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.
Key Words
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Article info
Publication history
Published online: January 17, 2007
Accepted:
September 25,
2006
Received in revised form:
September 8,
2006
Received:
July 27,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
