Seizure Risk Associated With Antidepressant Treatment Among Patients With Depressive Disorders: A Population-Based Case-Crossover Study

J Clin Psychiatry. 2017 Nov/Dec;78(9):e1226-e1232. doi: 10.4088/JCP.16m11377.


Objective: To assess the risk of seizure associated with antidepressant use among patients with depressive disorders.

Methods: Individuals visiting the emergency department or hospitalized because of new-onset seizure (ICD-9-CM diagnostic code 345 or 780.3; our primary study outcome) after receiving antidepressants for depressive disorders, were identified from a Taiwanese total population health insurance database. Using a case-crossover study design, relative risk of antidepressant-related seizure was estimated by comparing the rates of antidepressant exposure during the case periods vs control periods. The effects of class and dose of antidepressant on seizure risk were explored, using a conditional logistic regression model adjusting for concomitant medications. Several sensitivity analyses were conducted to attest the results of primary analyses.

Results: A total of 10,002 patients were included between 2002 and 2012. Overall, antidepressant exposure was positively associated with increased seizure risk (OR = 1.48, 95% CI, 1.33-1.64). Among the antidepressants, the increases in seizure risk of bupropion (OR = 2.23, 95% CI, 1.58-3.16), selective serotonin reuptake inhibitors (OR = 1.76, 95% CI, 1.55-2.00), serotonin and norepinephrine reuptake inhibitors (OR = 1.40, 95% CI, 1.10-1.78), and mirtazapine (OR = 1.38, 95% CI, 1.08-1.77) showed clear dose-response effects. Furthermore, the seizure risk was highest among patients aged between 10 and 24 years and patients with major depression. The results of sensitivity analyses largely confirmed those from the primary analyses.

Conclusions: The seizure-inducing propensity and dose-response relationship pattern, as well as potential risk factors, associated with individual antidepressants should be taken into consideration when choosing antidepressants during clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Case-Control Studies
  • Child
  • Cross-Over Studies
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Seizures / chemically induced*
  • Seizures / etiology
  • Young Adult


  • Antidepressive Agents