Parkinson disease (PD) is a progressive neurodegenerative illness that is recognized clinically by its cardinal motor features: tremor, rigidity, and bradykinesia. However, it is increasingly clear that much of the suffering and disability associated with PD is caused by psychiatric disorders. Some of these seem to be intrinsic to PD and likely emerge from the same pathogenic process that gives rise to the motor symptoms. For example, depression, anxiety disorders, and dementia are all common in PD and likely occur because the same process that damages motor circuits can also affect brain regions that subserve mood and cognition. Other psychiatric problems are associated with PD because they are caused—at least in part—by the dopaminergic medications prescribed for motor symptoms. These include delirium, psychosis, and impulse control disorders.
Impulse control disorders, also described as “behavioral addictions,” include phenomena such as pathological gambling, compulsive shopping, hypersexuality (including paraphilic behavior), and binge eating. The failure to resist engaging in these behaviors rises to the level of a disorder when it causes distress or impaired occupational or social functioning. Such disorders often go un- recognized, only becoming obvious once they have wreaked havoc on the lives of patients and their families.
There may be a “Parkinson personality” characterized by cautious temperament and a decreased tendency to indulge in hedonic pleasures.1 Yet when treated with dopaminergic medication, a substantial portion of such patients have problems with an overzealous pursuit of pleasurable experiences. A better understanding of how this happens and why it happens in some but not others, might shed light on the underlying mechanisms of impulsivity and related behavioral disturbances in both persons with PD and the general population.
The association between impulse control disorders and PD seems to be driven by the dopamine replacement medications used to treat the motor symptoms of PD. A recent case-control study that compared 168 patients with newly diagnosed PD who had never received treatment with 143 healthy controls found no evidence for an increased prevalence of impulse control disorders.2 However, most studies that compare PD patients who are receiving treatment for their motor symptoms with healthy controls do find an increased prevalence of impulse control disorders in the PD patients. One cross-sectional study by Weintraub and colleagues3 of more than 3000 patients being treated for PD found a point prevalence of at least one impulse control disorder of 13.6%. The study looked specifically for pathological gambling (5.0%), sexual impulsivity (3.5%), impulse buying (5.7%), and binge eating disorder (4.3%) and found that 3.9% of patients engaged in more than one of these behaviors.
Impulse control disorders are much more common in patients who are receiving treatment with a dopamine agonist (such as pramipexole or ropinirole) than in patients treated only with the dopamine precursor levodopa. In the study by Weintraub and colleagues,3 17.1% of patients who were taking a dopamine agonist had an impulse control disorder compared with 6.9% of patients who were treated with levodopa.
The increased risk of an impulse control disorder developing during treatment with a dopamine agonist does not seem to be dose-dependent. Indeed, there have been reports of impulse control disorders in patients treated with dopamine agonists for conditions such as restless legs syndrome, for which these drugs are prescribed in substantially lower doses than in PD. By contrast, treatment with very high doses of levodopa seems to confer higher risk than treatment with low or moderate doses. Patients receiving treatment with both dopamine agonists and levodopa seem to be at the highest risk.3
Other risk factors for impulse control disorders in patients being treated for PD include having a personal or family history of impulse control disorders or addictions and having premorbid novelty-seeking or impulsive traits.4 There are sex differences in risk for particular impulse control disorders, with men more likely to engage in hypersexual behavior and women more likely to engage in impulse buying or binge eating.3 Other clinical factors that appear to be associated with impulse control disorders include depressive symptoms, irritability, and appetite changes.5
The motor symptoms in PD are caused by the destruction of dopaminergic neurons in the ventral portion of the substantia nigra pars compacta within the midbrain. These neurons project to the caudate and putamen and are involved in regulating motor function. This is the same system implicated in the extrapyramidal adverse effects of neuroleptics that block dopamine receptors. Medications for the motor symptoms of PD work by increasing dopaminergic neurotransmission within this circuit. Levodopa is a precursor to dopamine, while dopamine agonists act directly on dopamine receptors.
While dopaminergic neurons in the ventral part of the substantia nigra modulate motor circuits, other dopamine-producing neurons located in the dorsal part of the substantia nigra project to forebrain and limbic regions. These mesocortical and mesolimbic circuits are involved in voluntary driven behaviors through the assessment of and response to rewards and risks. While the ventral neurons are primarily destroyed in PD, the treatments for PD increase dopaminergic transmission in both sets of circuits. It is likely that excessive stimulation of dopamine receptors in limbic and forebrain regions contributes to the pathophysiology of impulse control disorders.6
Dr Taylor is a Psychiatry Resident at the Johns Hopkins Hospital in Baltimore. Dr Pontone is Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine in Baltimore. Dr Taylor reports no conflicts of interest concerning the subject matter of this article. Dr Pontone reports that he has received research support from the National Institutes of Health (NIH), the National Institute on Aging, the Michael J. Fox Foundation, and UCB (supplier of drugs and placebo for NIH-funded clinical trials); he has also provided expert testimony for Allergan.
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