Key words: Olanzapine; zisprasidone; schizophrenia; schizoaffective disorders; clinical trial; neurotherapeutics.

Introduction and Overview

Randomized, double-blind, head-to-head trials comparing the efficacy and safety of two atypical antipsychotics continue to be relatively uncommon, though they provide data which are the most readily generalizable to decision-making in clinical practice. Approximately 20 head-to-head trials have been published to date, with the majority reporting comparisons among three atypical drugs: clozapine, risperidone, and olanzapine (Cochrane group, 2005; Tuunainen et al., 2002). Few published comparator studies report data beyond 8 weeks of treatment. The results of available head-to-head trials have generally found minimal between-drug differences in efficacy. Instead, salient differences have been identified primarily in tolerability and safety outcomes.

The chronicity of schizophrenia and schizoaffective disorder, and the need for long-term therapy, make the safety and tolerability of antipsychotic drugs a central concern, both in terms of impact on compliance, and impact on longitudinal health outcomes. This is especially true since schizophrenia is associated with a 2–3-fold increase in all-cause mortality risk, with much of the 20% overall reduction in average life expectancy contributed by increased risk of cardiovascular (CV) and cerebrovascular mortality (Joukamaa et al., 2001; Harris & Barraclough, 1998). Schizophrenic patients appear to be a metabolically vulnerable population, with a significantly higher prevalence of CV risk factors such as obesity, diabetes, and dyslipidemia (Casey et al., 2004; Ryan et al., 2003; Davidson et al., 2001).