Treatment of Pathological Gambling with Disulfiram: A Report of 2 Cases

Introduction

Pathological gambling (PG) is a condition consisting of persistent and repetitive patterns of gambling, often associated with impaired functioning, reduced quality of life, bankruptcy and divorce [1] [2]. The prevalence of PG in the general population is estimated as 0.42% in the U. S. [3], the corresponding rates in Germany range from 0.19 to 0.56% [4]. Although several lines of clinical evidence suggest common features of PG and substance dependence [5], the disorder is currently categorized in the group of “habit and impulse disorders” in ICD-10 [6] and “impulsive control disorders not elsewhere classified” in DSM-IV [7]. Shared characteristics of PG and substance dependence include genetic [8], phenomenological and clinical [9] as well as common neural features, especially alterations of the mesolimbic reward system [10]. An fMRI study reported a reduced activation in the ventral striatum and the ventromedial and ventrolateral prefrontal cortex in patients with PG in the processing of monetary rewards during a gambling paradigm in comparison to healthy subjects [11]. Similar results have been shown in patients with alcohol dependence [12] [13] [14] and cocaine dependence [15], suggesting a common pathophysiological mechanism in both PG and substance dependence and thereby substantiating the understanding of PG as a non-substance-related addiction.

Current treatment approaches for PG include cognitive-behavioral therapy as well as pharmacotherapies using opiate antagonists like naltrexone [16], lithium [17], selective serotonin reuptake inhibitors [18] and the glutamatergic agent N-acetylcysteine [19]. However, the overall effect sizes of these treatment concepts are only modest and approved pharmacotherapies are lacking.

Disulfiram, an aldehyde dehydrogenase inhibitor, is being used for more than 50 years as an aversion therapeutic agent for the treatment of alcohol dependence [20]. Besides this well-known mechanism of action, disulfiram is also able to inhibit the dopamine beta-hydroxylase which metabolizes dopamine to norepinephrine [21]. Via this effect, administration of disulfiram leads to an increase of dopamine concentrations while decreasing the concentrations of norepinephrine in the brain [22] [23]. Based upon the observations that PG is associated with diminished activation of the dopaminergic reward system [11] and elevated levels of norepinephrine or its metabolites in cerebrospinal fluid, plasma and urine [24], disulfiram has been hypothesized to be a new pharmacological treatment option for this disorder [25] [26]. In cocaine dependence, disulfiram has already shown preliminary efficacy in reducing relapse rates. However, there is only low evidence for its broad clinical use until now [27].

In this report, we present 2 cases of patients meeting the diagnostic criteria for PG according to ICD-10 and DSM-IV who received a pharmacotherapy with disulfiram. To assess changes in severity of PG, both patients completed the pathological gambling adaption of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS), a reliable and validated 10-item questionnaire [28], at every visit.

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