Topiramate on Gambling-Related Behaviours

The quest for an effective pharmacotherapy for problem gambling remains an important priority for the problem gambling treatment research field. While several medications have been evaluated in controlled clinical trials no medication has been shown to unequivocally reduce gambling behaviour and, to date, no medication has been approved for treating this disorder. Recently, topiramate, indicated for the treatment of seizure disorders, has shown some promise as a pharmacotherapy for problem gambling. The most persuasive evidence for the efficacy of topiramate has been reported for alcohol (in a placebo-controlled study) and for problem gambling (in which fluvoxamine served as an active control). No study has examined the efficacy of topiramate in a placebo-controlled clinical trial or examined its efficacy within specific sub-groups of gamblers.

Topiramate has recently been found to be effective in a number of psychiatric and addictive disorders. Dannon reported the first trial evaluating topiramate as a treatment for pathological gambling, comparing it to fluvoxamine. Treatment was delivered over a 12-week period with a maximum dose of 200 mg/d. Nine out of 15 topiramate subjects had achieved full remission of gambling behaviour compared to 6 out of 16 fluvoxamine subjects. However, both groups improved to a similar degree on other measures of psychopathology (e.g., anxiety). This study and Dannon's previous study of topiramate's efficacy in the treatment of kleptomania, suggests that topiramate may be particularly effective for Impulse-Control Disorders.

Topiramate-induced modulation of the noradrenergic pathways that mediate hyper- arousal, conditionability and intrusive/ emotional memories suggests that this medication may be particularly efficacious in problem gamblers characterized by hyper-arousal, anxiety and depression. Blaszczynski in their delineation of the Pathways Model of problem and pathological gambling, has identified a group of problem gamblers who self-regulate dysphoric emotional states through escape, dissociation and numbing (i.e., Emotionally Vulnerable problem gamblers). The Impulsivist and the Conditioned problem gambler, the two other sub-types described by Blaszczynski are characterized by conditions and histories that may be less effectively targeted by topiramate (i.e., impulsive, antisocial personality structure in the case of the Impulsive gamblers and irrational cognitions in the case of the Conditioned problem gambler). This population of gamblers, especially common among females, may report positive histories of substance abuse, anxiety and mood disorders, familial and childhood dysfunction, and familial gambling.

In an open-label study of topiramate with a sample of patients with post-traumatic stress disorder, an amelioration of dissociation and numbing was reported. These findings are also consistent with this medication's reported amnesic effects, and suggest that topiramate may reduce neural reactivity of problem gamblers that would otherwise increase the probability of engaging in gambling to self-regulate dysphoric emotional states.

The current study proposes to further evaluate the clinical efficacy of topiramate in a randomized, placebo-controlled clinical trial, the first study to do so. Interaction of the effects of the medication and gambling sub-type will be examined to determine whether the efficacy of topiramate is correlated with the specific biopsychosocial history of the gambler. An experimental trial of an acute dose of topiramate will run concurrently in order to identify cognitive-behavioural mechanisms that may mediate the clinical effects of topiramate on gambling-related behaviours evaluated in this study.