Evidence-Based Reviews

Antipsychotics and seizures: What are the risks?

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Most evidence is from case reports

Other than these 2 large studies, most of the evidence addressing the relationship between the use of antipsychotics and incidence of seizures is low quality and relies on case reports or expert opinions. Older studies found that, among FGAs, seizure risk is highest with chlorpromazine and promazine, and lowest with thioridazine and haloperidol.10 As for SGAs, case reports have described seizuresassociated with the use of quetiapine, aripiprazole, risperidone, paliperidone, and olanzapine.

Quetiapine. Three case reports published between 2002 and 2010 describe generalized tonic-clonic seizures secondary to quetiapine use.11-13 In placebo-controlled trials, seizures were reported to have occurred in 1 of 951 patients receiving quetiapine compared with 3 of 319 patients receiving placebo.14

Aripiprazole. Five case reports described staring spells and tonic-clonic seizures in patients receiving 10 to 15 mg of aripiprazole.15-19 In the New Drug Application (NDA) for aripiprazole, the incidence of seizures was estimated to be .11% (1 of 926 patients) in placebo-controlled trials and .46% (3 of 859 patients) in haloperidol-controlled trials.20

Risperidone’s product labeling suggests the drug should be used with caution in patients with a history of seizures or conditions that could result in a lower seizure threshold. In Phase III placebo-controlled trials, seizures occurred in .3% of patients treated with risperidone, although in some cases, the seizures were induced by electrolyte disturbances such as hyponatremia.21 Gonzalez-Heydrich et al22 and Holzhausen et al23 found no increase in seizure activity among patients with epilepsy who were receiving risperidone. Lane et al24 published a case report of a geriatric woman who presented with a generalized tonic-clonic seizure related to rapid titration of risperidone; however, with slower titration and lower doses, she stopped having seizures without adding any antiepileptic drugs. Komossa et al25 found that risperidone is less epileptogenic than clozapine, with a relative risk of .22.

Paliperidone is the active metabolite of risperidone and does not have pharmacokinetic interactions with drugs metabolized by the cytochrome P450 (CYP) enzymes. Its labeling indicates that the drug should be used with caution in patients with a history of seizures.26 In Phase III placebo-controlled trials of paliperidone, the rate of seizures was .22%.27 Two case reports suggest close monitoring of seizure risk in patients receiving paliperidone.28,29 Liang et al29 reported that co-administration of valproic acid could mask an underlying decrease of the seizure threshold caused by antipsychotics such as paliperidone.

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