A systematic review 1 including 150 studies with a total of 21 533 subjects was abstracted in DARE. All the studies were double-blinded. In patients with schizophrenia or related disorders second-generation antipsychotics (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) were compared with first-generation drugs (haloperidol, chlorpromazine, perphenazine, fluphenazine, flupenthixol, perazine, thioridazine, levomepromazine, chlopenthixol, zuclopenthixol, mosapramine, tiothixene, clocapramine, trifluoperazine, periciacine). Outcomes included overall efficacy, positive, negative and depressive symptoms, relapse, quality of life, extrapyramidial side-effects, weight gain and sedation. The majority of included studies had duration of maximum of 12 weeks. Pooled results showed that overall efficacy was greater in 4 second-generation drugs (amisulpride, clozapine, olanzapine, and risperidone) with standardised mean differences (SMD) ranging from -0.52 to -0.13, p<0.002. The NNT for one additional responder was between 6 (95% CI 4, 10) for amisulpride and 15 (95% CI 9, 36) for risperidone. These drugs were also more effective in terms of treating positive and negative symptoms (SMD range: -0.36, -0.13, p<0.005). Amisulpride, clozapine, olanzapine, aripiprazole and quetiapine were more efficacious that first-generation drugs in treating depression (SMD range: -0.51, -0.12, p<0.04). Relapse was improved in 4 studies (n=1008) of olanzapine, RR 0.67 (95% CI 0.49, 0.92; NNT 17), 5 studies (n=1,174) of risperidone, RR 0.74 (95% CI 0.63, 0.87; NNT 11) and one study (n=282) of sertindole, RR 0.17 (95% CI 0.04, 0.73; NNT 14) when compared with first-generation drugs. Quality of life was improved in 3 of 17 studies following treatment with amisulpride, clozapine, and sertindole (SMD range: -0.44, -0.24, p<0.039). There were reductions in extrapyramidal side effects in all second-generation drugs when compared to haloperidol (p<0.037; NNT varied between 2 for clozapine and 5 for zotepine). However, this was not the case for the majority of drugs when compared with low-potency first generation drugs. Amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole and zotepine were associated with weight gain when compared to haloperidol (mean weight gain difference range: 0.9 to 3.4, p<0.04). Increased sedation was reported with clozapine (NNH 5), quetiapine (NNH 13) and zotepine (NNH not significant) (RR range 1.50 to 2.07, p<0.047) and aripiprazole was less sedating RR 0.65 (95% CI 0.45, 0.95; p=0.024; no NNH reported). Only clozapine was more sedating than low-potency first generation drugs, p=0.003.
Comment: The quality of evidence is downgraded by indirectness (short follow-up time, differences in studied patients)
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