Which neuroleptics have the least tendency to lower seizure threshold?

Fråga: Which neuroleptics have the least tendency to lower seizure threshold?

Sammanfattning: There is a lack of well-performed comparative studies concerning this question. According to review articles, drugs such as haloperidol, piperidine and piperazine phenothiazines seem to carry a lower risk for inducing seizures than aliphatic phenothiazines. If possible, avoidance of polypharmacy, high doses of neuroleptics and abrupt changes in the dosages, may help to minimize seizure precipitation in predisposed patients.

Svar: This question has been answered by the Drug Information Center before (1,2,3). In general, all neuroleptics can potentially induce seizures, especially when given in high doses; in polypharmacy, after abrupt change of dosage; when administered to patients with pre-existing organic brain damage; or during withdrawal from alcohol, barbiturates or benzodiazepines (4). The tenor of the previous Drug Information documents and of (review) articles dealing with this question is that well-performed comparative studies with respect to the seizure-inducing potency of neuroleptics are lacking and most information is anecdotal.

The incidence of seizures is reported to be between 0.5 per cent and 1.2 per cent (4). Clozapine has been reported to cause seizures in 2.8 per cent of patients (5). According to (6), chlorpromazine is the antipsychotic agent most commonly associated with the occurrence of seizures. A 0.3-5 per cent incidence of seizures in patients without a history of epilepsy treated with low to moderate doses of chlorpromazine (30-900 mg/day) has been reported. However, it is unclear whether (and to what extent) this actually reflects a higher potential for inducing seizures or its more frequent use, including the initial use of higher doses when the drug was introduced (6). Thioridazine, pimozide, fluphenazine and haloperidol appear to be the agents with the fewest epileptogenic effects (6). More general, aliphatic phenothiazines (such as chlorpromazine) are thought to be more likely to cause seizures than the piperazine (such as fluphenazine and perphenazine) or piperidine (such as thioridazine) derivatives. Butyrophenones such as haloperidol are thought to carry a relatively low risk. Also, premarketing clinical trials of risperidone report a low incidence of seizure activity, 0.3 per cent (7). 1 Drugline nr 07882 (year 1991) 2 Drugline nr 04594 (year 1985) 3 Drugline nr 03597 (year 1983) 4 Whitworth AB, Fleischhacker WW: Adverse effects of antipsychotic drugs. Int Clin Psychopharmacol 1995; 9(Suppl 5): 21-27 5 Garcia PA, Alldredge BK: Drug-induced seizures. Neurol Clin 1994; 12: 85-99 6 Cold JA, Wells BG, Froemming JH: Seizure activity associated with antipsychotic therapy. DICP 1990; 24: 601-606 7 Franson KL, Hay DP, Neppe V, Dahdal WY, Mirza WU, Grossberg GT, Chatel DM, Szwabo PA, Kotegal S: Drug-induced seizures in the elderly. Causative agents and optimal management. Drugs Aging 1995; 7: 38-48