Another clinical study has sown doubts about the comparative efficacy of second-generation antipsychotic drugs, suggesting that newer, more expensive treatments such as Eli Lilly’s Zyprexa (olanzapine) and AstraZeneca’s Seroquel (quetiapine) are no more effective than the first-generation staple haloperidol.

Previous trials have raised the possibility that new may not be better in the drug treatment for schizophrenia. In late 2006, for example, an analysis of the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study funded by the US National Institutes of Health found that overall monthly costs were about 40%-50% higher for patients who received the second-generation antipsychotics Seroquel, Zyprexa, Geodon (ziprasidone, Pfizer) and Risperdal (risperidone, Johnson & Johnson) than for those given the first-generation perphenazine.

In terms of symptom relief and side-effect burden, though, there was no statistically significant difference between first and second-generation treatments, the researchers concluded.

In the latest study, published in The Lancet, an international team led by Professor René Kahn from the Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht in the Netherlands enrolled 498 patients for an open randomised controlled trial of haloperidol versus second-generation antipsychotics in first-episode schizophrenia. The trial was conducted at 50 sites in 14 countries.

The patients, who were 18-40 years old and met diagnostic criteria for schizophrenia, schizophreniform disorder or schizoaffective disorder, were assigned to either haloperidol 1-4mg per day (103 patients) or amisulpride (Solian, Sanofi-Aventis) 200-800mg/day (104 patients), olanzapine 5-20mg/day (105), quetiapine 200-750mg/day (104) or ziprasidone 40-160mg/day (82). The follow-up period was one year and the primary outcome of the trial was all-cause discontinuation of treatment.

The number of patients who came off treatment for any cause within 12 months was 63 for haloperidol, 32 for amisulpride, 30 for olanzapine, 51 for quetiapine and 31 for ziprasidone. However, symptom reductions were virtually the same across all five groups, at around 60%.

The outcomes showed that clinically meaningful treatment of first-episode schizophrenia with antipsychotics is achievable for at least one year, the authors commented. However, they added, “we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement”.

According to Kahn, the reason patients were more inclined to stay on the second-generation antipsychotics than on haloperidol was that doctors regarded the newer drugs as more effective.