The Pharmaceutical Journal
Vol 275 No 7368 p363
24 September 2005

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New and old antipsychotics have similar efficacy

First and second generation antipsychotics are comparably effective but both associated with high rates of stopping therapy, according to research published in the New England Journal of Medicine this week (2005;353:1209).

Jeffrey Lieberman, department of psychiatry, Columbia University, New York, and colleagues conducted a randomised controlled trial involving 1,493 patients with schizophrenia. Patients received either the first generation antipsychotic perphenazine or a second generation antipsychotic — olanzapine, quetiapine or risperidone for up to 18 months. Ziprasidone was also included following its approval by the US Food and Drug Administration. The primary outcome measure was time to discontinuation of the drug for any reason. Patients’ symptoms were also evaluated.

Overall, 74 per cent of patients discontinued the study medication before 18 months. Discontinuation was highest among the quetiapine group (82 per cent) and lowest among the olanzapine group (64 per cent).

Olanzapine was considered the most effective drug in terms of rates of stopping therapy — time to discontinuation for any cause was longer in the olanzapine than the quetiapine (P<0.001) or risperidone group (P=0.002). Time to discontinuation due to side effects was similar in all groups, however olanzapine was associated with more stopping of therapy due to weight gain and increases in glycosylated haemoglobin, cholesterol and triglycerides. Results for the other second generation antipsychotics and perphenazine were similar in most respects, say the researchers.

An accompanying editorial (ibid, p1286) notes that clozapine was omitted because it has already been observed to have superior efficacy. “It would thus seem reasonable to try olanzapine and clozapine in any patient with schizophrenia who has not had a full clinical remission of the illness, which includes the reversal of cognitive and psychosocial disabilities. However, it is also prudent to switch treatment from these drugs to one of the others if a metabolic syndrome is threatening the patient’s general health,” it says.