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Question: What is the relative efficacy of low dose haloperidol and second generation antipsychotic (SGA) drugs for first episode schizophrenia?Patients: 498 adults (aged 18-40 years) with a first episode of DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder (assessed using the Mini International Neuropsychiatric Interview plus).Main exclusions: positive symptoms starting over 2 years previously; use of antipsychotic drugs for more than 2 weeks in the preceding year, or for 6 weeks at any time; or known intolerance or contraindication to study drugs.Setting: 50 sites in 13 European countries and Israel; recruitment December 2002 to January 2006.Intervention: Low dose haloperidol (1-4 mg/day) or one of four SGAs: amisulpride (200-800 mg/day), olanzapine (5-20 mg/day), quetiapine (200-750 mg/day), or ziprasidone (40-160 mg/day). All drugs were given orally.Outcomes: Primary outcome: rate of treatment discontinuation for any cause (defined as use of a dose of study drug either higher or lower than the predefined range, complete discontinuation of study drug, use of another antipsychotic for more than 14 days in a 6-month period, use of any parenteral antipsychotic for more than 14 days in a 6-month period). Secondary outcomes: efficacy (including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI) Scale, Global Assessment of Functioning (GAF) scale; Calgary Depression Scale for Schizophrenia (CDSS), Manchester Short Assessment of Quality of Life Scale (MANSA), adherence to antipsychotic drugs); safety (including admission to hospital).Patient follow-up:69% completed follow-up (100% included in primary analyses).METHODSDesign: Randomised controlled trial.Allocation: Concealed.Blinding: Unblinded.Follow-up period: One year.MAIN RESULTSDuring the 12 month study, 63 patients taking haloperidol discontinued treatment (Kaplan-Meier estimate 72%), compared with 51 taking quetiapine (53%), 31 taking ziprasidone (45%), 32 taking amisulpride (40%) and 30 taking olanzapine (33%). The SGAs significantly reduced discontinuation (HR quetiapine 0.52, 95% CI 0.35 to 0.76; HR ziprasidone 0.51, 95% CI 0.32 to 0.81; HR amisulpride 0.37, 95% CI 0.24 to 0.57; HR olanzapine 0.28, 95% CI 0.18 to 0.43). Before discontinuation there was no difference between the groups in efficacy on the PANSS (p = 0.70), CDSS (p = 0.94), MANSA (p = 0.12) or in adherence to antipsychotics (p = 0.15). There were differences on the CGI (p = 0.0006) and GAF (p = 0.006), with a tendency for better scores with SGAs than haloperidol.CONCLUSIONSSecond generation antipsychotics reduce the rate of discontinuation over a 1-year period in people with first episode schizophrenia compared to haloperidol. [ABSTRACT FROM AUTHOR]