A 23-year-old schizophrenic man has been treated with clozapine for the last six months. Because of

Fråga: A 23-year-old schizophrenic man has been treated with clozapine for the last six months. Because of anxiety and mild EEG-changes he is also treated with clonazepam. The patient has heard about buspiron and is eager to try this new drug. Are there any known interactions between these three drugs?

Sammanfattning: We have found no evidence of interactions between clozapine, clonazepam or buspiron. The combination of buspiron and benzodiazepines is considered safe by the manufacturer. Drug monitoring of clonazepam and clozapine is recommended.

Svar: Clozapine is a neuroleptic drug, a dibenzodiazepine derivate, that have an effect on a wide range of transmittors.

Clonazepam is a benzodiazepine derivate with sedative and antiepileptic properties.

Buspirone is an anxiolytic agent with dopaminergic, noradrenergic and antiserotonergic actions. There are no pharmacodynamic interactions documented. Compared with benzodiazepines, buspiron has a slower onset of action (about two weeks) and lacks euphoriant activity, and patients who have been treated with benzodiazepins within one month, tend to have a poorer respons to buspiron (1). This is thought to be a lack of euphoric effect of buspiron rather than a pharmacological interaction.

All three substances are extensively metabolized, a circumstance that theoretically gives an opportunity for interaction. However, no evidence of this has been found in Medline or in pharmacological handbooks. The only interaction reported to buspiron is haloperidol, the level of which is increased 25-50 per cent due to inhibited metabolism. A previous Drugline answer concerning interactions between buspiron and amitriptyline, flupenthixol or oxazepam, gives no further information (2).

The manufacturer considers the combination of buspiron and benzodiazepines as safe, but cannot garantee the effectivness of such a combination. In cases of prominent benzodiazepine withdrawal symptoms, they suggest an overlapping period as a possibility, when switching to buspiron treatment (3,4).

However, as little information has been found on the subject, we recommend monitoring of concentration levels of clozapine and clonazepam before and after starting buspiron treatment.