Galantamine for the treatment of cognitive impairments in people with schizophrenia.
OBJECTIVE
People with schizophrenia are characterized by a broad range of cognitive impairments. Despite appropriate treatment with conventional or second-generation antipsychotics, they continue to exhibit pronounced impairments. The current study was designed to examine the efficacy and safety of galantamine, an acetylcholinesterase inhibitor that also acts as an allosteric modulator at the alpha(4)beta(2) and alpha(7) nicotinic receptors, for the treatment of these impairments.


METHODS
Eighty-six people with schizophrenia were entered into a 12-week double-blind, placebo-controlled, randomized clinical trial. Forty-two subjects were assigned to galantamine and 44 were assigned to placebo. The efficacy of galantamine for cognitive impairments was evaluated with neuropsychological measures of attention, motor speed, processing speed, verbal and visual memory, and working memory.


RESULTS
The treatment effect for the overall composite score was not significant, but the heterogeneity of treatment effect analysis was significant. Follow-up analyses revealed that the subjects taking galantamine exhibited significant improvements on the WAIS-III digit symbol and verbal memory measures. In contrast, the subjects taking placebo showed a significant improvement on the GDS distractibility test. The group differences on the WAIS-III digit symbol and GDS distractibility test remained significant after correction for multiple comparisons. There were no significant between-group differences in motor speed or working memory. In general, safety analyses revealed that galantamine was well tolerated.


CONCLUSIONS
Study results suggest that galantamine may have selective benefits for aspects of processing speed and verbal memory but interferes with practice effects during the performance of an attention task.
Buchanan
Robert W
RW
Department of Psychiatry, University of Maryland, Baltimore, MD, USA. rwbuchanan@mprc.umaryland.edu
Conley
Robert R
RR
Dickinson
Dwight
D
Ball
M Patricia
MP
Feldman
Stephanie
S
Gold
James M
JM
McMahon
Robert P
RP
D001288:Attention / Q000187:drug effects; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005500:Follow-Up Studies; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011214:Practice, Psychological; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014888:Wechsler Scales / Q000706:statistics & numerical data; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine