The risk of seizures in patients taking antidepressant drugs depends on three factors:41–44
the intrinsic epileptogenic or antiepileptic potential of the antidepressant42
the amount of active drug that enters the brain, which depends on the dose, pharmacokinetics, and transport across the blood-brain barrier, the patient’s seizure threshold, which depends on genetic factors, remote brain injury, previous febrile or acute symptomatic seizures, and use of alcohol or other substances...
...The overall incidence of seizures in patients taking antidepressants at reasonable doses and presumed therapeutic ranges is 0.1–4.0%; this can be compared to an incident seizure risk of 0.073–0.086% in the general population of Rochester, Minnesota.41 By class of drug, the highest risk of seizures has been reported with:
the heterocyclic antidepressant clomipramine (0.5% incidence, up to 2.1% with doses of 350 mg per day or greater)
the dopamine- or norepinephrine-specific reuptake inhibitor bupropion (0.4%, up to 2.2% with doses higher than 450 mg per day)
the quaternary antidepressant maprotiline (0.4%)
The tricyclic antidepressants (TCAs) have the next highest seizure risk (which is increased by toxic levels). The newer selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, sertraline, fluvoxamine, citalopram, and paroxetine—and serotonin receptor modulators—trazodone and nefazodone—are intermediate in risk, as is venlafaxine, a combined norepinephrine and serotonin reuptake inhibitor. The monoamine oxidase inhibitors (MAOIs) carry the least risk.