What are the side effects of Zoloft (sertraline)?

Zoloft (Sertraline) Side Effects

Zoloft commonly causes gastrointestinal symptoms (especially nausea and diarrhea), sexual dysfunction, sleep disturbances, and neurological effects, with most side effects emerging within the first few weeks of treatment. 1

Common Side Effects (Occurring in ≥5% of Patients)

Gastrointestinal Effects

• Nausea (24% of patients) - the most frequent adverse effect and leading cause of discontinuation 2, 1
• Diarrhea/loose stools (14-64% depending on study) - notably, sertraline has a higher rate of diarrhea than other SSRIs including bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, or venlafaxine 2
• Decreased appetite (7%) 1
• Indigestion/dyspepsia 1

Sexual Dysfunction

• Ejaculation failure (8% in men) 2, 1
• Decreased libido (6-7% overall; 7% in men, 4% in women) 2, 1
• Erectile dysfunction (4% in men) 1
• Ejaculation disorder (3% in men) 1
• Delayed or absent orgasm in women 1

Important caveat: Sexual dysfunction rates are likely underreported in clinical trials, as patients and providers may be reluctant to discuss these symptoms 2, 1

Neurological Effects

• Tremor or shaking (9%) 2, 1
• Dizziness (11-12%) 2, 1
• Headache (19%) 2, 1
• Somnolence (11%) 2, 1

Sleep Disturbances

• Insomnia (20%) 2, 1
• Changes in sleep habits including increased sleepiness 1

Other Common Effects

• Increased sweating/hyperhidrosis (7-13%) 2, 1
• Fatigue (12%) 2, 1
• Agitation (8%) 2, 1
• Anxiety 1
• Dry mouth 2

Serious Adverse Effects Requiring Monitoring

Suicidality

• All SSRIs, including Zoloft, carry an FDA boxed warning for suicidal thinking and behavior through age 24 years 2, 1
• The risk for nonfatal suicide attempts increases with SSRIs (odds ratio 1.57-2.25 compared to placebo) 2
• Close monitoring is essential, especially in the first months of treatment and following dosage adjustments 2

Behavioral Activation/Agitation

• Motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, aggression 2
• More common in younger children than adolescents and in anxiety disorders compared to depressive disorders 2
• Typically occurs early in treatment (first month) or with dose increases 2
• Usually improves quickly after dose decrease or discontinuation 2

Mania/Hypomania

• Rare but can occur, particularly in patients with undiagnosed bipolar disorder 2
• May appear later in treatment compared to behavioral activation 2
• May persist and require active pharmacological intervention, unlike behavioral activation 2

Serotonin Syndrome

• A potentially life-threatening condition that must be kept in mind, particularly with concomitant use of other serotonergic agents 2, 1
• Symptoms include high fever, rapid changes in heart rate or blood pressure, uncontrolled muscle spasms, confusion, stiff muscles, loss of consciousness 1

Other Serious Effects

• Seizures - use cautiously in patients with seizure history 2, 1
• Abnormal bleeding - especially with concomitant NSAIDs or aspirin 2
• Hyponatremia 2
• QTc prolongation - use with caution in patients with risk factors 1
• Angle-closure glaucoma 1

Pediatric-Specific Side Effects

In children and adolescents, additional common side effects include 1:

• Abnormal increase in muscle movement or agitation
• Nose bleeds
• Urinary incontinence
• Aggressive reaction
• Possible slowed growth rate and weight change - height and weight should be monitored during treatment 1

Discontinuation and Withdrawal

• Nausea and vomiting are the most common reasons for discontinuation in efficacy studies 2
• Overall discontinuation rate due to adverse events: approximately 12% (compared to 4% with placebo) 1
• Abrupt discontinuation may cause withdrawal reactions 2

Clinical Considerations

Timing of Side Effects

• Most adverse effects emerge within the first few weeks of treatment 2
• Many side effects are mild and transient, decreasing in frequency with continued treatment 3, 4

Comparative Profile

• Sertraline has less weight gain than mirtazapine or paroxetine 2
• Sertraline has lower rates of sexual dysfunction than paroxetine 2
• Sertraline has a wider safety margin in overdose than tricyclic antidepressants 2

Dosing Considerations

• At low doses of sertraline, twice-daily dosing may be required in youth 2
• Slow up-titration is recommended to avoid behavioral activation and unintentionally exceeding the optimal dose 2

Important Warnings

• Do not drink alcohol while taking Zoloft 1
• May cause sleepiness or impair decision-making - avoid driving or operating heavy machinery until effects are known 1
• The oral solution contains 12% alcohol and is contraindicated with disulfiram (Antabuse) 1