Is any antipsychotic drug preferable to a patient with epilepsy?/nA 47-year-old woman has epilepsy

Fråga: Is any antipsychotic drug preferable to a patient with epilepsy? A 47-year-old woman has epilepsy post-op meningioma seven years ago. She is seizure-free on carbamazepine (Tegretol) 200 mg b.i.d. She now has developed a paranoid psychosis and has previously been treated for this condition without neuroleptics. This time, though, antipsychotics are presumably needed.

Sammanfattning: There are no comparative studies on the ability of antipsychotic drugs to cause seizures. Data from observational studies suggest haloperidol and risperidone to be the least seizurogenic antipsychotics. Slow dose titration is recommended. Therapeutic drug monitoring (TDM) of both the antipsychotic and the antiepileptic is mandatory.

Svar: The association between antipsychotic medication and seizures has been known for 50 years, first recognized for chlorpromazine (1). Up to 35% of drug-induced seizures are associated with psychotropic drugs (1,2). The risk of seizures associated with classic antipsychotic drugs (APD:s) is higher in patients with rapid dose-escalation and high doses, ranging from 0.3% to 9% (2).

Of classic antipsychotics, the risk of seizures is highest with chlorpromazine, lower with tricyclic APD:s (e.g. chlorprothixene) and lower still with butyrophenones (e.g. haloperidol) (2).

For atypical APD:s, data are scarcer due to lesser time on the market. In premarketing trials, the incidence of seizures was 0.3% for risperidone, 0.9% for olanzapine and quetiapine, and 3.5% for clozapine. Postmarketing studies of clozapine have shown a lower incidence (1.3%) without dose dependency (2).

Koch-Stoecker estimates the seizure risk of risperidone to be negligible, of olanzapine to be low and of haloperidol to at least be lower than for phenothiazines (2). An overview of later date, though, reviews several case reports of seizures associated with olanzapine after switching from haloperidol and zuclopenthixol, respectively, in patients with a previous history of seizures, but who had been seizure-free on the classic APD:s (1). There are also case-reports of seizures in olanzapine-treated patients with no previous history of seizures (1).

It should also be noted that there will be pharmacokinetics interactions between antiepileptics and antipsychotics. Mainly there will be an induction of the metabolism of the antipsychotic drug when co-administered with an antiepileptic, but some antipsychotics may influence the metabolism of some antiepileptics, making the net effect hard to predict (4).