Parkinson disease (PD) is the second most common neurodegenerative illness in the United States, affecting more than 1 million persons. Disease onset is usually after age 50 years. In persons older than 70 years, the prevalence is 1.5% to 2.5%.1 While the primary pathology involves degeneration of dopaminergic neurons in the substantia nigra, circuits important in emotion and cognition are also variably disrupted.
The physical aspects of PD, such as tremor, rigidity, and postural imbalance, are the defining characteristics of the disease and, understandably, they are the focus of most research and clinical care. However, PD has a much greater effect on patients’ lives than just physical impairment. Many nonmotor aspects of PD, including depression, drug-induced psychosis and impulse control disorders, cognitive impairment, anxiety, and sleep disturbances, are common and are associated with a variety of poor outcomes.2 These nonmotor symptoms complicate the clinical management of the disorder and are significant determinants of poor quality of life for patients and their caregivers.3
PD is in many ways the prototypical neuropsychiatric illness. It is defined by well-described neuropathological findings. However, the variability in the extent of disease in the brain, as well as the impact of medications with considerable CNS effects, influences the diverse psychiatric presentations that, in turn, are influenced by the stress of living with the illness. Because there is such a direct connection between brain dysfunction and psychiatric symptoms, there is hope that understanding the behavioral aspects of PD will lead to a better understanding of psychiatric illness in other populations.
Depression is among the most common neuropsychiatric disturbances found in patients with PD. Roughly 40% of persons with PD are depressed; half meet criteria for major depression and half meet criteria for less severe forms of depression, such as dysthymia.4 Depression is particularly important because in addition to personal suffering, it is associated with a faster progression of physical symptoms, a greater decline in cognitive skills and ability to care for oneself, and poorer treatment adherence and quality of life, as well as greater caregiver distress.5 In fact, compared with the motor disability of PD, depression was found to be more predictive of overall disability and distress.6
Many of the symptoms used to make a diagnosis of depression, including poor sleep, decreased energy, psychomotor retardation, and poor concentration, are seen in nearly all patients with PD and are more properly seen as direct manifestations of PD and not of depression. One very interesting finding is that the incidence of suicide is lower in patients with PD, despite the extremely high rates of depression.7
There has been considerable debate over the etiology of depression in PD. While many patients are demoralized about having a serious and progressive illness, there is a general consensus that there is something intrinsic to the neurobiology of the illness that increases the risk of depression.
Despite the prevalence of depression in patients with PD, there are few controlled, well-designed studies that direct treatment. In a randomized trial that compared nortriptyline, paroxetine controlled- release (CR), and placebo, nortriptyline was superior to placebo and paroxetine CR.8 The trial also established that treatment of depression leads to improvements in quality of life, sleep, and some aspects of cognition.9 Findings from a short-term, randomized, placebo-controlled pilot study suggest that both citalopram and desipramine are more effective than placebo.10
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