Can sertraline (Zoloft) increase the risk of seizures?

From the Guidelines

Sertraline (Zoloft) can increase the risk of seizures, particularly in patients with a history of seizure disorders or those taking other medications that lower the seizure threshold 1.

Key Points to Consider

• The risk of seizures is a potential adverse effect of sertraline, as with other SSRIs, and should be considered when prescribing this medication 1.
• Patients with a history of seizure disorders should be closely monitored when initiating or adjusting sertraline therapy 1.
• The risk of seizures may be dose-dependent, although the exact dose threshold is not well established 1.
• Other medications that lower the seizure threshold, such as certain antipsychotics, may increase the risk of seizures when co-administered with sertraline 1.
• Close monitoring and careful consideration of the potential risks and benefits are essential when prescribing sertraline to patients at risk of seizures 1.

From the FDA Drug Label

Sertraline has not been evaluated in patients with a seizure disorder. These patients were excluded from clinical studies during the product’s premarket testing. No seizures were observed among approximately 3000 patients treated with sertraline in the development program for major depressive disorder However, 4 patients out of approximately 1800 (220 <18 years of age) exposed during the development program for obsessive-compulsive disorder experienced seizures, representing a crude incidence of 0. 2%.

Accordingly, sertraline should be introduced with care in patients with a seizure disorder

Seizure Risk with Sertraline:

• Sertraline may increase the risk of seizures, particularly in patients with a pre-existing seizure disorder.
• The incidence of seizures in patients treated with sertraline for obsessive-compulsive disorder was 0.2%.
• Patients with a seizure disorder should be introduced to sertraline with caution 2.

From the Research

Seizure Risk Associated with Sertraline

• The risk of seizures associated with sertraline (Zoloft) is a concern, and several studies have investigated this relationship 3, 4, 5, 6.
• A study published in 2017 found that SSRIs, including sertraline, did not appear to worsen seizure frequency in patients with epilepsy, and may even be associated with a decrease in seizure frequency 3.
• Another study published in 2013 noted that SSRIs, including sertraline, can cause serotonin syndrome, which can manifest as seizures, but this is typically seen in cases of overdose 4.
• A 2021 review of SSRIs for stroke recovery found that SSRIs, including sertraline, may slightly increase the risk of seizures (RR 1.40,95% CI 1.00 to 1.98) 5.
• A population-based case-crossover study published in 2017 found that antidepressant exposure, including SSRIs like sertraline, was positively associated with increased seizure risk (OR = 1.48,95% CI, 1.33-1.64) 6.
• A 2022 review of the risk of fatal arrhythmias associated with sertraline in patients with post-myocardial infarction depression did not specifically address the risk of seizures, but noted that sertraline has a comparatively preferable safety profile to other SSRIs like citalopram 7.

Key Findings

• The evidence suggests that sertraline may be associated with a slight increase in seizure risk, particularly in patients with a history of epilepsy or those taking high doses of the medication 3, 5, 6.
• However, the overall risk of seizures associated with sertraline is still considered to be relatively low, and the medication is generally considered to be safe and effective for the treatment of depression and other conditions 3, 7.