Do Antidepressant Drugs Worsen Seizures

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There is a widespread concern among clinicians that anti-depressant drugs can worsen seizures; such a worry is one of the more frequent causes that has limited the prescription of these drugs in PWE who suffer from a depressive disorder. Yet, a careful review of the literature shows that in the general population, an anti-depressant-related increased risk of epileptic seizures has been limited to four anti-depressant drugs: clomipramine, maprotiline, amoxepine and bupropion, and to tricyclic anti-depressant drugs at high plasma serum concentrations resulting from overdoses or encountered in individuals with a genetic predisposition to be a slow metabolizer.

In animal models of epilepsy, anti-depressant drugs that increase the synaptic concentration of serotonin and epinephrine have been found to have anti-convulsant properties. A recent study appears to confirm a 'protective' effect of SSRIs and SNRIs in depressed patients: Alper et al. compared the incidence of seizures between depressed patients randomized to placebo and SSRIs (citalopram, fluoxetine, fluvoxamine), the SNRI venlafaxine and the a2-antagonist mirtazapine in the course of regulatory studies submitted to the Food and Drug Administration (FDA) [17]. The seizure frequency among patients randomized to placebo was 1501.5 seizures/100 000 years, while that of patients randomized to the antidepressants was 534.8 seizures/100 000 years. These data clearly indicate the relatively high occurrence of seizures in depressed patients (relative to that of the general population) but it is significantly higher among patients randomized to placebo. These data raise the question of whether the seizure occurrence in depressed patients is an expression of the increased risk of developing epilepsy associated with a history of depression referred to above.

Anti-depressant drugs of the SSRI family are in general safe when used in PWE. Three open trials with SSRIs have found a decrease in seizure frequency in patients with refractory partial epilepsy and one double-blind placebo-controlled study with tricyclic anti-depressants (TCAs) found a significant reduction in absence seizures [18-20]. Finally, in a study of 100 patients with epilepsy, most of whom had pharmacoresistant epilepsy, sertraline was found to definitely worsen seizures in only one patient, while in five patients there was a transient increment in seizure frequency which subsided without any changes in dose [13]. We have used the SNRI venlafaxine in more than 100 PWE without identifying any worsening of seizure type or frequency (unpublished data).

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