Clinical Assessment and Management of Pathological Gambling

Pharmacological treatment
Several drugs have been investigated as treatments for PG, and the range of medication classes (opioid antagonists, SSRIs, mood stabilizers) reflects the heterogeneity of individuals who are pathological gamblers. Because no medication is currently FDA-approved to treat PG, patients should be informed of off-label use of medications for the disorder, as well as the empirical basis for considering pharmacological treatment (Table 2).

Opioid antagonists. The dopaminergic system, which influences the rewarding and reinforcing behaviors in substance use disorders, has also been implicated in PG. It has been proposed that alterations in dopaminergic pathways underlie the reward-seeking behaviors (eg, in gambling and drug use) that trigger the release of dopamine and produce feelings of pleasure.⁷ Opioid antagonists are thought to decrease dopamine neurotransmission in the nucleus accumbens, thereby affecting the motivational neurocircuitry and dampening gambling-related excitement and cravings.¹⁶

Initially, open-label treatment suggested the efficacy of high dosages of naltrexone (mean dosages of 157 mg/d)—an FDA-approved treatment for alcohol and opioid dependence—in reducing the intensity of gambling urges, thoughts, and behaviors.¹⁷ A 12-week double-blind placebo-controlled trial of naltrexone demonstrated superiority to placebo in 45 subjects who were pathological gamblers.¹⁸ The drug was effective in reducing the frequency and intensity of gambling urges and behaviors (mean dosage of 188 mg/d). Naltrexone's clinical use, however, is limited by its significant side effects and its tendency to elevate enzyme levels in the liver, especially in patients taking NSAIDs.¹⁹

A recently completed multicenter study demonstrated the efficacy of another opioid antagonist, nalmefene, in the treatment of PG. In a sample of 207 subjects, nalmefene dosages of 25 and 50 mg/d demonstrated statistically significant improvements (P = .007, P = .016, respectively) in gambling symptoms (reduced gambling urges, thoughts, and behaviors) compared with placebo in a 16-week double-blind trial.²⁰ Although nalmefene, like naltrexone, causes nausea in some individuals, it was not associated with hepatotoxicity in this large study.

Antidepressants. Pathological gamblers demonstrated diminished activation of the ventral medial prefrontal cortex (vmPFC) when they viewed gambling-related videotapes or during a simulated gambling task.^21,22 These findings suggest that decreased serotonin function within the vmPFC may engender disinhibition and contribute to PG. Thus, drugs targeting serotonin neurotransmission have been examined in PG treatment.

Data from double-blind randomized pharmacotherapy trials of SSRIs in the treatment of PG, although promising, have been inconclusive, with only some trials showing superior efficacy when compared with placebo (see Table 2).

Some important findings, however, emerge from these studies. First, antidepressants—particularly those that influence serotonergic systems, like the SSRIs—may be effective in reducing the symptoms of PG. Second, the effects of antidepressants appear to be independent of underlying depressive or anxiety symptoms.