Leo Sher, M.D.

Ten years ago, a seminal research report, “Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial” was published in a 2008 issue of The Lancet (1). A large international group of research collaborators led by Professor Rene S. Kahn compared the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol.

This controlled trial of haloperidol versus second-generation antipsychotic drugs was conducted in 50 sites, of which 36 were university hospitals, in 14 countries: Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Israel, Italy, Netherlands, Poland, Romania, Spain, Sweden, and Switzerland. 498 patients aged 18–40 years and who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were included in the study. Patients were excluded if more than 2 years had passed since the beginning of positive symptoms; if any antipsychotic medication had been used for more than 2 weeks in the previous year, or for 6 weeks at any time. Study participants were randomly assigned to daily doses of: haloperidol 1–4 mg, amisulpride 200–800 mg, olanzapine 5–20 mg, quetiapine 200–750 mg, or ziprasidone 40–160 mg.

This research study has shown that in patients with first-episode schizophrenia and schizophreniform disorder, treatment discontinuation after 12 months was significantly larger in patients given a low dose of haloperidol than in study participants assigned to treatment with second-generation antipsychotic medications. Researchers found that symptom reductions were virtually the same in all 5 groups, at around 60%. The authors concluded that “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 is haloperidol in the treatment of these patients.”

Reference

1. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, López-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rössler A, Grobbee DE; EUFEST study group.Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008;371(9618):1085-97. doi: 10.1016/S0140-6736(08)60486-9.