Is sertraline (Zoloft) associated with an increased risk of seizures?

Sertraline and Seizure Risk

Sertraline is generally associated with a low risk of seizures, but caution is warranted in patients with predisposing factors such as a history of seizures or brain damage. 1, 2, 3

Risk Assessment

• Sertraline has a relatively low seizurogenic potential compared to other antidepressants like maprotiline and clomipramine 3
• The FDA drug label notes that seizures were not observed among approximately 3000 patients treated with sertraline in the development program for major depressive disorder 1
• However, 4 out of approximately 1800 patients (0.2%) exposed during the development program for obsessive-compulsive disorder experienced seizures, with 3 of these being adolescents with either a seizure disorder or family history of seizures 1

Clinical Evidence

• A prospective study of 100 patients with epilepsy who were treated with sertraline found that only 6% experienced an increase in seizure frequency, with only 1% meeting criteria for definite causality between sertraline and seizure worsening 2
• The American College of Physicians guideline notes that evidence evaluating adverse events such as seizures with second-generation antidepressants is scarce, but should be kept in mind when treating patients 4
• Unlike bupropion, which has weak evidence indicating an increased risk for seizures, sertraline is not specifically highlighted as having this risk in major guidelines 4

Risk Factors and Considerations

• Patients with a history of seizure disorder are at higher risk and were excluded from most clinical trials 1, 3
• Concomitant medications that lower seizure threshold may increase risk, as demonstrated in a case report of post-ECT spontaneous seizures in a patient taking sertraline, bupropion, and risperidone 5
• Dose may be a factor in seizure risk with most psychotropic medications, with higher doses generally associated with greater risk 6, 3

Clinical Management

• Sertraline should be introduced with care in patients with a seizure disorder 1
• In patients with epilepsy who require sertraline, close monitoring of seizure frequency is recommended, especially during initiation and dose adjustments 2
• If seizure worsening occurs, adjustment of antiepileptic medication doses may be sufficient to return to baseline seizure frequency without discontinuing sertraline 2

Comparative Context

• Among antidepressants, bupropion has more evidence for seizure risk than sertraline 4
• Phenelzine, tranylcypromine, fluoxetine, paroxetine, sertraline, venlafaxine, and trazodone are all considered to have relatively low seizure risk compared to other antidepressants 3

Sertraline can be used safely in most patients, including the vast majority of those with epilepsy, but clinicians should remain vigilant about the small potential risk of seizures, particularly in predisposed individuals 2, 3.