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Biology and Medicine

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Treatment of Pathological Gambling With Clomipramine. Eric Hollander, Maxim Frenkel, Concetta DeCarla, Sari Trungold, and Dan J. Stein. American Journal of Psychiatry 149:5, 710-711. May 1992. One of the earliest reports of drug therapy for pathological gambling, this brief article reports on one case of successful treatment using clomipramine, a drug marketed for the treatment of obsessive-compulsive disorder. The patient in question also exhibited mild obsessive-compulsive personality features, suggesting that the drug might prove most useful in individuals with similar conditions.

Treatment of Pathological Gambling with Carbamazepine. Reinhard Haller, H. Hinterhuber. Pharmacopsychiatry 27, 129, 1994. The authors report on the successful treatment of a single patient with carbamazepine, a drug previously used for other impulse control disorders, panic disorder, anxiety, depression, and mania. Of particular interest is the patientâs history of unsuccessful conventional treatment: 14 months of behavior therapy, two years of psychoanalysis, and three years of Gamblers Anonymous. The patient discontinued gambling after two weeks of treatment and remained in complete remission through 30 months of treatment.

A Study of the Dopamine D2 Receptor Gene in Pathological Gambling. David E. Comings, Richard J. Rosenthal, Henry R. Lesieur, Loreen J. Rugle, Donn Muhleman, Connie Chiu, George Dietz, Radhika Gade. Pharmacogenetics 6, 223-234, 1996. The authors studied 222 pathological gamblers along with 714 members of a control group to determine if a variant of the DRD2 gene associated with substance abuse is also associated with pathological gambling. Fifty-one percent of the gamblers were found to have the variant in question compared to 26 percent of the controls, with higher percentages found in those gamblers with comorbid substance abuse. The authors conclude that "these results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviors."

Altered Dopamine Function in Pathological Gambling. C. Bergh, T. Eklund, P. Sodersten & C. Nordin. Psychological Medicine, Vol. 27, p473-475, 1997. Swedish researchers examined the dopamine levels of cerebral spinal fluids (CSF) in ten pathological gamblers compared with seven controls. The findings suggest that changes in dopamine levels play a role in the psychopathology of pathological gambling. Several questions remain to be answered: do dopamine level changes result from the influence of pathological gambling, are some people vulnerable to gambling as a result of a deficient dopamine level, or are both of these possibilities associated with a third independent factor?

Psychosocial Challenges of Responsible Gambling. Tiit Tammik. Sault College of Applied Arts and Technology, Sault Ste. Marie, Ontario, Canada. June 1997. A major part of this work lies in the premise that some people are "at risk" to develop cravings and addictions to activities that raise dopamine levels in their brain's "pleasure" centers. This "biosychosocial" perspective emphasizes the importance of interactions among all classes of relevant variables; genetic-biological, psychological and socio-cultural. The author believes risk-taking behavior is an integral part of our human nature and a market driven, consumer culture is not likely to send out messages encouraging restraint. We are bombarded with messages urging us to consume and immediately indulge our every need. Novelty seeking behavior, another aspect of our human nature, is cleverly exploited by gaming industry marketers, casino designers and designers of enticing gaming equipment and activities. Tammik implies that since gambling and gambling addiction are not going to go away, society needs to encourage "safe gambling", perhaps in ways similar to how it encourages "safe sex" and responsible use of alcohol.

Opioid Antagonists in the Treatment of Impulse-Control Disorders. Suck Won Kim. Journal of Clinical Psychiatry 59:4, p159-164, April 1998. Dr. Kim studied the use of opioid antagonist drugs, specifically naltrexone, for the treatment of impulse-control disorders including pathological gambling. This preliminary study found sustained positive results in several patients. The author cautions, however, that until the completion of clinical trials these results must be regarded as preliminary.

Short-Term Single-Blind Fluvoxamine Treatment of Pathological Gambling. Eric Hollander, Concetta DeCarla, Eduardo Mari, Cheryl M. Wong, Serge Mosovich, Robert Grossman, and Tomer Begaz. American Journal of Psychiatry 155:12, 1781-1783. December 1998. This article reports on a non-randomized clinical trial of the drug fluvoxamine. Of the 10 patients completing an 8-week trial, seven showed significant improvement. All seven were abstaining from gambling, and showed significant improvement on various measurement scales. The study did not continue past the 8-week trial period, and the authors caution that randomized trials and longer-term studies are needed to adequately assess the drugâs effectiveness.

Genetic Contribution to Pathological Gambling: Possible Association Between a Functional DNA Polymorphism at the Serotonin Transporter Gene (5-HTT) and Affected Men. Ignacio Pérez de Castro, Angela Ibáñez, Jerónimo Saiz-Ruiz and José Fernández-Piqueras. Pharmacogenetics 9, 397-400, 1999. It is increasingly recognized that there is a relationship between an individualâs genes and their likelihood of developing pathological gambling. Likewise, it is also becoming apparent that the relationship is complex, involving multiple genes. Genes affecting the processing of the chemical dopamine have previously been implicated; here, the researchers investigate a gene involved with serotonin. They find a significant relationship between pathological gambling and the serotonin transporter gene (5_HTT), but interestingly only in men. In a previous study, the authors found a stronger relationship with a dopamine-related gene for female pathological gamblers.

Studies of the 48 bp Repeat Polymorphism of the DRD4 Gene in Impulsive, Compulsive, Addictive Behaviors: Tourette Syndrome, ADHD, Pathological Gambling, and Substance Abuse. David E. Comings, Nancy Gonzalez, Shijuan Wu, Radhika Gade, Donn Muhleman, Gerard Saucier, Patrick Johnson, Ray Verde, Richard J. Rosenthal, Henry R. Lesieur, Loreen J. Ruggle, Warren B. Miller, and James P. MacMurray. American Journal of Medical Genetics (Neuropsychiatric Genetics) 88:358-368, August, 1999. The authors compared the genotypes of 737 individuals from control groups and and index group of 707 individuals exhibiting impulsive, compulsive, or addictive behaviors. Focusing on the dopamine D4 receptor (DRD4) gene, they found significant differences between the genotypes of the control and index groups for each of the four behaviors studied. They also conclude that the role of the DRD4 gene in impulsive, compulsive, and addictive behavior is more complex than previously suspected.

Common Genetic Vulnerability for Pathological Gambling and Alcohol Dependence in Men. Wendy S. Slutske, Seth Eisen, William R. True, Michael J. Lyons, Jack Goldberg, Ming Tsuang. Arch Gen Psychiatry 57:666-673, July 2000. The authors studied adult male twin pairs to assess the existence of a common genetic factor behind pathological gambling and alcohol dependence. They found a "significant but relatively modest" linkage. Previous studies of the same population have shown genetic linkages between alcohol dependence and nicotine and marijuana dependence as well. However, the authors caution that the modest degree of linkage suggests that there are risk factors that pathological gambling does not share with alcohol dependence.

Double-Blind Naltrexone and Placebo Comparison Study in the Treatment of Pathological Gambling. Suck Won Kim, Jon E. Grant, David E. Adson, and Young Chul Shin. Biological Psychiatry, 2001;49:914-921. This study involved 45 patients, half of whom were administered the drug naltrexone and half of whom were given a placebo. At the end of an 11-week trial, 75 percent of those taking naltrexone were rated as either much or very much improved on both a patient-rated and a clinician-rated Clinical Global Impression scale compared to only 24 percent of those on the placebo. The authors note that while the drug was clearly more effective than the placebo, this and other studies suggest that the placebo effect is significant. (An additional 23 subjects were eliminated from the study after showing a positive placebo response in the first week.) The greatest response to naltrexone was found in those with the highest level of urge symptoms - the drug seemed to both reduce the urge to gamble and the level of pleasure associated with the gambling experience.

Psychiatric Comorbidity in Pathological Gamblers Seeking Treatment. Angela Ibanez, Darlos Blanco, Elizabeth Donahue, Henry R. Lesieur, Ignacio Perez de Castro, Jose Fernandez-Piqueras, Jeronimo Saiz-Ruiz. Am. J. Psychiatry 158:10, 1733-1735. October 2001. An evaluation of 69 pathological gamblers admitted to a treatment program led to diagnosis of a comorbid psychiatric disorder in 62 percent of the gamblers. The most frequent diagnoses were personality disorders (42%), alcohol abuse or dependence (33%) and adjustment disorders (17%). The gamblers with a comorbid disorder had significantly higher South Oaks Gambling Screen scores than those without a comorbid disorder. Significant genetic differences between the two groups involving a dopamine receptor gene were also found.

A Twin Study of the Association Between Pathological Gambling and Antisocial Personality Disorder. Wendy S. Slutske, Seth Eisen, Hong Xian, William R. True, Michael J. Lyons, Jack Goldberg, and Ming Tsuang. Journal of Abnormal Psychology 2001, 110:2, 297-308. Using a sample of 7,869 men in 4,497 twin pairs, the authors found a significant association between pathological gambling and antisocial personality disorder; the odds of a lifetime diagnosis of antisocial personality disorder were determined to be 6.4 times greater among pathological gamblers than among non-pathological gamblers. They also found elevated rates of childhood conduct disorder among the pathological gamblers, suggesting that the personality disorder preceeded, and therefore was not caused by, the gambling behavior. The authors also concluded that "there probably is at least one genetic locus that jointly increases the susceptibility" for pathological gambling and antisocial personality disorder.

The additive effect of neurotransmitter genes in pathological gambling. D.E. Comings, R. Gade-Andavolu, N. Gonzalez, S. Wu, D. Muhleman, C. Chen, P. Koh, K. Farwell, H. Blake, G. Dietz, J.P. MacMurray, H.R. Lesieur, L.J. Rugle, and R. J. Rosenthal. Clinical Genetics 2001: 60:107-116. The authors identified 31 different genes that potentially play a role in pathological gambling and tested for the relationship between these genes and pathological gambling using results from 139 pathological gamblers and 139 members of a control group. Fifteen of the genes were found to have a significant relationship. While the contribution of any one of the genes appears to be small, they have an additive effect: the more of the ãriskyä genotypes an individual has, the greater their risk of developing a gambling addiction. Many of these genes, which involve a range of brain functions, are also implicated in disorders such as attention deficit hyperactivity disorder, alcoholism, tobacco dependence, oppositional defiant disorder, and conduct disorders.

Lithium and Valproate Treatment of Pathological Gambling: A Randomized Single-Blind Study. Stefano Pallanti, Leonardo Quercioli, Erica Sood, Eric Hollander. Journal of Clinical Psychiatry. 2002; 63(7): 559-564. Previous studies have found some relationship between pathological gambling and bipolar (manic-depressive) disorders. With this in mind, the authors treated 42 pathological gamblers with one of two drugs commonly used as mood stabilizers in bipolar patients. Results were promising; the groups of patients treated with either drug showed significant improvement over the course of the 14 week study. The authors caution, however, that a more extensive double-blind study is required to establish the effectiveness of these medications.

How to recognize and treat the pathological gambler Jon E. Grant and Suck Won Kim. Current Psychiatry. February 2002, 1(2): 38-44. While breaking no new research ground, this article provides a summary of the various pharmacotherapies currently in use for the treatment of pathological gambling.

Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. E. Driver-Dunckley, J. Samanta, and M. Stacy. Neurology 61:422-423. August, 2003. The authors reviewed records from 1,884 patients with Parkinson’s disease and found nine records indicating that the patient had developed a gambling problem leading to serious financial loss while undergoing treatment for their disease. All nine were found to have been taking high doses of dopamine agonist drugs, and in seven cases the gambling began within a month of an increase in the dosage. Additionally, seven achieved “sustained resolution” of gambling symptoms following a change in their drug regimen. The remaining two required additional psychiatric intervention.

An open-label trial of bupropion in the treatment of pathological gambling. D.W. Black. Journal of Clinical Psychopharmacology 2004: 24(1), 108-110. Black used the psychostimulant bupropion to treat ten subjects meeting criteria for pathological gambling. At the end of the treatment regimine, seven of the ten reported gambling symptoms as "very much improved" or "much improved" Bupropion is primarily used to treat attention deficit hyperactivity disorder (ADHD), and previous studies relating pathological gambling and ADHD led to Black's use of the drug. While the apparent success is impressive, the study used no control group, involved only a small number of participants, and lacked any follow-up after the eight-week treatment program.

 Pathological Gambling Caused by Drugs Used to Treat Parkinson Disease. M. Leann Dodd, Kevin J. Klos, James H. Bower, Yonas E. Geda, Keith A. Josephs, J. Eric Ahlskog. Archives of Neurology 2005; 62:1-5. September 2005. Mayo Clinic researchers observed 11 Parkinson disease patients who developed pathological gambling after taking prescribed dopamine agonist drugs. In each case the gambling problem was resolved after the drug use was discontinued. Six of the patients also developed other behavioral problems, including compulsive eating, increased alcohol consumption, increased spending, and hypersexuality.