An updated Cochrane review [Abstract] 1 included 55 trials (total n >10 000 people with schizophrenia). Olanzapine appeared superior to placebo at 6 weeks for the outcome of 'no important clinical response' (any dose, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27; 2 RCTs n=418). Attrition from the studies was >50% by 6 weeks. Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight.
For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (RR 0.90 CI 0.76 to 1.06; 4 RCTs, n=2 778), with fewer extrapyramidal adverse effects. There was high attrition in both groups (38% attrition by 6 weeks, RR 0.81 CI 0.65 to 1.02; 14 RCTs, n=3 344). Weight change data for the short term are not statistically significant but results between 3 to 12 months suggest a clinically important average gain of 4 kilograms for people given olanzapine (WMD 4.62, CI 0.6 to 8.64; 4 RCTs, n=186).
Olanzapine may cause fewer extrapyramidal adverse effects than other atypical drugs. Olanzapine produces more weight gain than other atypicals (gain at 2 years: RR 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7; 1 RCT, n=980). There are very few data for people with first episode illness (duration 6 weeks, 1 RCT, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). A total of 23% of people left by 8 weeks; 48% by 3 to 12 months (RR 0.91 CI 0.82 to 1.00; 11 RCTs, n=1 847).
A new Cochrane review [Abstract] 2 included 50 trials with 9 476 participants with schizophrenia or schizophrenia-like psychosis. The trials provided data for 6 comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). Half of the trials were short term studies (up to 12 weeks) and only 9 were long term studies (follow-up more than 26 weeks).The overall loss to follow up was high (49.2%).Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (WMD -4.96, CI -8.06 to -1.85; 2 RCTs, n=794), quetiapine (WMD -3.66, CI -5.39 to -1.93; 10 RCTs, n=1449), risperidone (WMD -1.94, CI -3.31 to -0.58; 15 RCTs, n=2 390) and ziprasidone (WMD -8.32 CI -10.99 to -5.64; 4 RCTs, n=1 291), but not more than amisulpride or clozapine. This was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (RR 0.56, CI 0.44 to 0.70, NNT 11 CI 6 to 50; 8 RCTs, n=1 563), risperidone (RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100; 14 RCTs, n=2 744) and ziprasidone (RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33; 5 RCTs, n=1 937).Except for clozapine, all comparators induced less weight gain than olanzapine. Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication: RR 2.05, CI 1.26 to 3.32, NNH 25 CI 14 to 100; 6 RCTs, n=1 090), but less than risperidone (use of antiparkinson medication: RR 0.78, CI 0.65 to 0.95, NNH 17 CI 9 to 100; 13 RCTs, n=2 599) and ziprasidone (use of antiparkinson medication: RR 0.70, CI 0.50 to 0.97, NNH not estimable; 4 RCTs, n=1 732). It may also increase prolactin level more than aripiprazole, clozapine and quetiapine, but clearly less than risperidone (WMD -22.84, CI -27.98 to -17.69; 6 RCTs, n=1 291).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, more than 20% loss to follow up) and indirectness (short follow-up). The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects.
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