title: Targeting the glutamatergic system to treat pathological gambling: current evidence and future perspectives.
abstract: 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.
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Mauro
authors.identifier: 0000-0002-4164-3040
authors.initials: M
authors.lastname: Pettorruso
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Risio
authors.affiliation: Department of Neuroscience and Imaging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Filippo
authors.identifier: 0000-0003-0290-3898
authors.initials: F
authors.lastname: Ruggeri
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Conte
authors.affiliation: Department of Neuroscience and Imaging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
authors.affiliation: Institute of Psychiatry and Psychology, Catholic University of the Sacred Heart, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Janiri
mesh_terms: D016739:Behavior, Addictive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D018683:Excitatory Amino Acid Agents / Q000627:therapeutic use*; D005715:Gambling / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D016202:N-Methylaspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018683:Excitatory Amino Acid Agents; D018698:Glutamic Acid; D016202:N-Methylaspartate; D004298:Dopamine