Impulse Control and Related Disorders in Parkinson's Disease

Abstract

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Keywords: Compulsive; D3 receptor; Dopamine agonist; Dopamine agonist withdrawal syndrome; Dopamine dysregulation syndrome; Impulse control disorder; Impulsive; Mesocorticolimbic; Parkinson's disease; Pathological gambling; Punding.