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


Background — 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.

Methods — 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.

Results — 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.

Conclusions — 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.



Finkelstein Y, Macdonald EM, Li P, Mamdani MM, Gomes T, Juurlink DN. Clin Toxicol. 2018; 56(12):1179-84. Epub 2018 Jul 10.

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