Skip to main content
SpringerLink
Log in

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

  • original investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

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 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).

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. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CANTAB:

Cambridge Neuropsychological Test Automated Battery

CGI:

Clinical Global Impressions

G-SAS:

Gambling Symptom Assessment Scale

HAM-A:

Hamilton Anxiety Scale Rating

HAM-D:

Hamilton Depression Scale Rating

IDED:

Intra-dimensional/Extra-dimensional Set Shift task

NMDA:

N-methyl d-aspartate

PG:

Pathological Gambling

PG-YBOCS:

Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling

QoLI:

Quality of Life Inventory

SCID:

Structured Clinical Interview for DSM-IV

SDS:

Sheehan Disability Scale

SST:

Stop Signal Test

References

  • Aron AR, Robbins TW, Poldrack RA (2004) Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8:170–177

    Article  PubMed  Google Scholar 

  • Baker DA, McFarland K, Lake RW, Shen H, Toda S, Kalivas PW (2003) N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann NY Acad Sci 1003:349–351

    Article  PubMed  Google Scholar 

  • Bisaga A, Evans SM (2004) Acute effects of memantine in combination with alcohol in moderate drinkers. Psychopharmacol 172:16–24

    Article  CAS  Google Scholar 

  • Black DW (2004) An open-label trial of bupropion in the treatment of pathologic gambling. J Clin Psychopharmacol 24:108–110

    Article  PubMed  Google Scholar 

  • Black DW, Shaw MC, Allen J (2008) Extended release carbamazepine in the treatment of pathological gambling: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 32:1191–1194

    Article  CAS  PubMed  Google Scholar 

  • Blanco C, Petkova E, Ibáñez A, Sáiz-Ruiz J (2002) A pilot placebo-controlled study of fluvoxamine for pathological gambling. Ann Clin Psychiatry 14:9–15

    PubMed  Google Scholar 

  • Cambridge Cognition Limited (2006) CANTABeclipse, version 3. Cambridge Cognition Limited, Cambridge

    Google Scholar 

  • Cunningham-Williams RM, Cottler LB, Compton WM III, Spitznagel EL (1998) Taking chances: problem gamblers and mental health disorders—results from the St. Louis Epidemiologic Catchment Area study. Am J Publ Health 88:1093–1096

    Article  CAS  Google Scholar 

  • Evans SM, Levin FR, Brooks DJ, Garawi F (2007) A pilot double-blind treatment trial of memantine for alcohol dependence. Alcohol Clin Exp Res 31:775–782

    Article  CAS  PubMed  Google Scholar 

  • Farlow MR, Graham SM, Alva G (2008) Memantine for the treatment of Alzheimer’s disease: tolerability and safety data from clinical trials. Drug Saf 31(7):577–585

    Article  CAS  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV-patient edition (SCID-I/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York

    Google Scholar 

  • Frisch MB, Cornell J, Villaneuva M (1993) Clinical validation of the quality of life inventory: a measure of life satisfaction for use in treatment planning and outcome assessment. Psychol Assess 4:92–101

    Article  Google Scholar 

  • Grant JE, Kim SW (2005) Quality of life in kleptomania and pathological gambling. Compr Psychiatry 46:34–37

    Article  PubMed  Google Scholar 

  • Grant JE, Potenza MN (2006) Compulsive aspects of impulse control disorders. Psychiatr Clin North Am 29:539–551

    Article  PubMed  Google Scholar 

  • Grant JE, Steinberg MA, Kim SW, Rounsaville BJ, Potenza MN (2004) Preliminary validity and reliability testing of a structured clinical interview for pathological gambling (SCI-PG). Psychiatry Res 128:79–88

    Article  PubMed  Google Scholar 

  • Grant JE, Levine L, Kim D, Potenza MN (2005) Impulse control disorders in adult psychiatric inpatients. Am J Psychiatry 162:2184–2188

    Article  PubMed  Google Scholar 

  • Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, Kallio A (2006) A multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 163:303–312

    Article  PubMed  Google Scholar 

  • Grant JE, Kim SW, Odlaug BL (2007) N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry 62:652–657

    Article  CAS  PubMed  Google Scholar 

  • Grant JE, Kim SW, Hartman BK (2008) A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, for the treatment of pathological gambling urges. J Clin Psychiatry 69:783–789

    Article  CAS  PubMed  Google Scholar 

  • Grant JE, Donahue CJ, Odlaug BL, Kim SW, Miller MJ, Petry NM (2009) Imaginal desensitization plus motivational interviewing in the treatment of pathological gambling: a randomized controlled trial. Br J Psychiatry 195:266–267

    Article  PubMed  Google Scholar 

  • Grant JE, Schreiber L, Odlaug BL, Kim SW (2010) Pathologic gambling and bankruptcy. Compr Psychiatry 51:115–120

    Article  PubMed  Google Scholar 

  • Guy W (1976) ECDEU assessment manual for psychopharmacology. US Dept Health, Education and Welfare publication (ADM) 76–338. National Institute of Mental Health, Rockville, pp 218–222

    Google Scholar 

  • Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55

    CAS  PubMed  Google Scholar 

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  CAS  PubMed  Google Scholar 

  • Hampshire A, Owen AM (2006) Fractionating attentional control using event-related fMRI. Cereb Cortex 16(12):1679–1689

    Article  PubMed  Google Scholar 

  • Hampshire A, Chamberlain SR, Monti MM, Duncan J, Owen AM (2010) The role of the right inferior frontal gyrus: inhibition and attentional control. Neuroimage 50(3):1313–1319

    Article  PubMed  Google Scholar 

  • Hollander E, Pallanti S, Allen A, Sood E, Baldini Rossi N (2005) Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry 162:137–145

    Article  PubMed  Google Scholar 

  • Kim SW, Grant JE, Adson DE, Shin YC (2001) Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 49:914–921

    Article  CAS  PubMed  Google Scholar 

  • Kim SW, Grant JE, Potenza MN, Blanco C, Hollander E (2009) The Gambling Symptom Assessment Scale (G-SAS): a reliability and validity study. Psychiatry Res 166:76–84

    Article  PubMed  Google Scholar 

  • Krystal JH, Petrakis IL, Krupitsky E, Schutz C, Trevisan L, D'Souza DC (2003) NMDA receptor antagonism and the ethanol intoxication signal: from alcoholism risk to pharmacotherapy. Ann NY Acad Sci 1003:176–184

    Article  CAS  PubMed  Google Scholar 

  • Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS (2004) Neuropsychological assessment. Oxford University Press, New York

    Google Scholar 

  • Logan GD, Cowan WB, Davis KA (1984) On the ability to inhibit simple and choice reaction time responses: a model and a method. J Exp Psychol Hum Percept Perform 10:276–291

    Article  CAS  PubMed  Google Scholar 

  • Ma YY, Cepeda C, Cui CL (2009) The role of NMDA receptors in drug addiction. Int Rev Neurobiol 89:131–146

    Article  CAS  PubMed  Google Scholar 

  • Meisner F, Scheller C, Kneitz S, Sopper S, Neuen-Jacob E, Riederer P, Meulen V, Koutsilieri E (2008) Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine. Neuropsychopharmacol 33:2228–2236

    Article  CAS  Google Scholar 

  • Minkeviciene R, Banerjee P, Tanila H (2008) Cognition-enhancing and anxiolytic effects of memantine. Neuropharmacol 54:1079–1085

    Article  CAS  Google Scholar 

  • Owen AM, Roberts AC, Polkey CE, Sahakian BJ, Robbins TW (1991) Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 29(10):993–1006

    Article  CAS  PubMed  Google Scholar 

  • Pallanti S, DeCaria CM, Grant JE, Urpe M, Hollander E (2005) Reliability and validity of the pathological gambling adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS). J Gambl Stud 21:431–443

    Article  PubMed  Google Scholar 

  • Petry NM (2005) Pathological gambling: etiology, comorbidity, and treatment. American Psychological Association, Washington

    Book  Google Scholar 

  • Petry NM, Ammerman Y, Bohl J, Doersch A, Gay H, Kadden R, Molina C, Steinberg K (2006) Cognitive–behavioral therapy for pathological gamblers. J Consult Clin Psychol 74:555–567

    Article  PubMed  Google Scholar 

  • Potenza MN, Fiellin DA, Heninger GR, Rounsaville BJ, Mazure CM (2002) Gambling: an addictive behavior with health and primary care implications. J Gen Intern Med 17:721–732

    Article  PubMed  Google Scholar 

  • Repantis D, Laisney O, Heuser I (2010) Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 61(6):473–481

    Article  CAS  PubMed  Google Scholar 

  • Shaffer HJ, Hall MN, Vander Bilt J (1999) Estimating the prevalence of disordered gambling behavior in the United States and Canada: a research synthesis. Am J Publ Health 89:1369–1376

    Article  CAS  Google Scholar 

  • Sheehan DV (1983) The anxiety disease. Scribner's, New York

    Google Scholar 

  • Tait DS, Marston HM, Shahid M, Brown VJ (2009) Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions. Psychopharmacol (Berl) 202:295–306

    Article  CAS  Google Scholar 

  • Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I (2004) Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317–324

    Article  CAS  PubMed  Google Scholar 

  • Van Wageningen H, Jorgensen HA, Specht K, Hugdahl K (2010) A 1H-MR spectroscopy study of changes in glutamate and glutamine (Glx) concentrations in frontal spectra after administration of memantine. Cereb Cortex 20:798–803

    Article  PubMed  Google Scholar 

Download references

Funding/disclosures/conflicts of interest

This study was funded by a research grant from Forest Pharmaceuticals.

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 GlaxoSmithKline. 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.

Dr. Chamberlain has consulted for Cambridge Cognition, P1Vital, and Shire Pharmaceuticals.

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.

Dr. Kim and Mr. Odlaug have no financial disclosures to report.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Minnesota School of Medicine, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA

    Jon E. Grant, Brian L. Odlaug & Suck Won Kim

  2. Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

    Samuel R. Chamberlain

  3. Department of Psychiatry, Yale University, New Haven, CT, USA

    Marc N. Potenza

Authors
  1. Jon E. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel R. Chamberlain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian L. Odlaug
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marc N. Potenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suck Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jon E. Grant.

Additional information

Jon E. Grant and Samuel R. Chamberlain are joint first authors.

This study was registered on Clinicaltrials.gov with identifier NCT00585169 associated with it (URL: http://www.clinicaltrials.gov/ct2/show/NCT00585169?term = NCT00585169&rank = 1).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grant, J.E., Chamberlain, S.R., Odlaug, B.L. et al. Memantine shows promise in reducing gambling severity and cognitive inflexibility in pathological gambling: a pilot study. Psychopharmacology 212, 603–612 (2010). https://doi.org/10.1007/s00213-010-1994-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-010-1994-5

Keywords

Search

Navigation