Research reported in The Lancet finds that when treating a first episode of schizophrenia, second-generation antipsychotic drugs are not necessarily better than the first-generation drug haloperidol.

Second-generation drugs were introduced over ten years ago. Compared to first-generation drugs, they were designed to be more effective and cause fewer motor side-effects such as stiffness and tremors. However, there is no conclusive evidence to show that this claim about second-generation drugs is true. Several previous studies have compared the two types of drugs, but their results are unreliable due to over-representation of men, under-representation of people with other issues like drug abuse, or trials that were too short. Because newer drugs are more expensive and doctors have to make the best treatment recommendations, a reliable comparison of the two drug types is necessary.

To compare the drugs, René Kahn (University Medical Centre, Utrecht, Netherlands) and colleagues selected 498 patients aged 18 to 40 years in 14 countries (13 European countries and Israel). The open randomized trial was structured such that the participants were randomly assigned to the low-dose first-generation drug (haloperidol), or one of four higher-dose second-generation drugs (amisulpride, olanzapine, quetiapine, or ziprasidone).

The researchers followed the participants over 12 months and found that patients in the haloperidol group were more likely to stop treatment than in the other groups. Specifically 63 individuals taking, haloperidol, 32 taking amisulpride, 30 taking olanzapine, 51 taking quetiapine, and 31 taking ziprasidone discontinued treatment. For all groups, the rate of reduction in all symptoms was about 60% – “a clinically meaningful response,” according to the authors. The findings did not change significantly when the authors controlled for sex, tendencies towards suicide, and substance abuse.

“Although the high continuation rates for several of the second-generation antipsychotic drugs suggest that clinically meaningful long-term antipsychotic treatment is achievable in the first episode of schizophrenia, it cannot be concluded that second-generation antipsychotic drugs are more efficacious than haloperidol in the treatment of these patients,” conclude the researchers.

An accompanying comment by Dr Robert A Rosenheck, (VA Connecticut Health Care System, USA) writes: “Whether use of atypical antipsychotics in either chronic or first-episode schizophrenia should be limited to situations in which they are specifically indicated (eg, in the presence of tardive dyskinesia, akathesia, or pseudoparkinsonism) is a question that must now be faced head-on. Addressing this question poses a major challenge to both cost-effectiveness assessment and to mental-health policy making.”

Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial
R S Kahn et al.
The Lancet 371(9618). March 28, 2008.

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Written by: Peter M Crosta