Management of Depression in Parkinson’s Disease

A 68-year-old man with a 4-year history of Parkinson’s disease stable on levodopa and no previous psychiatric history was brought by his wife to the emergency department for worsening depression and suicidal ideation. Screening laboratory tests and chest x-ray were unremarkable. Per neurology consultation, the patient was at his baseline with respect to motor symptoms with no new neurological deficits. A head CT had recently been obtained, and repeat imaging was not indicated. He was subsequently admitted to the psychiatry service for management of his depressive symptoms. On admission, he was started on citalopram, which was slowly titrated to a maximum daily dose of 20 mg without any worsening of motor symptoms. Over the next 2 weeks, he reported improved mood without any further suicidal ideation. He was discharged home with outpatient psychiatry follow-up.

Parkinson’s disease is a chronic, progressive neurodegenerative disorder clinically diagnosed by a combination of cardinal motor signs: bradykinesia, resting tremor, rigidity, and postural instability. The pathological hallmarks of Parkinson’s disease include the loss of dopaminergic neurons within the substantia nigra and the presence of Lewy bodies, intracytoplasmic inclusions comprised mainly of alpha-synuclein (2). While the estimated prevalence for Parkinson’s disease has varied widely, a recent meta-analysis reported the worldwide prevalence to be approximately 0.3% in the general population, suggesting that there are 7.5 million people living with the disorder worldwide (3). The incidence has been found to rapidly increase in populations over 60 years of age, with a mean age at diagnosis of 65 years (2). A male predominance has also been observed in many but not all epidemiologic studies, suggesting that men may have a higher risk for developing the disease than women (3).

Among the neuropsychiatric complications of Parkinson’s disease, depression is one of the most common and is associated with increased disability and reduced quality of life. Depending on diagnostic criteria used, the estimated prevalence of depression in Parkinson’s disease has varied widely across studies, from 2.7% to more than 90%, with an average prevalence of about 35% (4). Factors that have been found to be consistently correlated with depression in Parkinson’s disease include early-onset, advanced progression of the disease, “atypical” parkinsonism, female gender, and a personal or family history of depression, as well as psychiatric comorbidities, including anxiety, apathy, psychosis, cognitive impairment, and insomnia (1). While the underlying mechanism remains unclear, depression in Parkinson’s disease is thought to result from a complex interaction of psychological, social, and neurobiological factors. For some patients, depressive symptoms may actually represent a prodromal syndrome presenting before motor symptoms become apparent (5). Although depression is common in the disease and increasingly recognized as adversely affecting disability and quality of life, depression in Parkinson’s disease remains under-recognized and undertreated in clinical practice (4).

Recognizing depressive symptoms in Parkinson’s disease can be challenging because the psychomotor slowing and blunted affect commonly seen in depression can resemble the bradykinesia and masked facial expression of Parkinson’s disease. Additionally, somatic features of depression such as decreased appetite, low energy, and sleep disturbances are commonly seen in patients with Parkinson’s disease who do not have depression. Furthermore, depression must be differentiated from apathy, which commonly occurs in Parkinson’s disease, is characterized by diminished motivation, and has significant overlap with depressive symptoms. A potentially useful discriminating feature is mood, which is negative in depression and neutral in apathy (6). It is important to remember that the differential diagnosis for depression is broad and includes other psychiatric disorders such as bipolar disorder, cognitive disorders, neoplastic processes affecting the central nervous system, metabolic and endocrine abnormalities, infections, hypoxemia, sleep disorders, medication side effects, and substance use, as well as hypoactive delirium caused by a variety of underlying illnesses.

The initial assessment of patients with Parkinson’s disease presenting with depressive symptoms should involve a comprehensive medical and psychiatric history, review of current medications, collateral information, and physical examination. Screening laboratory tests should include blood cell counts, complete metabolic panel, thyroid-stimulating hormone, and vitamin B12. Depending on the degree of clinical suspicion for other etiologies, such as substance use, sexually transmitted infections, and/or delirium, it may be necessary to check blood alcohol level, blood/urine toxicology, screens for HIV and syphilis, arterial blood gas, and chest x-ray. Head imaging, neurology consultation, and neuropsychological testing should also be considered as clinically indicated (see Table 1).

Once other etiologies have been considered and appropriately ruled out, a diagnosis of depression can be made clinically based on symptomatology. According to a 2008 study by Starkstein et al. (7), DSM-IV diagnostic criteria for major depressive disorder and dysthymic disorder have been validated for use in patients with Parkinson’s disease, while the categories of minor and subsyndromal depression likely need further validation for use in this patient population.

Although traditionally considered a purely motor disorder, Parkinson’s disease is increasingly recognized as a complex disease process with a wide array of neuropsychiatric complications. Depression is one of the most common neuropsychiatric complications of Parkinson’s disease; however, the current evidence guiding the treatment of depression in the disease is limited. Given the potential negative impact on motor disability and quality of life, it is important that clinicians consider and treat depression in patients with Parkinson’s disease. Further research is required to assess the efficacy and safety of both pharmacologic and non-pharmacologic treatments in order to better inform our management of depression in this disease.