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Evidence summaries

New Generation Antipsychotics for First Episode Schizophrenia

New generation antipsychotics appear to produce fewer adverse effects than haloperidol in the short term, but there is insufficient comparative data on effectiveness and on long-term compliance. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 2 studies with a total of 266 patients. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol.

A systematic review 2 including 21 double-blind RCTs with a total of 7 245 subjects was abstracted in DARE. All new antipsychotics reduced the BPRS (Brief Psychiatric Rating Scale) global score more effectively than placebo. For global efficacy, risperidone and olanzapine produced significant but modest effects that were superior to haloperidol. For negative symptoms, olanzapine and risperidone were both superior to haloperidol whereas sertindole and haloperidol were equally effective. The new antipsychotics were associated with less antiparkinson medication use than haloperidol, but risperidone was not significantly better than zuclopenthixol or perphenazine, and quetiapine was not significantly better than chlorpromazine.

Comment: The quality of evidence is downgraded by sparse data. There is also uncertainty of equipotent dosing.

    References

    • Rummel C, Hamann J, Kissling W, Leucht S. New generation antipsychotics for first episode schizophrenia. Cochrane Database Syst Rev 2003;(4):CD004410. [PubMed]
    • Leucht S, Pitschel-Walz G, Abraham D, Kissling W. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 1999 Jan 4;35(1):51-68. [PubMed] [DARE]

Primary/Secondary Keywords