Depot risperidone for schizophrenia

Abstract

Background: Risperidone is the first new generation antipsychotic drug made available in a long acting injection.

Objectives: To examine the clinical effects of depot risperidone for people with schizophrenia and schizophrenia-like psychoses.

Search strategy: We searched the Cochrane Schizophrenia Group's Register (December 2002), references of all included studies, and contacted industry and authors of included studies.

Selection criteria: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis: Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and quality assessed the results, and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD).

Main results: One study (n=400) compared depot risperidone with placebo but 56% of people did not complete the three-month study rendering most global and mental state data unusable. Risperidone depot compared with placebo did not affect levels of anxiety (n=400, RR 0.58 CI 0.32 to 1.05) but may decrease agitation (n=400, RR 0.60 CI 0.39 to 0.92). Risperidone depot did not substantially influence hallucinations (n=400, RR 1.23 CI 0.47 to 3.22) but 'psychosis' was reduced (n=400, RR 0.52 CI 0.33 to 0.83, NNT 9 CI 7 to 26). Attrition was higher for the placebo group compared with people allocated risperidone depot (n=400, RR 0.74 CI 0.63 to 0.88, NNT 6 CI 4 to 12). Severe adverse events were common (13% to 23%) but significantly more so in the placebo group (n=400, RR 0.59 CI 0.38 to 0.93, NNT 11 CI 7 to 70). Poor reporting, however, makes these difficult to interpret. Movement disorders were equally common in both groups (n=400, RR 2.38 CI 0.73 to 7.78) although it looks as if there is a trend for the higher depot doses to encourage movement disorders. One study (n=640) compared depot risperidone against oral risperidone for stable people with relatively mild illness. For global outcomes there was no clear difference between the depot group and oral group (n=640, RR 'no global improvement' 1.06 CI 0.92 to 1.22). Mental state measures were also similar across groups. Overall, in this study compliance was good (n=640, RR <4 injections or "major protocol violation" 1.16 CI 0.81 to 1.67). Adverse effects were poorly reported but over half of both groups reported some adverse effect (n=640, RR 1.04 CI 0.91 to 1.18).

Reviewer's conclusions: There is no reliable data to support the claim that depot risperidone is beneficial for people with schizophrenia. For reasonably well, stable people it may mean that the need for regular oral doses can be avoided, but adverse affects are not well reported. For more severely ill people, few benefits are evident although it may increase compliance with injections in comparison with placebo. Use of depot risperidone, especially at the higher doses, is weakly associated with movement disorders. Well designed and reported, randomised studies, firmly grounded in real world clinical practice are needed to fully assess the effects of this new preparation.