Is there any difference between olanzapine (Zyprexa) and risperidone (Risperdal) regarding the effe

Fråga: Is there any difference between olanzapine (Zyprexa) and risperidone (Risperdal) regarding the effect on the seizure threshold?

The question concerns a 43-year-old man with epilepsy due to a brain tumor. He has now developed psychosis and needs treatment with a neuroleptic drug. The patient is also treated with carbamazepine (Tegretol).

Sammanfattning: Both risperidone and olanzapine may increase the risk of seizures in predisposed individuals. Available data do not support a difference in this respect between the two drugs. A typical neuroleptic may be a better choice. Monitoring of drug concentrations is advisable whenever carbamazepine is combined with a neuroleptic.

Svar: All antipsychotic and antidepressant drugs have a potential to cause seizures. According to a review article, larger investigations have shown incidence rates for the most commonly used antidepressants and neuroleptics of approximately 0.1 to 1.5 % in patients treated with therapeutic doses. Seizures triggered by psychotropic drugs seem to be a dose-dependent adverse effect. There are data indicating that psychotropic drugs cause epileptoform discharges almost exclusively in patients with pre-existing EEG abnormalities and/or history of epilepsy (1).

Olanzapine is an atypic antipsychotic drug similar in structure and pharmacology to clozapine. Olanzapine seems to have the same potential to cause EEG abnormalities, associated with a lowered seizure threshold and increased risk of epilepsy, as clozapine (1). There are also case reports describing EEG alterations and seizures in connection with olanzapine treatment (2,3,4).

Risperidone, another atypical antipsychotic, also has a potential to cause seizures (1). However, in a newly published study of carbamazepine-risperidone interactions, it is stated that risperidone often can be used successfully and safely in patients with epilepsy and with psychiatric comorbidity (6).

We found no studies that directly compare the frequency of seizures in connection with risperidone and olanzapine. In a study of EEG abnormalities in 323 hospitalised psychiatric patients, treated with various antipsychotic agents, 28 % (95 % CI 9.1-46.9) of patients treated with risperidone, and 38.5 % (95% CI 7.9-69.1) of olanzapine-treated patients had EEG abnormalities. The difference was not statistically significant (5). In the same study, typical neuroleptics, such as haloperidol, were accociated with a lower frequency of EEG abnormalities (14.5 %, CI 9.7-19.2), compared with the group of atypical drugs (31.6 %, CI 4.2-42.1) (p<0.001) (5).

The Swedish Adverse Drug Reaction Advisory Committee (SADRAC) has received one report of seizures and one report of status epilepticus from a total of 122 adverse drug reactions reported in connection with olanzapine treatment, compared with three cases of seizures reported for risperidone from a total of 240 adverse drug reactions (8). These data do not support any differences between the two drugs.

Risperidone is metabolised to 9-OH-risperidone by cytochrome P450 CYP2D6. The metabolite has the same receptor binding activity as the parent compound. Institution of risperidone to eight patients treated with carbamazepine increased the concentrations of carbamazepine significantly, indicating an inhibition of CYP3A4 (6). This result supports in vitro data, suggesting that risperidone in part may be metabolised also by CYP3A4. Carbamazepine may also decrease the concentrations of both risperidone (and its active metabolite) and olanzapine by enzyme induction (7). It is always advisable to monitor concentrations of both drugs when carbamazepine is used in combination with a neuroleptic.

In the present case, a typical neuroleptic, eg haloperidol, may be a better choice than either risperidone or olanzapine. Haloperidol may interact with carbamazepine in the same way as risperidone (7). In either case, monitoring of drug concentrations is advisable. 1 Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R. Effects of psychotropic drugs on seizure threshold. Drug Saf 2002;25(2):91-110. 2 Bonelli RM. Olanzapine-associated seizure. Ann Pharmacother 2003;37:149-50. 3 Woolley J, Smith S. Lowered seizure threshold on olanzapine. Br J Psychiatry 2001;178(1):85-6. 4 Pillmann F, Schlote K, Broich K, Marneros A. Electroencephalogram alterations during treatment with olanzapine. Psychopharmacol 2000;150:216-9. 5 Centorrino F, Price BH, Tuttle M, Bahk WM, Hennen J, Albert MJ, et al. EEG abnormalities during treatment with typical and atypical antipsychotics. Am J Psychiatry 2002;159:109-15. 6 Mula M, Monaco F. Carbamazepine-risperidone interactions in patients with epilepsy. Clin Neuropharmacol 2002;25(2):97-100. 7 FASS 2003 (The Swedish catalogue of approved medical products) 8 Swedis (The Swedish Drug Information System) (cited 2003-04-03)