original investigation


, Volume 212, Issue 4, pp 603-612

First online:

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

  • Jon E. GrantAffiliated withDepartment of Psychiatry, University of Minnesota School of Medicine Email author 
  • , Samuel R. ChamberlainAffiliated withDepartment of Psychiatry, University of Cambridge, Addenbrooke’s Hospital
  • , Brian L. OdlaugAffiliated withDepartment of Psychiatry, University of Minnesota School of Medicine
  • , Marc N. PotenzaAffiliated withDepartment of Psychiatry, Yale University
  • , Suck Won KimAffiliated withDepartment of Psychiatry, University of Minnesota School of Medicine

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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.


This study sought to examine the safety and efficacy of Memantine in PG.


Twenty-nine subjects (18 females) with DSM-IV PG 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).


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.


These findings suggest that pharmacological manipulation of the glutamate system may target both gambling and cognitive deficits in PG. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.


Cognition Glutamate Impulsivity Treatment Pharmacology Addiction