Double-Blind Placebo-Controlled Investigation of Naltrexone for Pathological Gambling

Pathological gambling (PG) is a significant public health problem that can cause significant devastation for the individuals affected and their families. Those afflicted may experience unemployment, considerable debt, marital problems, family dysfunction, legal troubles, incarceration, and mental health issues including suicidality. Prevalence estimates vary but most estimates put it at between 1% and 2%, with annual costs of over $5 billion in the United States alone. Thus, PG is costly not only for the affected individuals and their families, but also for society in general.

The current treatment as usual for PG is limited to various types of counseling, psychotherapy (e.g. cognitive behavioral therapy), and self-help groups such as Gamblers Anonymous. However, such treatment modalities have not been shown to be particularly effective. High rates or relapse are common and treatment attrition is often a concern.

Currently, no drugs are approved by the U.S. Food and Drug Administration for the treatment of PG. Pharmacological treatment studies are still in their infancy but show considerable promise. Several placebo-controlled, randomized clinical trials have been conducted, but results have been limited by small sample sizes, short durations, exclusion of individuals with co-occurring disorders, and heterogeneity in treatment response measures and diagnostic criteria used for inclusion.

Selective serotonin reuptake inhibitors (SSRIs) have shown mixed results in PG. Some studies have suggested a benefit of active drug over placebo while other studies have not. Mood stabilizers have not been extensively studied but some reports suggest that certain patients, such as those with co-morbid bipolar spectrum disorders, may benefit from this type of medication. Atypical antipsychotics have also been tried with limited success and may be more appropriate for patients with co-occurring psychotic disorders.

Opioid antagonists such as naltrexone and nalmefene, possibly through their modulation of the mesolimbic dopamine system, have demonstrated preliminary efficacy superior to placebo in treating PG. As with substance use disorders (SUD), it has been suggested that opioid antagonists may exert their therapeutic benefit by helping to reduce the appetitive urges or cravings present in symptomatology of addiction.