Background: Schizophrenia is a chronic disease of global importance. The second-generation antipsychotic quetiapine has a favorable side-effect profile, however, its clinical effectiveness has been called into question when compared with first-generation antipsychotics such as haloperidol. This study evaluates the efficacy and tolerability of quetiapine versus haloperidol for first-episode schizophrenia in the outpatient setting.

Methods: 156 adult patients with first-episode schizophrenia participated in an outpatient clinical trial and were randomized to quetiapine (200 mg/d; n = 78) or haloperidol (5 mg/d; n = 78). The study medications were titrated to a mean daily dose of 705 mg for quetiapeine and 14 mg for haloperidol. The patients were assessed at baseline, six weeks, and twelve weeks. The primary outcome measures were positive and negative scores of the Positive and Negative Syndrome Scale (PANSS). Secondary measures were Global Assessment of Functioning (GAF) scale for overall psychosocial functioning, and Simpson-Angus Scale (SAS) for extra-pyramidal symptoms.

Results: At twelve weeks, the quetiapine group had a greater decrease in PANSS positive (18.9 vs. 15.3, p = 0.013) and negative scores (15.5 vs. 11.6, p = 0.012), however, haloperidol showed a greater decrease in general psychopathology score (23.8 vs. 27.7, p = 0.012). No significant difference between groups were found for total PANSS (58.3 vs. 54.8, p = 0.24) and GAF (45.7 vs. 46.2, p = 0.79).ANOVA identified significant group interactions on PANSS positive (F = 18.72, df = 1.6,52.4, p < 0.0001), negative (F = 5.20, df = 1.1,35.7, p < 0.0001), depression/anxiety (F = 106.49, df = 1.14,37.8, p < 0.0001), and total scores (F = 7.51, df = 1.4,45.6, p = 0.001).SAS (8.62 vs. 0.26, p < 0.0001) and adverse events of akathisia (78% vs. 0%, p = 0.000), parkinsonism (66.6% vs. 0%, p < 0.0001), and fatigue (84.6% vs. 66.6%, p = 0.009) were greater in haloperidol compared to quetiapine, whereas headache was more common in quetiapine treated patients (11.5% vs. 35.9%, p < 0.0001).

Conclusions: Quetiapine has greater efficacy for positive and negative symptoms with less extra-pyramidal symptoms than haloperidol when used for first-episode schizophrenia in the outpatient setting.

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