Rasagiline in the Treatment of the Persistent Negative Symptoms of Schizophrenia

Abstract

Objective: The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, for the treatment of persistent negative symptoms.

Methods: Sixty people with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori criteria for persistent negative symptoms, were randomized to receive rasagiline, 1mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess change in negative symptoms. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic learning task, and a delayed discounting task were used to assess cognition.

Results: In a mixed model analysis of covariance (MM-ANCOVA), with time as a continuous variable, there was a significant treatment × time effect for SANS total score (F = 5.61(df = 1,40.3), P = .023). The treatment × time interaction effect was also significant for the SANS avolition subscale score (F(1,40.2) = 10.41, P = .002). In a post hoc MM-ANCOVA analyses, with time as a categorical variable, group differences were significant at week 12 for SANS total score (t(37.3) = 2.15; P = .04; d = -0.41) and SANS avolition subscale score (t(49.0) = 3.06; P = .004; d = -0.46). There was a significant difference in number of participants with a ≥20% reduction in SANS avolition score (χ(2)(1) = 10.94; P = .0009), but not in SANS total score (χ(2)(1) = 1.11; P = .29). There were no significant group differences on the RBANS, N-Back, probabilistic learning, or delayed discounting tasks.

Conclusions: Study results support future studies of the utility of rasagiline for the treatment of negative symptoms, including avolition (clinicaltrials.gov trial number: NCT00492336).

Keywords: cognition; dopamine; monoamine oxidase; randomized clinical trial.