From the Department of Neurology, Oregon Health & Science University, Portland, OR.
Abstract
Objective: To review the clinical characteristics, epidemiology, and management of the most common neuropsychiatric symptoms (NPS) in Parkinson’s disease (PD).
Methods: Literature review.
Results: PD has traditionally been considered a disease of impaired motor function. However, neuropsychiatric complications, such as fatigue, depression, anxiety, psychosis, impulse control disorders, and apathy, frequently complicate the course of the illness. Although the development of new medication options in recent years has had a positive benefit on the management of these troublesome symptoms, responses are frequently suboptimal. The development of valid instruments to measure neuropsychiatric symptoms has been vital in research efforts to bridge the gaps in our understanding. Further elucidation of neuropsychiatric pathophysiologies will help to define treatment targets and has the potential to expand our therapeutic armamentarium.
Conclusion: While NPS affect patients with established disease, recent investigations have demonstrated risk of symptoms in those with early untreated stages of PD; therefore, better understanding of NPS should be the goal of practitioners treating the entire continuum of PD.
Parkinson’s disease (PD) has traditionally been considered a disease of impaired motor function, but increased recognition of nonmotor symptoms and in particular neuropsychiatric symptoms, such as fatigue, depression, anxiety, psychosis, impulse control disorders, and apathy, offer new opportunities for better care of patients. While neuropsychiatric symptoms affect patients with established disease, recent investigations have clearly demonstrated risk of symptoms in those with early untreated stages of PD; therefore, better understanding of neuropsychiatric symptoms should be the goal of practitioners treating the entire continuum of PD. This review will focus on the clinical characteristics, epidemiology, and management of the most common neuropsychiatric symptoms in PD.
Impulse Control Disorders
The recognition that dopaminergic drugs were successful at treating many symptoms of PD was followed by the disturbing realization that impulse control disorders could be an unfortunate side effect in a substantial minority. Impulse control disorders as defined by DSM-IV [1] are disinhibited behaviors that are maladaptive and recurrent, causing personal and relationship consequences. The impulse control disorders that became associated with PD and medication intake, particularly dopamine agonist use, included gambling, hobbyism, punding (stereotyped, seemingly purposeless behaviors), excessive sexual behavior, shopping, hoarding, and less commonly, compulsive eating. The prevalence estimates of these behavioral disturbances range from 6% to 15.5%, compared with < 2% in the general population [2,3]. The addiction-like dopamine dysregulation syndrome, whereby patients self-medicate with high doses of levodopa and short-acting dopamine agonists beyond what is needed for motor control, can lead to significant impairment of the therapeutic alliance in addition to other patient personal relations. With the advent of surgical options to treat PD and its medication complications, it was observed that stimulation of the subthalamic nucleus could be associated with the spectrum of impulse control disorders [4].
Epidemiology/Risk Factors
In a recent systematic review of the literature of impulse control disorders in PD [5], the authors determined that dopaminergic therapy caused compulsive or impulsive behaviors in approximately 10% of PD patients in the course of their treatment, with pathologic gambling and hypersexuality most frequently experienced. Multiple impulse control disorders are not uncommon and may coexist in one-quarter of patients with compulsivity. There appeared to be more disordered behavior with higher comparable doses of agonists. The authors concluded that impulse control disorder symptoms tended to occur with initiation or dose increases of direct D 2/D3 agonists, such as pramipexole and ropinirole. Importantly, impulse control disorder behavior improved if not resolved with discontinuation or reduction of dosage of the agonist, even if a compensatory levodopa dosage is added or increased. Perhaps not surprisingly, it was observed that if patients had a preexisting impulse control disorder prior to PD or the initiation of treatment, there was a high likelihood of worsening of symptoms. This small subgroup is estimated at about 1% of PD subjects, which corresponds to the prevalence of impulse control disorders in the general population. Other identified potential risk factors for impulse control disorder development include male gender, young age at onset, a personal or family history of addiction, novelty or risk seeking personality, and a concurrent diagnosis of depression [3]. In a recent study of early PD patients, the risk of developing an impulse control disorder became important once treatment with dopaminergic drugs began and continued for a year or more [6].
