Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: A pilot study

Jon E. Grant; Samuel R. Chamberlain; Brian L. Odlaug; Marc N. Potenza; Suck Won Kim

doi:10.1007/s00213-010-1994-5

Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: A pilot study

Jon E. Grant, Samuel R. Chamberlain, Brian L. Odlaug, Marc N. Potenza, Suck Won Kim

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV G were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra- dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebocontrolled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

Original language	English (US)
Pages (from-to)	603-612
Number of pages	10
Journal	Psychopharmacology
Volume	212
Issue number	4
DOIs	https://doi.org/10.1007/s00213-010-1994-5
State	Published - Dec 2010

Bibliographical note

Funding Information:
Dr. Grant has received research grants from NIMH, NIDA, and National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, Forest Pharmaceuticals and Glax-oSmithKline. Dr. Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies. Dr. Grant has performed grant reviews for NIH and the Ontario Gambling Association. Dr. Grant has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. Dr. Grant has received honorarium from Indiana University Medical School, University of South Florida, the Mayo Medical School, the California Society of Addiction Medicine, the State of Arizona, the State of Massachusetts, the State of Oregon, the Province of Nova Scotia, and the Province of Alberta. Dr. Grant has received compensation as a consultant for law offices on issues related to impulse control disorders.

Funding Information:
Dr. Potenza has consulted for and advised Boehringer Ingelheim; has received research support from the National Institutes of Health, Veteran’s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices on issues related to addictions or impulse control disorders; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts.

Funding Information:
Funding/disclosures/conflicts of interest This study was funded by a research grant from Forest Pharmaceuticals.

Keywords

Addiction
Cognition
Glutamate
Impulsivity
Pharmacology
Treatment

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title = "Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: A pilot study",

abstract = "Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV G were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra- dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebocontrolled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.",

keywords = "Addiction, Cognition, Glutamate, Impulsivity, Pharmacology, Treatment",

author = "Grant, {Jon E.} and Chamberlain, {Samuel R.} and Odlaug, {Brian L.} and Potenza, {Marc N.} and Kim, {Suck Won}",

note = "Funding Information: Dr. Grant has received research grants from NIMH, NIDA, and National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, Forest Pharmaceuticals and Glax-oSmithKline. Dr. Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies. Dr. Grant has performed grant reviews for NIH and the Ontario Gambling Association. Dr. Grant has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. Dr. Grant has received honorarium from Indiana University Medical School, University of South Florida, the Mayo Medical School, the California Society of Addiction Medicine, the State of Arizona, the State of Massachusetts, the State of Oregon, the Province of Nova Scotia, and the Province of Alberta. Dr. Grant has received compensation as a consultant for law offices on issues related to impulse control disorders. Funding Information: Dr. Potenza has consulted for and advised Boehringer Ingelheim; has received research support from the National Institutes of Health, Veteran{\textquoteright}s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices on issues related to addictions or impulse control disorders; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. Funding Information: Funding/disclosures/conflicts of interest This study was funded by a research grant from Forest Pharmaceuticals.",

year = "2010",

month = dec,

doi = "10.1007/s00213-010-1994-5",

language = "English (US)",

volume = "212",

pages = "603--612",

journal = "Psychopharmacology",

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TY - JOUR

T1 - Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling

T2 - A pilot study

AU - Grant, Jon E.

AU - Chamberlain, Samuel R.

AU - Odlaug, Brian L.

AU - Potenza, Marc N.

AU - Kim, Suck Won

N1 - Funding Information: Dr. Grant has received research grants from NIMH, NIDA, and National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, Forest Pharmaceuticals and Glax-oSmithKline. Dr. Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies. Dr. Grant has performed grant reviews for NIH and the Ontario Gambling Association. Dr. Grant has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. Dr. Grant has received honorarium from Indiana University Medical School, University of South Florida, the Mayo Medical School, the California Society of Addiction Medicine, the State of Arizona, the State of Massachusetts, the State of Oregon, the Province of Nova Scotia, and the Province of Alberta. Dr. Grant has received compensation as a consultant for law offices on issues related to impulse control disorders. Funding Information: Dr. Potenza has consulted for and advised Boehringer Ingelheim; has received research support from the National Institutes of Health, Veteran’s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices on issues related to addictions or impulse control disorders; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. Funding Information: Funding/disclosures/conflicts of interest This study was funded by a research grant from Forest Pharmaceuticals.

PY - 2010/12

Y1 - 2010/12

N2 - Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV G were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra- dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebocontrolled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

AB - Rationale Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. Memantine, an N-methyl D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive decision making, suggesting it may help individuals with PG. Objective This study sought to examine the safety and efficacy of Memantine in PG. Methods Twenty-nine subjects (18 females) with DSM-IV G were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/day). Subjects were enrolled from January 2009 until April 2010. Change from baseline to study endpoint on the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Subjects underwent pre- and post-treatment cognitive assessments using the stop-signal task (assessing response impulsivity) and the intra-dimensional/extra- dimensional (ID/ED) set shift task (assessing cognitive flexibility). Results Twenty-eight of the 29 subjects (96.6%) completed the 10-week study. PG-YBOCS scores decreased from a mean of 21.8±4.3 at baseline to 8.9±7.1 at study endpoint (p<0.001). Hours spent gambling per week and money spent gambling both decreased significantly (p<0.001). Subjects also demonstrated a significant improvement in ID/ED total errors (p=0.037) at study endpoint. The mean effective dose of memantine was 23.4±8.1 mg/day. The medication was well-tolerated. Memantine treatment was associated with diminished gambling and improved cognitive flexibility. Conclusions These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebocontrolled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

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KW - Cognition

KW - Glutamate

KW - Impulsivity

KW - Pharmacology

KW - Treatment

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Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: A pilot study

Abstract

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Keywords

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