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

Table 1

Clinical trials and case series using glutamatergic drugs to treat pathological gambling.

Drug	Dosage; (mg/day)	Study design	Duration	Sample size	Methods	Cognitive outcome	Gambling outcome	Comments	References
Acamprosate	1,998	Open-label	8 + 2 weeks	26 PG pts	PG-YBOCS, G-SAS, CGI, gambling episodes	NA	77% of participants completed. Improvement on all efficacy scales. 65% were responders.	Improvement in ADHD Checklist scores.	Black et al., 2011 [6]
	999	Open-label	6 months	8 PG pts	Gambling relapse, VAS	NA	None reached 6-month abstinence. No change in VAS scores to relapse.		Dannon et al., 2011 [7]
Amantadine	150	Clinical case study	8 weeks	One PG patient	G-SAS, HDRS, YMRS	NA	Reduction of 43–64% in gambling symptoms severity (G-SAS).		Pettorruso et al., 2012 [8]
	200	Double-blind, placebo-controlled	17 weeks	17 PG pts with Parkinson’s disease	G-SAS, PG-YBOCS, SOGS	NA	Abolished daily PG in 7 pts. 5 pts reduced daily expenditures and time spent gambling.	Valuable option in Parkinson’s disease gambling behaviors	Thomas et al., 2010 [9]
Baclofen	30–50	Open-label	6 months	9 PG pts	Gambling relapse, VAS	NA	One patient reached 4-month abstinence. None reached 6-month abstinence. No change in VAS scores to relapse.		Dannon et al., 2011 [7]
Gabapentin, pregabalin	300–600	Case series	6 months	GB: 4 PG pts; PGB: 6 PG pts	G-SAS, VAS	NA		Reduction of gambling craving and withdrawal	Pettorruso et al., 2013 [10]
Memantine	10–30	Open-label	10 weeks	29 PG pts	PG-YBOCS, stop-signal task, IDED task	Reduced cognitive inflexibility	PG-YBOCS score and hours spent gambling decreased.	Target both gambling and cognitive deficits in PG	Grant et al., 2010 [11]
	20	Case report	8 weeks	One OCD, BD, PG pt	G-SAS		Reduction of more than 50% in GSAS scores.		Pavlovic, 2011 [12]
Modafinil	200	Double-blind, placebo-controlled	Single session	20 nontreatment-seeking PG pts	EIQ, IGT, cognitive tasks	In H-I pts reduced disinhibition and risky decision-making	In H-I pts decreased desire to gamble, salience, disinhibition, and risky decision-making. In L-I pts increased scores.	Impulsivity could moderate medication response in PG	Zack and Poulos, 2009 [13]
NAC	1,200–1,800	Open-label, double-blind discontinuation phase	8 + 6 weeks	27 PG pts	PG-YBOCS, G-SAS, CGI	NA	59.3% were respondents. Difference with placebo in discontinuation phase.	NAC targets craving in PG-addictive subtype	Grant et al., 2007 [14]
	1,200–3,000	RCT	12 weeks	28 PG, nicotine dependent, pts	SCI-PG, PG-YBOCS; Fagerström test for nicotine dependence	NA	During the 3-month followup, NAC was superior to placebo on PG severity.	NAC facilitates long-term behavioral therapy	Grant et al., 2014 [15]
Topiramate	200	Randomized, blind-rater vs fluvoxamine	12 weeks	15 PG pts (topiramate), 16 PG pts (fluvoxamine)	SOGS, PG-YBOCS, CGI	NA	9/12 pts reported full remission and 3/12 partial remission. Significant CGI improvement.		Dannon et al., 2005 [16]
	300	RCT	14 weeks	20 PG pts; 22 placebo	PG-YBOCS, G-SAS, CGI-I, BIS-11	Reduced impulsivity traits	No significant effect on the primary measures.	Small sample size. Study probably; underpowered	Berlin et al., 2013 [17]
	200	Clinical case study (add-on to lithium)	2 months	One pt with BD and PG comorbidities	None	NA	Gambling behavior abated after 2 months of combined treatment. On long-term followup the patient remained asymptomatic.	Valuable add-on treatment in BD-PG comorbidity	Nicolato et al., 2007 [18]

RCT: randomized-controlled trial; PG: pathological gambling; G-SAS: Gambling-Symptom Assessment Scale; PG-YBOCS: Yale-Brown Obsessive-Compulsive Scale modified for pathological gambling; HDRS: Hamilton Depression Rating Scale; YMRS: Young Mania Rating Scale; NA: not available; IDED task: intradimensional/extradimensional set shift task; SOSG: South Oaks Gambling Screen; EIQ: Eysenck Impulsiveness Questionnaire; IGT: Iowa gambling task; OCD: obsessive compulsive disorder; BD: bipolar disorder; H-I: high impulsivity; L-I: low impulsivity.