia, serotonin syndrome, and suicidal ideation require careful monitoring, particularly in patients with bipolar disorder, seizure history, or liver disease. 1
Common Side Effects
The typical side effects of sertraline include 2:
- Gastrointestinal symptoms: Nausea, diarrhea, indigestion, and loss of appetite
- Sexual dysfunction: Decreased libido, ejaculation failure, and other sexual problems 1, 3
- Sleep disturbances: Insomnia or increased sleepiness 1
- Neurological effects: Tremor, dizziness, headache, and increased sweating 2
- Psychiatric symptoms: Nervousness, agitation, and anxiety 2
- Fatigue and weakness 1
Real-world data indicates that approximately 38% of patients experience side effects, with sexual dysfunction, sleepiness, and weight gain being most frequently reported, though only 25% consider these "very bothersome" 3.
Serious and Life-Threatening Side Effects
Suicidal Ideation and Behavioral Changes
Monitor closely for worsening depression, suicidal thoughts, anxiety, agitation, panic attacks, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania, especially during initial treatment and dose adjustments. 1 Families and caregivers should observe for day-to-day changes, as symptoms may emerge abruptly 1.
Serotonin Syndrome
Serotonin syndrome typically presents within 24-48 hours with mental status changes, neuromuscular hyperactivity (tremor, clonus, hyperreflexia, muscle rigidity), and autonomic instability (hyperthermia, diaphoresis, tachycardia). 4 A critical pitfall is misinterpreting early symptoms as worsening depression, which can lead to inappropriate medication escalation and potentially fatal outcomes 4.
Immediately discontinue sertraline and all serotonergic medications if serotonin syndrome is suspected, and initiate hospital-based supportive care including continuous cardiac monitoring, IV fluids, and benzodiazepines. 4 Avoid combining sertraline with tramadol, trazodone, triptans, dextromethorphan, St. John's Wort, or MAOIs, as these significantly amplify risk 4, 1.
Bleeding Risk
SSRIs including sertraline increase bleeding risk ranging from ecchymoses and epistaxis to life-threatening gastrointestinal hemorrhage. 1 Concomitant use with NSAIDs, aspirin, warfarin, or other anticoagulants substantially increases this risk 1. Patients should be counseled about bleeding precautions when taking these combinations 1.
Hyponatremia
Hyponatremia may occur, often due to SIADH, with cases reported below 110 mmol/L. 1 Elderly patients and those taking diuretics or who are volume-depleted face greater risk 1. Symptoms include headache, confusion, memory impairment, weakness, and unsteadiness leading to falls; severe cases may involve hallucinations, seizures, coma, or death 1.
Seizure Risk
While sertraline itself has a relatively low seizure risk compared to other antidepressants, patients with seizure disorders require careful consideration, as SSRIs can lower seizure threshold. 2 Bupropion should specifically be avoided in patients with seizure disorders 2.
Special Population Considerations
Patients with Bipolar Disorder
In patients with bipolar disorder or mania, sertraline can precipitate manic episodes. 1 Screen for bipolar disorder history before initiating treatment, as antidepressant monotherapy may trigger mood cycling 1.
Patients with Liver Disease
Sertraline clearance is significantly reduced in patients with chronic mild liver impairment, resulting in increased drug exposure and prolonged half-life. 1 Effects in moderate-to-severe hepatic impairment are unstudied 1. Use lower or less frequent dosing in patients with any degree of liver disease. 1
Patients with Seizure History
Approach with caution in patients with seizure history or conditions that lower seizure threshold. 1 While sertraline is better tolerated than tricyclics in this regard, monitoring remains essential 2.
Discontinuation Syndrome
Abrupt cessation can cause withdrawal symptoms including anxiety, irritability, mood changes, restlessness, sleep disturbances, headache, sweating, nausea, dizziness, electric shock-like sensations, shaking, and confusion. 1 Taper sertraline over 10-14 days whenever possible rather than stopping abruptly. 2, 1
Additional Monitoring Requirements
- Hepatic function: Asymptomatic transaminase elevations occur in approximately 0.8% of patients, typically within 1-9 weeks, and resolve with discontinuation 1
- Lipid panel: Small mean increases in total cholesterol (
3%) and triglycerides (5%) 1 - Growth monitoring in children/adolescents: Height and weight should be tracked during treatment due to potential growth rate changes 1
- Visual symptoms: Eye pain, vision changes, or eye swelling/redness warrant ophthalmologic evaluation for angle-closure glaucoma risk 1
Drug Interactions
Sertraline has less effect on cytochrome P450 metabolism compared to other SSRIs, reducing drug interaction potential. 2 However, avoid concurrent use with 1:
- MAOIs (allow 2-week washout period in either direction)
- Pimozide (risk of serious cardiac arrhythmias)
- Disulfiram with liquid formulation (due to alcohol content)
Exercise caution when combining with medications affecting serotonin, bleeding risk, or cardiac conduction 1.
Pregnancy and Breastfeeding
Discuss risks and benefits of treating depression during pregnancy, as untreated depression also poses significant risks. 1 Some sertraline passes into breast milk; evaluate the optimal feeding approach with each patient 1.