Management of depressive symptoms in schizophrenia

Abstract

Background: Although depressive symptoms are a frequently occurring phenomenon in schizophrenia, effective treatments remain an area of clinical need.

Objective: To assess the benefit of short-term treatment with the atypical antipsychotic asenapine versus placebo on depressive symptoms in patients with acute schizophrenia in an exacerbated state.

Methods: Data were pooled from intent-to-treat (ITT) populations of three 6-week, randomized controlled studies with fixed doses of asenapine (ASE; n=427), olanzapine (OLA; n=82), risperidone (RIS; n=54), haloperidol (HAL; n=97), or placebo (PLA; n=254). Change from baseline Calgary Depression Scale for Schizophrenia (CDSS) total score and individual item scores were assessed at Day 21 and Day 42 in the total patient population (n=914), and in patients presenting with a CDSS total score of .6 at baseline (n=248). Mixed model repeated measures (MMRM) analyses were performed on patient data.

Results: The observed change from baseline in CDSS total score was significantly larger with ASE.compared to PLA.at both Day 21 (p<0.05) and Day 42 (p<0.01) for the total patient population group, and at Day 21 (p<0.05) in patients with baseline CDSS total score .6. For both populations, there was a significant change from baseline in the CDSS depression item score with ASE.compared to PLA.at Day 21 (p<0.01, all patient population; p<0.05, patients with baseline CDSS .6), and at Day 42 (p<0.01) in the all patient population. Statistically significant changes from baseline, in favor of ASE versus PLA, were also observed in other individual CDSS item scores including hopelessness (p<0.05, Day 21, patients with baseline CDSS .6), self-depreciation (p<0.05, Day 42, all patient population), guilty ideas of reference (p<0.01, Day 42, all patient population), pathological guilt (p<0.01, Day 21, all patient population; p<0.05, Day 21 and Day 42, patients with baseline CDSS score .6), and observed depression (p<0.05, Day 21, all patient population).

Conclusions: ASE significantly improved a range of depressive symptoms in people with an acute exacerbation of schizophrenia, as measured by the CDSS. ASE may represent a beneficial treatment option for the management of depressive symptoms in patients with schizophrenia.

Trial registration: ClinicalTrials.gov NCT00156104 NCT00156117.

Keywords: Antipsychotic; Asenapine; Depression; Schizophrenia.