A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia.
Relationships between altered prefrontal cortical dopamine, norepinephrine, and some of the cognitive impairments of schizophrenia support an approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine reuptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we evaluated atomoxetine's cognitive effects in a pilot placebo-controlled trial in patients with schizophrenia. Moreover, a functional magnetic resonance imaging investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine. Twenty participants with schizophrenia were randomized to treatment with placebo or atomoxetine 80 mg daily for an 8-week parallel-designed treatment trial. Cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia. No significant cognitive improvement was associated with atomoxetine treatment. However, atomoxetine treatment was associated with significantly greater increases in working memory-related activation of the left dorsolateral prefrontal and left posterior cingulate cortices. The negative results of this study conflict with the effectiveness of amphetamine in enhancing the cognitive abilities of schizophrenic patients and may be related to the differential pattern of cortical activation and deactivation produced by amphetamine.
Friedman
Joseph I
JI
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. jfriedman1@rcn.com
Carpenter
David
D
Lu
Jing
J
Fan
Jin
J
Tang
Cheuk Y
CY
White
Leonard
L
Parrella
Michael
M
Bowler
Stephanie
S
Elbaz
Zeinab
Z
Flanagan
Lauren
L
Harvey
Philip D
PD
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D003072:Cognition Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D008279:Magnetic Resonance Imaging; D010865:Pilot Projects; D011437:Propylamines / Q000008:administration & dosage* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D018759:Adrenergic Uptake Inhibitors; D014150:Antipsychotic Agents; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride