Galantamine for the Treatment of Cognitive Impairments in People With Schizophrenia

Department of Psychiatry, University of Maryland, Baltimore, MD, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 02/2008; 165(1):82-9. DOI: 10.1176/appi.ajp.2007.07050724
Source: PubMed


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.
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.
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.
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.

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Available from: Dwight Dickinson, Oct 09, 2015
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    • "As shown in an fMRI study, cholinergic action potentiates communication efficiency between cortical areas (Wylie et al., 2012). The use of these drugs in cholinergically healthy subjects might also be beneficial for enhancing cognitive function (Buchanan et al., 2008; Demeter and Sarter, 2013). "
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    ABSTRACT: The cholinergic system is a potent neuromodulatory system that plays critical roles in cortical plasticity, attention and learning. In this review, we propose that the cellular effects of acetylcholine (ACh) in the primary visual cortex during the processing of visual inputs might induce perceptual learning; i.e., long-term changes in visual perception. Specifically, the pairing of cholinergic activation with visual stimulation increases the signal-to-noise ratio, cue detection ability and long-term facilitation in the primary visual cortex. This cholinergic enhancement would increase the strength of thalamocortical afferents to facilitate the treatment of a novel stimulus while decreasing the cortico-cortical signaling to reduce recurrent or top-down modulation. This balance would be mediated by different cholinergic receptor subtypes that are located on both glutamatergic and GABAergic neurons of the different cortical layers. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation (LTP) and modulation of the excitatory/inhibitory balance. Recently, it was found that boosting the cholinergic system during visual training robustly enhances sensory perception in a long-term manner. Our hypothesis is that repetitive pairing of cholinergic and sensory stimulation over a long period of time induces long-term changes in the processing of trained stimuli that might improve perceptual ability. Various non-invasive approaches to the activation of the cholinergic neurons have strong potential to improve visual perception.
    Frontiers in Systems Neuroscience 09/2014; 8:172. DOI:10.3389/fnsys.2014.00172
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    • "Galantamine is a weak inhibitor of acetylcholinesterase and acts as an allosteric modulator of the nicotinic acetylcholine receptor (Santos et al., 2002). In both humans and animal models, galantamine is frequently used to treat memory impairments associated with Alzheimer 0 s disease and is being considered for use in schizophrenia (Alexander et al., 2012; Buchanan et al., 2008; Knopman and Morris, 1997; Wang et al., 2007). In addition, in the developmental NMDA receptor antagonist model, du Bois et al. (2009b) reported perinatal phencyclidine treatment alters the developmental expression of prefrontal and hippocampal muscarinic receptors. "
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    European journal of pharmacology 01/2014; 725(1). DOI:10.1016/j.ejphar.2014.01.007 · 2.53 Impact Factor
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    • "Adjunctive medication Pharmacological targets Study Effect size (95% CI) n % Dyer et al (2008) 17 Schubert et al (2006) 15 Akhondzadeh et al (2008) 44 Fagerlund et al (2007) 9 Friedman et al (2002) 10 Buchanan et al (2007) 21 Tsai et al (1998) 20 Goff et al (1999) 49 Goff et al (2001) 51 Tsai et al (1999) 22 Goff et al (2008) 50 Goff et al (2008) 52 Galantamine Galantamine Donepezil Donepezil Donepezil D-cycloerine D-serine D-cycloerine CX516 D-serine D-cycloerine CX516 AChEI AChEI AChEI AChEI AChEI Glutamate agonist Glutamate agonist Glutamate agonist Glutamate agonist Glutamate agonist Glutamate agonist Glutamate agonist 70.06 0.21 1.37 0.62 0.34 0.75 0.85 0.78 1.49 0.96 70.07 0.68 (70.94 to 0.82) (70.79 to 1.2) (0.56 to 2.11) (70.71 to 1.84) (70.52 to 1.18) (0.34 to 1.15) (0.06 to 1.59) (0.16 to 1.37) (0.36 to 2.48) (70.01 to 1.85) (70.48 to 0.34) (70.05 to 1.37) 20 16 30 11 26 104 29 46 18 20 92 33 4.5 3.6 6.7 2.5 5.8 23.4 6.5 10.3 4.0 4.5 20.7 7.4 < < < < < < < < < < < < 70.5 0 0.5 1.0 1.5 2.0 Fig. 1 "
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