Side Effects of Zoloft (Sertraline)
The most common side effects of Zoloft include nausea, diarrhea, sexual dysfunction (decreased libido and ejaculation problems in men), insomnia, increased sweating, tremor, dizziness, headache, fatigue, and anxiety. 1
Common Side Effects (Occurring in ≥5% of Patients)
According to the FDA label and clinical guidelines, the following adverse effects occur most frequently 1:
Gastrointestinal Effects
- Nausea (most common reason for discontinuation)
- Diarrhea - Sertraline has a notably higher rate of diarrhea compared to other SSRIs like bupropion, citalopram, fluoxetine, paroxetine, and venlafaxine 2
- Loss of appetite
- Indigestion
Neurological Effects
- Tremor or shaking
- Dizziness (12% vs 8% placebo)
- Headache
- Insomnia (20% vs 13% placebo)
- Somnolence/sleepiness (11% vs 6% placebo)
Sexual Dysfunction
- Decreased libido (6% vs 2% placebo)
- Ejaculation failure (8% vs 1% in men) 1
- Erectile dysfunction (4% vs 1% in men)
- Delayed or absent orgasm in women
Important caveat: Sexual dysfunction rates are likely underreported because patients and providers are often reluctant to discuss these symptoms 2. Bupropion has significantly lower rates of sexual side effects than sertraline and may be considered as an alternative if sexual dysfunction becomes problematic 2.
Other Common Effects
- Increased sweating/hyperhidrosis (7% vs 3% placebo)
- Fatigue (12% vs 8% placebo)
- Agitation (8% vs 5% placebo)
Serious Adverse Events (Less Common but Important)
Suicidality Risk
SSRIs including sertraline are associated with an increased risk of nonfatal suicide attempts (odds ratio 1.57-2.25 compared to placebo), though not completed suicide 2. This risk requires close monitoring, particularly when initiating treatment or changing doses.
Cardiac Effects
- QTc prolongation - Cases of QTc prolongation and Torsade de Pointes have been reported post-marketing 1
- Rare cases of ventricular tachycardia 3 and sinus arrest 4 have been documented
- Use caution in patients with cardiac risk factors
Other Serious Effects to Monitor
- Serotonin syndrome (when combined with other serotonergic drugs)
- Increased bleeding risk (especially with NSAIDs or anticoagulants)
- Hyponatremia (particularly in elderly patients)
- Seizures (rare)
- Angle-closure glaucoma
- Activation of mania/hypomania in bipolar patients
Pediatric-Specific Side Effects
In children and adolescents, additional common side effects include 1:
- Abnormal increase in muscle movement or agitation
- Nosebleeds
- Urinary incontinence
- Aggressive reactions
- Possible slowed growth rate and weight changes (height and weight should be monitored)
Weight and Metabolic Effects
Sertraline causes less weight gain than paroxetine or mirtazapine 2, making it a relatively favorable choice when weight concerns are present.
Discontinuation Syndrome
Abrupt discontinuation can cause withdrawal symptoms. The FDA label warns about neonatal withdrawal in babies born to mothers taking sertraline during pregnancy 1.
Clinical Context
Real-world data suggests that approximately 38% of patients report experiencing side effects from SSRIs, though only 25% consider them "very bothersome" or "extremely bothersome" 5. Notably, only 40% of patients who experience side effects mention them to their physicians 5, highlighting the importance of proactive inquiry about tolerability.
The tolerability profile is generally similar across age groups, though elderly patients may be at higher risk for hyponatremia and should be monitored accordingly 6.
Practical Management Points
- Most side effects are dose-related and may improve with time or dose adjustment
- Nausea and diarrhea often diminish after the first few weeks
- Sexual dysfunction tends to persist and may require switching medications if problematic
- Always inquire specifically about sexual function, as patients rarely volunteer this information 1
- The oral solution contains 12% alcohol and should not be used with disulfiram 1