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BioMed Research International
Volume 2014 (2014), Article ID 109786, 11 pages
Review Article

Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives

1Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy
2Department of Neuroscience and Imaging, “G. d’Annunzio” University, Chieti, Italy

Received 28 February 2014; Accepted 22 May 2014; Published 12 June 2014

Academic Editor: Sophia Achab

Copyright © 2014 Mauro Pettorruso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil) will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms) in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.