Thoughtsnin

A Sudden Case of Compulsive Gambling A 74-year-old man is brought to the office by concerned family members. Recently he has begun spending all day at the casino nearby and has lost much of his.

Abstract

Pathological gambling has received little attention from clinicians and researchers despite prevalence rates similar to or greater than those of schizophrenia and bipolar disorder. This article summarizes the phenomenology and associated psychopathology of this public health problem and presents results of studies of 3 types of pharmacological agents used to treat this disorder: serotonin reuptake inhibitors, opioid antagonists, and mood stabilizers.

Pathological gambling is characterized by persistent and recurrent gambling and is associated with impaired functioning, reduced quality of life, and high rates of bankruptcy, divorce, and criminal activity. The problem usually begins during adolescence or early adulthood, with males tending to start at an earlier age.^, Although gambling among women has become a significant problem with the proliferation of lottery tickets, casinos, and Internet gambling sites and the gradual acceptance of gambling as a legitimate form of entertainment, epidemiological studies still suggest that men represent the majority of pathological gamblers and that being male appears to be a risk factor for developing a gambling addiction during adolescence.^, Although there have been few prospective studies on the subject, there is a high incidence of pathological gambling among adolescents and young adults and a lower incidence among older adults; in addition, periods of abstinence and relapse are common among all pathological gamblers.

Diagnosing Pathological Gambling

Studies have shown that pathological gambling usually goes unrecognized in clinical settings mainly because clinicians fail to screen for the behavior. However, diagnosing the problem is usually straightforward and can be done by asking patients if they feel they cannot control their gambling or if they are preoccupied with gambling. An affirmative answer can be followed up with questions determining the degree of impairment (whether it’s affecting patients’ social or family life, their financial well-being, or their work) and the distress that this behavior causes. It must also be determined that a patient’s gambling behavior is not simply a symptom of bipolar disorder. Simple self-reporting and clinician-administered screening and diagnostic measures for pathological gambling and bipolar disorder are available.⁷

Relationship to Other Mental Illnesses

Although pathological gambling is classified as an impulse-control disorder, it has many similarities to substance abuse. Clinical similarities are reflected in the diagnostic criteria for both disorders and include symptoms of tolerance and withdrawal; repeated, unsuccessful attempts to cut back or stop; and impairment in major areas of life functioning. Epidemiological data also support a relationship between pathological gambling and substance abuse, as pathological gamblers are also likely to abuse alcohol and other drugs. Phenomenological data further support a relationship between behavioral and drug addictions. For example, high rates of pathological gambling and substance abuse have been reported during adolescence and young adulthood. In addition, the telescoping phenomenon, which reflects the rapid rate of progression from initial to problematic behavior in women compared with men, initially described for alcoholism has been applied to pathological gambling. Emerging biological data, such as those identifying genetic contributions to alcohol use and gambling disorders and changes in brain activity underlying gambling urges and cocaine cravings, provide further support for a relationship between pathological gambling and substance abuse.^,

Although much data support a close relationship between pathological gambling and substance abuse, pathological gambling also has been categorized as an obsessive-compulsive spectrum disorder as well as an affective spectrum disorder. The inclusion of pathological gambling within the obsessive-compulsive spectrum is based on the fact that people who are compulsive gamblers tend to have repetitive thoughts and behaviors. Although ritualistic behaviors are common among people with obsessive-compulsive disorder (OCD) and pathological gambling, other aspects of the conditions are different. For example, gambling has an ego-syntonic nature, meaning it is acceptable to or consistent with a person’s fundamental beliefs and personality, while the nature of compulsions in OCD are ego-dystonic or inconsistent with one’s beliefs. Biological differences also exist, including increased activity in the cortico-basal ganglionic-thalamic circuitry described during symptom-provocation studies of OCD and decreased activity in these regions of the brains of pathological gamblers, and the activation of the reward circuit observed in cue elicitation studies of pathological gamblers.^,

The association of pathological gambling with mood disorders has led to suggestions that it is an affective spectrum disorder. Many people who are pathological gamblers report that the pleasurable yet problematic behaviors alleviate negative emotional states. Because the behaviors are risky and self-destructive, the question has also been raised as to whether pathological gambling reflects subclinical mania or cyclothymia. Depression in individuals who are pathological gamblers may be distinct from primary or uncomplicated depression. That is, depression in people who are pathological gamblers may represent a response to financial difficulties, shame, and embarrassment. In addition, rates of co-occurrence of pathological gambling and bipolar disorder may not be as high as initially thought. Nonetheless, in some individuals who are pathological gamblers, brain-imaging studies have found regional differences in brain activity distinguishing bipolar subjects from controls and subjects who are pathological gamblers from controls when asked to perform a cognitive task involving attention and response inhibition.

Pharmacological Treatment of Pathological Gambling

Several medications have been studied as treatments for pathological gambling, and the range of medication classes—opioid antagonists, serotonin reuptake inhibitors (SRIs), mood stabilizers—that have been tested reflects the different ways pathological gambling is categorized (Table 1). Because no medication currently is approved by the Food and Drug Administration for treating pathological gambling, patients should be informed of off-label use of medications for pathological gambling, as well as the empirical basis for considering medication as a treatment.

Table 1

Pharmacotherapy Trials for Pathological Gambling-Double-Blind Trials

Opioid Antagonists

Pathological gambling and substance abuse have the following characteristics in common: 1) repetitive or compulsive engagement in a behavior despite adverse consequences, 2) diminished control over the problematic behavior, 3) an urge or craving prior to engagement in the behavior, and 4) a hedonic thrill when taking part in the behavior. These features have led to a description of pathological gambling as a behavioral addiction.

Dopaminergic systems that influence the rewarding and reinforcing behaviors involved in substance abuse also have been implicated in pathological gambling. Alterations in dopaminergic pathways have been suggested as the underlying cause of reward-seeking behaviors such as gambling and drug use. Gambling or using drugs then triggers the release of dopamine, which produces feelings of pleasure. Opioid receptor antagonists inhibit dopamine release in the nucleus accumbens and ventral pallidum through the disinhibition of gamma-aminobutyric acid (GABA) input to the dopamine neurons in the ventral tegmental area. Opioid antagonists are thought to decrease dopamine neurotransmission in the nucleus accumbens and the motivational neurocircuitry, thus dampening gambling-related excitement and cravings.

Given their ability to modulate dopaminergic transmission in the mesolimbic pathway, opioid-receptor antagonists have been tested as a possible treatment for pathological gambling. Initially, open-label treatment suggested the efficacy of naltrexone, an FDA-approved treatment for alcohol and opioid dependence, in reducing the intensity of urges to gamble, thoughts about gambling, and the behavior itself when given in high doses (range: 50 to 250mg/d; mean dose: 157 mg/d).

A 12-week double-blind placebo-controlled trial of naltrexone demonstrated superiority to placebo in 45 subjects who were pathological gamblers. Naltrexone (mean dose: 188mg/d) was effective in reducing the frequency and intensity of gambling urges, as well the behavior itself. A separate analysis showed that naltrexone was more effective in gamblers with more severe urges than in those who described their urges to gamble as moderate. Naltrexone’s clinical use, however, is limited by its side effects such as nausea as well as its tendency to elevate liver enzymes, especially in patients taking nonsteroidal anti-inflammatory drugs.

A recently completed multi-center study further demonstrated the efficacy of another opioid antagonist, nalmefene, in the treatment of pathological gambling. In a sample of 207 subjects, nalmefene demonstrated statistically significant improvement in gambling symptoms compared with a placebo in a 16-week double-blind trial. Although nalmefene, like naltrexone, causes nausea in some individuals, it was not associated with hepatotoxicity. In addition, nalmefene effectively reduced urges to gamble, thoughts about gambling, and the behavior itself among those subjects who received the drug compared with those who received the placebo.

Prescription Drug Costs

Antidepressants

The serotonin (5-hydroxyindole or 5HT) system has long been associated with impulse control. Evidence for serotonergic involvement in pathological gambling comes in part from studies of platelet monoamine oxidase B (MAO-B) activity, which correlates with cerebrospinal fluid (CSF) levels of 5-hydroxyindole acetic acid (5-HIAA, a metabolite of 5-HT) and is considered a peripheral marker of 5-HT function. Low CSF 5-HIAA levels have been found to correlate with high levels of impulsiveness and sensation- seeking behaviors. As compared with control subjects, pathological gamblers show diminished activation of the ventral medial prefrontal cortex (vmPFC) when watching gambling-related videotapes or performing the Stroop color-word interference task. Pathological gamblers also show relatively diminished activation of the vmPFC during a simulated gambling task; also, the severity of their gambling problem correlated inversely with the signal intensity within this region of the brain. Together, the findings suggest that decreased serotonin function within the vmPFC may engender disinhibition and contribute to pathological gambling. Thus, drugs targeting serotonin neurotransmission have been studied as a potential treatment of pathological gambling.

Data from double-blind randomized pharmacotherapy trials of SRIs, although promising, have been inconclusive. In a double-blind placebo-controlled study using sertraline, 60 subjects who were pathological gamblers were treated for 6 months (mean dose: 95mg/d). Sertraline did not prove to be superior to placebo. At the end of the study, 23 sertraline-treated subjects (74%) and 21 placebo-treated subjects (72%) were rated as responders based on the primary outcome measure, which assessed urges to gamble and gambling behavior.

Only two SRIs have been examined in at least two randomized, placebo-controlled trials for the treatment of pathological gambling. A double-blind, 16-week crossover study of fluvoxamine in 15 pathological gamblers showed a statistically significant difference compared with placebo in reducing urges to gamble. Interpretation of the study is complicated, however, by a phase-order treatment interaction (ie, the medication did not separate from the placebo during the first phase but did in the second phase). A 6-month double-blind placebo-controlled trial of fluvoxamine in 32 gamblers failed to show statistical significance compared with placebo. The result of the latter study, however, is complicated by the fact that only 3 subjects on the medication completed the study and that the investigators saw a high placebo response rate (59%).

As with fluvoxamine, studies have failed to demonstrate consistently the efficacy of paroxetine in treating pathological gambling. An initial double-blind, placebo-controlled study of paroxetine (average end-of-study dose: 52 mg/d) showed its potential efficacy as a treatment. Significant improvement was seen in subjects randomized to 8 weeks of treatment with the drug compared with those assigned to placebo. However, researchers failed to reproduce those results in a larger, 16-week multi-center double-blind placebo-controlled trial. At the end of the study, 48% of those assigned to placebo and 59% of those taking paroxetine were considered responders.

Several important findings emerge from these antidepressant studies. First, antidepressants, particularly those that influence serotonergic systems such as serotonergic reuptake inhibitors and possibly 5-HT1/5-HT2 receptor antagonists, may be effective in reducing the symptoms of pathological gambling. Second, as in the treatment of obsessive-compulsive disorder, the doses of antidepressants required to treat pathological gambling symptoms appear to be higher than those generally required to treat depressive disorders. Third, in studies in which participants had no or minimal symptoms of depression or anxiety, antidepressants were still effective in reducing gambling symptoms. The findings suggest that these drugs may target the serotonergic systems implicated in impaired impulse regulation. Response to antidepressants usually means fewer thoughts about gambling, less participation in the behavior, and improved social and occupational functioning. Patients may initially report feeling less preoccupied with gambling and less anxious about having thoughts of gambling.

Mood Stabilizers

In one study of fluvoxamine, two out of three nonresponders saw their condition worsen with drug treatment and were observed to have symptoms of cyclothymia. These findings suggested that alternate classes of drugs, such as mood stabilizers, might be helpful for some pathological gamblers. There has been only one randomized, placebo-controlled trial of a mood stabilizer tested in pathological gamblers. In a double-blind, placebo-controlled study of 40 pathological gamblers with bipolar spectrum disorders (bipolar type II, bipolar not otherwise specified, or cyclothymia), sustained-release lithium carbonate (mean lithium level: 0.87 meq/L) was shown to be superior to placebo in reducing gambling symptoms during 10 weeks of treatment. Those taking lithium reported statistically significant improvement in terms of having thought about gambling or having the urge to gamble. No difference was found, however, in the amount of money they lost, episodes of gambling per week, or time spent per gambling episode.

Clinical Approach to Pathological Gambling

The first and most important step in treating any disorder is to diagnose it properly. Many people are ashamed of the behaviors associated with pathological gambling and, therefore, may not report that they have a problem. For that reason, clinicians need to screen for pathological gambling if the disorder is to be treated properly. A diagnostic and treatment approach is presented in Table 2.

Table 2

Although pathological gambling has some shared characteristics with OCD, it also has important differences, and those differences may necessitate different treatment strategies. Many pathological gamblers also have substance abuse problems that may influence and interfere with the treatment of pathological gambling. Such conditions need to be addressed as well.

Subtyping pathological gambling based on clinical similarities to other disorders (eg, substance abuse), existence of co-occurring conditions (eg, bipolar disorder), or features of the behavior (eg, cravings), may be useful in deciding treatment interventions. Although subtyping of pathological gambling needs more research, early studies suggest that looking beyond the Diagnostic and Statistical Manual diagnostic criteria and examining what maintains the behavior may be helpful.

Although both pharmacological and psychosocial interventions have shown early promise for treating pathological gambling, no comparative studies have been done. Should treatment start with medication or therapy or both? Are there differences in individuals that may indicate a particular intervention might work better than others? More research needs to be done on such issues.

Given the pleasure associated with pathological gambling, motivating individuals to enter and adhere to treatment is difficult. High rates of treatment discontinuation (40% to 66%) are consistently seen among pathological gamblers. Rates of adherence to either psychosocial treatments or medication interventions are no better.

Conclusion

Pathological gambling has received little attention from clinicians and researchers. Despite prevalence rates similar to or greater than those for schizophrenia and bipolar disorder, much less research has been done on treatment strategies for this disorder. As a consequence, our understanding of efficacious and well-tolerated pharmacotherapies for pathological gambling lags significantly behind our understanding of treatment for other major neuropsychiatric disorders. Emerging data from controlled clinical trials, however, suggest that pathological gamblers frequently respond to pharmacological intervention.

Approaches reviewed in this article represent significant advances compared with what was available several years ago. It is hoped that progress in the treatment of pathological gambling will continue to be made at the same rate. Completion of additional, large-scale controlled studies of treatments for these disorders and comparative investigations of pharmacological agents are needed in order for physicians to offer more definitive treatment recommendations. Advances in these areas hold the potential for significantly improving the lives of pathological gamblers as well as those who are affected by their condition.

References

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