A Cochrane review [Abstract] 1 included 45 RCTs with 7760 participants. Four studies compared risperidone with amisulpride, 2 with aripiprazole, 11 with clozapine, 23 with olanzapine, 11 with quetiapine, two with sertindole, 3 with ziprasidone and none with zotepine. Attrition from the studies was high, 46.9%. Risperidone improved the general mental state (PANSS total score) slightly less than olanzapine (MD 1.94, CI 0.58 to 3.31; 15 RCTs, n = 2390), but slightly more than quetiapine (MD -3.09, CI -5.16 to -1.01; 9 RCTs, n = 1953) and ziprasidone (MD -3.91, CI -7.55 to -0.27; 3 RCTs, n = 1016). The comparisons with the other second-generation ("atypical") antipsychotics (SGA) were equivocal. Risperidone was less efficacious than olanzapine and clozapine in terms of leaving the studies early due to inefficacy, but more efficacious than ziprasidone in the same outcome.When measuring the overall acceptability of treatment by leaving the studies early, risperidone was slightly less acceptable than olanzapine and slightly more acceptable than ziprasidone.Risperidone produced somewhat more extrapyramidal side effects than a number of other SGAs (use of antiparkinson medication vs. clozapine: RR 2.57, CI 1.47 to 4.48, NNH 6, CI 33 to 3; 6 RCTs, n = 304, vs. olanzapine: RR 1.28, CI 1.06 to 1.55, NNH 17, CI 9 to 100; 13 RCTs, n = 2599, vs. quetiapine: RR 1.98, CI 1.16 to 3.39, NNH 20, CI 10 to 100; 6 RCTs, n = 1715, vs. ziprasidone: RR 1.42, CI 1.03 to 1.96, NNH not estimable; 2 RCTs, n = 822, parkinsonism vs. sertindole: RR 4.11, CI 1.44 to 11.73, NNH 14, CI 100 to 8; 1 RCT, n = 321). Risperidone also increased prolactin levels clearly more than all comparators with data available.Risperidone may also produce more weight gain and/or associated metabolic problems than amisulpride (weight gain: MD 0.99, CI 0.37 to 1.61; 3 RCTs, n = 585), aripiprazole (cholesterol increase: MD 22.30, CI 4.91 to 39.69; 1 RCT, n = 83) and ziprasidone (cholesterol increase: MD 8.58, CI 1.11 to 16.04; 2 RCTs, n = 767) but less than clozapine (weight gain: MD -3.30, CI -5.65 to -0.95; 3 RCTs n = 373), olanzapine (weight gain: MD -2.61, CI -3.74 to -1.48; 13 RCTs, n = 2116), quetiapine (cholesterol increase: MD -8.49, CI -12. 23 to -4.75; 5 RCTs, n = 1433) and sertindole (weight gain: MD -0.99, CI -1.86 to -0.12; 2 RCTs, n = 328). It may be less sedating than clozapine and quetiapine, lengthen the QTc interval less than sertindole (QTc change: MD -18.60, CI -22.37 to 14.83; 2 RCTs, n = 495), produce fewer seizures than clozapine (RR 0.22, CI 0.07 to 0.70, NNT 14 CI 8 to 33; 2 RCTs, n = 354) and less sexual dysfunction in men than sertindole (RR 0.34, CI 0.16 to 0.76, NNT 13 CI 8 to 33; 2 RCTs, n = 437).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, more than 20% loss to follow up, short follow-up time) and indirectness of evidence (differences in outcomes, very few data on patient-important outcomes).
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