Does sertraline (Selective Serotonin Reuptake Inhibitor) lower the seizure threshold?

From the Guidelines

Sertraline can lower the seizure threshold, particularly in patients with a history of seizure disorders, and should be used cautiously in such cases. The risk of seizures associated with sertraline is considered low at therapeutic doses, but it increases with higher doses, in overdose situations, or in patients with pre-existing neurological conditions 1. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders, seizures have been observed in the context of SSRI use, including sertraline, and therefore, these medications should be used cautiously in patients with a history of a seizure disorder 1.

Key Considerations

• The mechanism behind sertraline's effect on seizure threshold involves its impact on neurotransmitter systems, particularly serotonin, which can influence neuronal excitability.
• Patients with a history of seizures, those taking other medications that lower seizure threshold, or those with electrolyte abnormalities should use sertraline with caution.
• If a patient with seizure risk factors requires antidepressant treatment, sertraline may still be used but with careful monitoring, gradual dose titration, and possibly at lower target doses.
• Any new-onset seizure activity in a patient taking sertraline should prompt immediate medical evaluation.

Monitoring and Precautions

• Close monitoring for suicidality is recommended, especially in the first months of treatment and following dosage adjustments 1.
• Behavioral activation/agitation, mania/hypomania, and sexual dysfunction are potential side effects of sertraline that require careful monitoring 1.
• Serotonin syndrome, a potentially life-threatening condition, can occur when serotonergic medications are combined, and symptoms can arise within 24 to 48 hours after combining medications 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%. Three of these patients were adolescents, two with a seizure disorder and one with a family history of seizure disorder, none of whom were receiving anticonvulsant medication. Accordingly, sertraline should be introduced with care in patients with a seizure disorder

The answer to whether sertraline lowers seizure threshold is not directly stated in the label. However, it can be inferred that sertraline may have a potential to lower seizure threshold in certain patients, particularly those with a pre-existing seizure disorder, as it should be introduced with care in these patients. The label also reports a crude incidence of 0.2% of seizures in patients exposed to sertraline during the development program for obsessive-compulsive disorder. 2

From the Research

Sertraline and Seizure Threshold

• Sertraline, an antidepressant, may lower the seizure threshold, although the magnitude of this effect is not clearly established 3.
• Studies have reported that the incidence of seizures in patients treated with therapeutic doses of antidepressants, including sertraline, ranges from 0.1 to 1.5% 3.
• Sertraline is considered to have a relatively low risk of inducing seizures compared to other antidepressants, such as maprotiline and clomipramine 3.
• A study found that 6% of patients with epilepsy experienced an increase in seizure frequency after starting sertraline, although the drug can be safely used in the vast majority of patients with epilepsy 4.

Factors Influencing Seizure Risk

• The risk of seizures triggered by psychotropic drugs, including sertraline, is influenced by the individual's inherited seizure threshold and the presence of seizurogenic conditions, such as a history of epilepsy or brain damage 3.
• The dose of sertraline may also play a role in seizure risk, with higher doses potentially increasing the risk of seizures 4.

Clinical Use of Sertraline

• Sertraline is a selective serotonin reuptake inhibitor that is effective in the treatment of depression, anxiety disorders, and obsessive-compulsive disorder 5, 6.
• It has a good tolerability profile and is relatively safe in overdose, with a low risk of fatal toxicity 7, 6.