MANAGEMENT OF ENDOCRINE DISEASE: Impulse control disorders in patients with hyperpolactinemia treated with dopamine agonists: how much should we worry?

Dopamine agonists (DAs) represent a cornerstone in the management of patients with hyperprolactinemia and have an important role in the treatment of neurologic disorders, including Parkinson’s disease and restless legs syndrome. A growing body of evidence has identified impulse control disorders (ICDs) as possible adverse effects of DA therapy. A variety of ICDs may occur in patients treated with DA, including compulsive shopping, pathologic gambling, stealing, hypersexuality and punding (repetitive performance of tasks, such as collecting, sorting, disassembling and assembling objects). These behaviors can have devastating effects on patients’ life and family. In the present review article, we summarize available data on ICDs in patients with hyperprolactinemia as well as other disorders. Possible risk factors for the emergence of ICDs in patients treated with DA are discussed and the putative pathophysiologic mechanisms underlying the development of ICDs in this setting are reviewed. In addition, strategies for the early identification and management of ICDs in patients on DA are discussed. In conclusion, a wide variety of ICDs can occur in patients treated with DA, including those with hyperprolactinemia. The development of ICDs can have serious implications for patients’ well-being and family. Endocrinologists and other physicians involved in the care of patients on DA therapy must be aware of this potential adverse effect, counsel patients regarding pertinent symptoms and regularly evaluate treated patients for the development of ICDs. Early detection of ICDs and discontinuation of DA therapy can mitigate the potential harms associated with ICDs in these patients.

Pathologic Behaviors Provoked by Dopamine Agonist Drugs: Gambling, Sex, Eating, and Spending

Dopamine agonists are synthetic medications that stimulate dopamine receptors. They are commonly used for treatment of Parkinson’s disease and in lower doses for restless legs syndrome. This drug class includes pramipexole (Mirapex), ropinirole (Requip), and the rotigotine patch (Neupro). These drugs have special properties, with unique adverse effects that are not intuitively associated with the drug. Hence, a brief chapter is devoted to these side effects. If the patient is not taking one of these medications, this chapter may be skipped. Several years ago clinicians recognized that pramipexole and ropinirole were associated with the development of pathologic gambling. Insidiously, a minority of people who were prescribed these medications began experiencing the desire to gamble, such as at casinos or online. For some, this was an exacerbation of prior tendencies, but for others this desire came out of the blue, with no prior gambling history. Other types of compulsive pathologic behaviors soon were also recognized in some people treated with these drugs. This included inappropriate hypersexual behavior (extramarital affairs, pornography) and compulsive spending, eating, drinking, or smoking. In many people, this behavior was completely out of character. The common element was the initiation of pramipexole or ropinirole. The behaviors did not develop immediately, but insidiously became apparent after the medication was slowly escalated into the therapeutic range. Patients and family were often oblivious to the behavior or relation to the drug until specifically asked about it in the doctor’s office. The common theme among these compulsive behaviors is that they are inherently rewarding human experiences. It became recognized that use of these dopamine agonist drugs by some people was associated with a pathologic drive to excessively engage in such activities as gambling, sex, eating, or spending. For affected people, this began to dominate their thoughts and actions. Who would think that a drug could drive specific hedonistic or rewarding behaviors? Experience in the clinic and published evidence, however, corroborates this risk. The two primary agents that have been implicated are pramipexole (Mirapex) and ropinirole (Requip). The rotigotine patch has also been associated with such behaviors, but apparently less frequently.

Dopamine Agonists and Pathologic Behaviors

The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

HOW LONG CAN YOU ENJOY BLACKJACK WITH 100 CHIPS?

Gambling-related research has implications in financial area understandings and applications. Researches in this area usually focus on pathology, risk-taking, decision-making and addiction. Few works have been done to demonstrate the distribution of the playing time before players go bankrupt. One problem is that it is difficult to get statistics in real world gambling. In this paper, we do simulations in a Blackjack game with a selected strategy. We find the distribution of playing time before players lose a certain amount of money as a power law distribution, indicating the existence of very long playing time players. We also find that double is the most important factor that causes the fat tail. Comparison shows that when removing double, split and three to two payoff, Blackjack goes back to a random walk. The increase of the number of decks somewhat decreases the average playing time. Our results may have pathologic gambling intervention implications.

Valproate and cognitive therapy combined treatment efficacy in pathological gambling

IntroductionValproate is used in psychiatry as a mood-stabilizer and has efficacy in controlling impulsivity, therefore it seems to be a useful pharmacologic agent in pathologic gambling.ObjectiveTo assess the efficacy of valproate in the treatment of pathologic gambling.MethodsA group of 13 patients, 9 male and 4 female, mean age 32.6, diagnosed with pathologic gambling, according to the DSM-IV-TR criteria, received treatment with flexible dose of valproate (600–1400 mg/day, mean dose 850 mg/day) and 2 times/week cognitive therapy sessions. Patients with other axis I and II conditions were excluded. Also, none of these patients received valproate or structured cognitive therapy prior to this trial. Patients were monitored for 3 months using monthly administered Gambling Symptoms Assessment Scale (G-SAS), Clinical Global Impressions (CGI) and 10 points self-evaluated Visual Analogue Scale (VAS).ResultsValproate was associated with a mean decrease of 10.5 points on G-SAS at week 12, compared to baseline (p < 0.05), while the CGI decreased with only 1.3 points (p = 0.122) and the VAS improved with 2.3 points (p < 0.05). The combined treatment was associated with good tolerability profile, since no drop-out was recorded in the study group due to side events and only 7 reports of mild and medium adverse events were recorded.ConclusionValproate treatment associated with cognitive therapy could be a useful strategy in the management of pathologic gambling. Valproate's tolerability profile is good and the cognitive therapy offer an opportunity to ventilate the negative automatic thoughts, emotional distress and low impulse control strategies.