New antidepressant drugs and seizures

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All of the SSRIs have been associated with seizures in clinical practice, although there is some evidence which suggests that they may have less seizure potential than the earlier agents.

Krijzer et al. (1984), used freely moving rats implanted with subcortical electrodes. Almost all of the antidepressants tested caused epileptogenic EEG changes; mianserin was the most potent. However, fluvoxamine caused only minimal effects.

None of the newer agents have been tested in such models and clinical information is largely derived from the clinical trials and postmarketing surveys. Generally the figures for seizure incidence given for all of these new compounds are less than for the tricyclics, the lowest figures being recorded so far for mirtazapine and nefad-azone.

Citalopram has been used in depression in patients with epilepsy; no change of seizure frequency was noted in 16 patients in an open study (Specchio et al., 1999). In another study, Hovorka et al. (2000) gave citalopram to 43 patients with epilepsy and comorbid depression, and assessed them over an 8-week period. Sixty-five per cent were judged to be responders to the antidepressant effect. No change of seizure frequency was noted, and no de novo generalized tonic-clonic seizures were observed.

The SSRI most used in patients with epilepsy is paroxetine. Blumer (1997; Chapter 8) has reported on the effective use of paroxetine in the management of patients with what he refers to as the interictal dysphoric disorder of epilepsy. In his studies, paroxetine is often given in combination with a tricyclic antidepressant. He reports this combination to be safe and efficacious in this population. Exacerbation of seizures was not reported, and dysphoric symptoms resolved in the majority of his cases.

We have observed three patients with persistent epilepsy who have become seizure-free on paroxetine. In one, the effect was short-lived, but in the other two the effect has been sustained. This in spite of no changes to the anticonvulsant prescriptions.

The other SSRI recently evaluated in epilepsy is sertraline (Kanner et al., 2000). They prospectively evaluated the effect of this antidepressant in 100 consecutive patients with epilepsy and depression (n = 97) or obsessive-compulsive disorder (n = 3). They noted an increase in seizures following start of therapy in 6% of patients, patients being assessed from 0.2 to 38 months. Interestingly, the mean dose of sertraline in these six was lower than in the other patients. They reported that depressive symptoms resolved in 54% of patients, but also described (Blumer, 1997) the pleomorphic clinical picture of these patients, and the symptom differences from typical major affective disorder.

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