Have long-term hepatic side effects been reported for risperidone and which antipsychotic drug is t

Fråga: Have long-term hepatic side effects been reported for risperidone and which antipsychotic drug is the best alternative?

The question relates to a patient treated with Risperdal (risperidone) for more than one year. The current dose is 3 mg daily. There was a gradual increase in aminotransferase and gamma glutamyltransferase levels over the last months.

Laboratory values were: ALAT (alanine aminotransferase) 4.28 ukat/L; ASAT (aspartate aminotranferase) 1.88 ukat/L and GGT (gamma glutamyltranferase) 2.30 ukat/L respectively. The patient has no other known liver dysfunction or over consumption of alcohol.

Concomitant drugs: Mallorol (thioridazin) 10 mg in the evening.

Sammanfattning: Hepatic side effects with elevated aminotransferase, gammaglutamyltranferase and alkaline phosfatase values have been described as adverse effects of risperidone treatment in the literature and there is a sufficient number of case reports supporting this. The choice of antipsychotic drug will depend upon the patient´s earlier drug therapy and therefore no recommendation is made here.

Svar: The question concerning liver reaction, as an adverse effect of treatment with risperisdone, has previously been discussed in two Drugline documents (1,2). To summarise, the documentation consists of 5 cases of liver reactions judged as possibly related to risperidone by SADRAC, 3 case reports of elevated liver enzyme levels where in two patients the timing was considered to support a cause-effect connection and one cohort study including 38 youths were one patient developed a mild increase of ALAT not considered clinically important.

In the WHO adverse drug reaction database, Intdis, there are 294 reports of liver dysfunction with risperidone treatment. However, these reports are not evaluated due to the differences of the reporting system in the participating countries (3).

In an updated literature search concerning risperidone and liver toxicity one case study (4) and an additional 4 case reports (5,6) were found.

A prospective case study was carried out on 13 treated risperidone children (6-18 years) with a schizophrenia diagnosis (4). Two patients, treated for 17 and 7 months respectively, showed elevated aminotranferase levels, both with ALAT 3 times the upper limit when screened for hepatic side effects. The interpretation of these data is subject to controversy since several confounding factors such as concomitant treatment with drugs known to cause liver reactions exists (7).

Fuller et al describes two case reports of risperidone as the causative agent for liver reaction with elevated aminotranferase levels, with some uncertainty in the first case due to a history of alcohol abuse (5). In the first case report a 64-year-old male patient treated with risperidone 6 mg/d developed elevated amintranferase levels with 10 times the upper normal limit of ASAT and 7 times for ALAT. In the second case report a 68-year-old woman treated with risperidone 3mg twice daily developed similar symptoms with 3 times the upper normal limit of ASAT and 9 times for ALAT. In both patients liver function tests returned to normal after discontinuation of risperidone treatment.

There are two case reports in which treatment with risperidone led to transiently elevated liver enzyme levels (6). In both cases, one 22-year-old man and one 19-year-old male were treated with risperidone 6 mg/d and both developed elevated ALAT 106 U/L and ALAT 43 U/L and ASAT 112 U/L respectively. The aminotranferase levels declined spontaneously despite continuing risperidone treatment.

We recommend that this case be reported to SADRAC.