Second-generation drugs, introduced over a decade ago, are purported to be more effective and less likely to induce motor side effects, such as stiffness and tremors, than first-generation drugs. However, results from studies comparing the 2 types of drugs have not been reliable -- studies have over-represented men and under-represented those with other issues such as drug abuse. Moreover, these trials were often too short. The question of which drugs are more effective is an important one, as many of the newer drugs are more expensive.

Rene Kahn, MD, PhD, University Medical Centre, Utrecht, Netherlands, and colleagues conducted an open, randomised trial in 14 countries (13 European countries and Israel), which included 498 patients aged 18 to 40 years. The participants were randomly assigned to 1 low-dose first-generation drug (haloperidol) (n = 103) or to 1 of 4 higher-dose second-generation drugs (amisulpride [n = 104], olanzapine [n = 105], quetiapine [n = 104], or ziprasidone [n = 82]).

Over the following 12 months, more patients discontinued treatment in the haloperidol group (63 individuals), than in the others: amisulpride (32), olanzapine (30), quetiapine (51), and ziprasidone (31). However, the reductions in all symptoms were about the same for all groups, at around 60% -- what the authors described as "a clinically meaningful response." When the authors further analysed the data according to gender, tendencies towards suicide, and substance abuse, they found no significant differences among the drugs.

The authors concluded, "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."

In an accompanying commentary, Robert A. Rosenheck, MD, Department of Veterans Affairs Connecticut Health Care System, Bedford, Massachusetts, said, "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."

SOURCE: The Lancet

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