Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission: an open randomized clinical trial (EUFEST)

Background: Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales. We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics (SGAs) on ≥ 50% response and remission. Methods: In an open randomized clinical trial in 14 countries, 498 unselected first-episode patients with schizophrenia were assigned to haloperidol (1-4 mg/d; n = 103), amisulpride (200-800 mg/d; n = 104), olanzapine (5-20 mg/d; n = 105), quetiapine (200-750 mg/d; n = 104), or ziprasidone (40-160 mg/d; n = 82). Primary outcomes were ≥ 50% response and remission within 12 months, as measured with the Positive and Negative Syndrome Scale. Analysis was by intention-to-treat. Results: Within 12 months, the proportions of patients with ≥ 50% response were 37% for haloperidol, 67% for amisulpride, 67% for olanzapine, 46% for quetiapine, and 56% for ziprasidone. Comparisons with haloperidol showed a higher likelihood for ≥ 50% response with amisulpride (hazard ratio [HR] 2.27, [95% CI 1.51-3.42]), olanzapine (HR 2.07 [1.38-3.10]), and ziprasidone (HR 1.62 [1.02-2.56]). Within 12 months, the proportions of patients in remission were 17% for haloperidol, 40% for amisulpride, 41% for olanzapine, 24% for quetiapine, and 28% for ziprasidone. Comparisons with haloperidol showed a better chance for remission on amisulpride (HR 2.49, [95% CI 1.43-4.35]), olanzapine (HR 2.58 [1.48-4.48]), quetiapine (HR 1.96 [1.06-3.64]), and ziprasidone (HR 2.03 [1.07-3.87]). Conclusions: Substantial proportions of first-episode patients with schizophrenia showed clinically meaningful response and remission rates within 12 months. The proportions of response and remission were higher for most SGAs as compared to haloperidol.