Elsevier

Biological Psychiatry

Volume 49, Issue 11, 1 June 2001, Pages 914-921
Biological Psychiatry

Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling

https://doi.org/10.1016/S0006-3223(01)01079-4Get rights and content

Abstract

Background: The authors’ goal was to assess the efficacy and tolerability of naltrexone in the treatment of pathologic gambling disorder.

Methods: Eighty-three subjects who met criteria for DSM-IV pathologic gambling disorder were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone or placebo trial. Naltrexone was started at 25 mg/day and titrated upward until maximum symptom improvement or 250 mg/day was achieved. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (PG-CGI-PT), clinician-rated CGI (PG-CGI-MD), and the Gambling Symptom Rating Scale (G-SAS). Side effects were monitored weekly and liver function tests biweekly.

Results: Data from 45 patients were analyzed. Using random regression analysis, significant improvement was noted in all three gambling symptom measures: patient-rated Clinical Global Impression, p < .001; clinician-rated CGI, p < .001; Gambling Symptom Rating Scale, p < .019. At study end, 75% of subjects taking naltrexone were much or very much improved on both the PE-CEI PT and the PG-CGI-MD, compared with only 24% of those on placebo. Elevated liver enzymes occurred in four subjects who were taking analgesics concurrently. Nausea was common during the first week of treatment.

Conclusions: Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.

Introduction

Pathologic gambling, a disorder characterized by persistent and recurrent maladaptive patterns of gambling behavior, seems to be relatively common. A recent metaanalysis shows not only the magnitude of the gambling problem but also its degree of penetration into various age groups (Shaffer et al 1999). The lifetime prevalence rates of pathologic gambling among adults, youth and college students have been reported as 1.6%, 3.9% and 4.7%, respectively. In addition, uncontrolled pathologic gambling often leads to bankruptcies, divorces, illegal acts, and psychiatric illnesses, including suicide (Phillips et al 1997).

Pathologic gambling disorder presents many challenges to effective treatment. The literature on pathologic gambling pharmacotherapy is expanding but is still relatively limited. Several classes of medications have been used with varying success to reduce the symptoms of pathologic gambling: serotonin reuptake inhibitors (SRIs) Hollander et al 1998, Hollander et al 2000, opioid antagonists (Crockford et al 1998) and mood stabilizers (Haller et al 1994). In addition, Gamblers Anonymous and pathologic gambling inpatient and outpatient treatment centers currently provide a major share of the treatment services for this group (Petry and Armentano 1999). Cognitive and behavior specialists are currently applying cognitive treatment principles in pathologic gambling disorder (Sylvain et al 1997).

Evidence of a possible serotonin dysfunction in pathologic gambling (DeCaria et al 1996) has led Hollander et al to conduct single-blind and double-blind studies using fluvoxamine in the treatment of pathologic gambling Hollander et al 1998, Hollander et al 2000. Similarly, Black et al (1997) demonstrated the efficacy of fluvoxamine in treating compulsive buying disorder, another obsessive-compulsive spectrum disorder.

Support for the use of naltrexone in the treatment of pathologic gambling comes from evidence of its effectiveness in the treatment of alcoholism, bulimia nervosa, drug abuse, borderline personality disorder with self-injurious behavior and other psychiatric disorders in which urges are the dominant symptom Brahen et al 1977, Herridge and Gold 1988, Jonas and Gold 1987, Keuler et al 1996, Marrazzi et al 1995a, Marrazzi et al 1995b, Martin et al 1973, Roth et al 1996, Sandyk 1987, Volpicelli et al 1992. To date, no systematic investigations of naltrexone in the treatment of pathologic gambling have been published.

Naltrexone inhibits dopamine neurons within the ventral tegmental area and diminishes dopamine function within the nucleus accumbens and its juxtaposed basal brain region Brahen et al 1977, Herridge and Gold 1988, Martin et al 1973. Dopamine function within these regions has been implicated in the subjective experience of pleasure and urges Berridge 1996, Kalivas and Barnes 1993, Keuler et al 1996, Sandyk 1987. One of the core symptoms of pathologic gambling is an uncontrolled urge triggered by a potential reward. We hypothesized that naltrexone would dampen the urges and pleasures associated with gambling but at a dose higher than 50 mg/day (Kim 1998).

Section snippets

Subjects

Subjects were recruited by newspaper advertisements. Eighty-nine subjects were screened. Eighty-three fulfilled the following inclusion and exclusion criteria and were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone versus placebo treatment. The study and the consent form were reviewed and approved by the Institutional Review Board.

Results

Thirty-eight of the 83 subjects enrolled were terminated before being treated with 100 mg/day of naltrexone for at least 2 weeks. Reasons for termination were: abnormal hepatic transaminase levels at baseline visit (n = 5), improvement of 50% or more on the G-SAS score during the first week placebo lead-in period (placebo responders) (n = 22), lost to follow-up before visit six (n = 6), became pregnant during the study (n = 1), developed intolerable side effects (naltrexone group) (n = 2),

Discussion

In our study, naltrexone treated patients showed a statistically significant improvement over the placebo group in all three main gambling symptom measures. At study end, 75% of subjects taking naltrexone were much or very much improved on both CGI-PT and CGI-MD, compared with only 24% of those on placebo. Although improvement was greater for the naltrexone group, the placebo group also improved significantly over time. In addition, approximately 25% of all subjects achieved substantial

Acknowledgements

Supported in part by a grant from the National Center for Responsible Gaming (NCRG). The authors acknowledge Joel Hektner, Ph.D., for statistical analysis and Rory Remmel, Ph.D., for the expert advice on naltrexone and analgesics interaction.

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