Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports.
BACKGROUND
Clinical trial data provide an approach to the investigation of the effects of psychopharmacological agents, and psychiatric disorders themselves, on seizure threshold.


METHODS
We accessed public domain data from Food and Drug Administration (FDA) Phase II and III clinical trials as Summary Basis of Approval (SBA) reports that noted seizure incidence in trials of psychotropic drugs approved in the United States between 1985 and 2004, involving a total of 75,873 patients. We compared seizure incidence among active drug and placebo groups in psychopharmacological clinical trials and the published rates of unprovoked seizures in the general population.


RESULTS
Increased seizure incidence was observed with antipsychotics that was accounted for by clozapine and olanzapine, and with drugs indicated for the treatment of OCD that was accounted for by clomipramine. Alprazolam, bupropion immediate release (IR) form, and quetiapine were also associated with higher seizure incidence. The incidence of seizures was significantly lower among patients assigned to antidepressants compared to placebo (standardized incidence ratio = .48; 95% CI, .36- .61). In patients assigned to placebo, seizure incidence was greater than the published incidence of unprovoked seizures in community nonpatient samples.


CONCLUSIONS
Proconvulsant effects are associated with a subgroup of psychotropic drugs. Second-generation antidepressants other than bupropion have an apparent anticonvulsant effect. Depression, psychotic disorders, and OCD are associated with reduced seizure threshold.
Alper
Kenneth
K
Department of Psychiatry, Comprehensive Epilepsy Center, New York University School of Medicine, New York, NY 10016, USA. kra1@nyu.edu
Schwartz
Kelly A
KA
Kolts
Russell L
RL
Khan
Arif
A
D000928:Antidepressive Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D017277:Drug Approval / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D001523:Mental Disorders / Q000188:drug therapy; D011619:Psychotropic Drugs / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012640:Seizures / Q000139:chemically induced* / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs