A Randomized Double-Blind Trial of Atomoxetine for Cognitive Impairments in 32 People With Schizophrenia

Background: Currently available antipsychotic medications offer only modest, if any, effects on cognitive performance in people with schizophrenia. Treatments that would improve these impairments could lead to better functional outcomes. Atomoxetine is a nonstimulant, selective norepinephrine reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder. In animals, it has been shown to increase extracellular levels of acetylcholine and dopamine in cortical and hippocampal regions.

Method: Following a 2-week stabilization period, 32 subjects with DSM-IV-diagnosed schizophrenia or schizoaffective disorder were randomly assigned to atomoxetine (80 mg daily) or placebo for 8 weeks. All subjects were treated with antipsychotic monotherapy (excluding clozapine, aripiprazole, and first-generation antipsychotics). Neuropsychological test performance was the primary outcome variable, and the neuropsychological test battery included measures of attention, motor speed, executive function, processing speed, verbal and visual memory, and working memory (rated at baseline and end point). Symptom and side-effect ratings were performed every 2 weeks. The study was conducted from April 2004 through December 2006.

Results: There were no treatment group differences on the primary study outcome measure (overall mean z-score: Wilcoxon χ² = 0.21, df = 1, p =.64); nor was there significant evidence of variation in treatment effects on z-score changes across the individual neuropsychological tests (χ² = 8.22, df = 8, p =.41). No between-group differences were noted in symptom changes. Atomoxetine was well tolerated and was associated with a trend for improvement in extrapyramidal side effects relative to placebo (p=.063).

Conclusion: Our results provide further evidence that atomoxetine has limited benefit for improving cognition in people with schizophrenia.

Trial Registration: clinicaltrials.gov Identifier: NCT00161031