Second-generation anti-depressants and risk of new-onset seizures in the elderly

Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants.

We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index.

We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk.

The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.