Alissa S. Higinbotham, MD Assistant Professor of Neurology Division of Parkinson’s Disease and Movement Disorders University of Virginia Medical Center Charlottesville, Virginia
Steven A. Gunzler, MD Senior Attending Physician, Neurological Institute Parkinson’s and Movement Disorders Center University Hospitals Cleveland Medical Center Associate Professor of Neurology Case Western Reserve University School of Medicine Cleveland, Ohio
Disclosures Dr. Higinbotham reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products. Dr. Gunzler receives research support from Amneal, Biogen, the Michael J. Fox Foundation, the National Institutes of Health, the Parkinson’s Foundation, and Teva.
In terms of nonpharmacologic options, cognitive-behavioral therapy (CBT) is likely efficacious, exercise (especially yoga) is likely efficacious, and repetitive transcranial magnetic stimulation may be efficacious.15,16 While further high-quality trials are needed, these treatments are low-risk and can be considered, especially for patients who cannot tolerate medications.
Apathy
Apathy—a loss of motivation and goal-directed behavior—can occur in up to 30% of patients during the prodromal period of PD, and in up to 70% of patients throughout the disease course.17 Apathy can coexist with depression, which can make apathy difficult to diagnose.17 Given the time constraints of a clinic visit, a practical approach would be to first screen for depression and cognitive impairment. If there is continued suspicion of apathy, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part I question (“In the past week have you felt indifferent to doing activities or being with people?”) can be used to screen for apathy, and more detailed scales, such as the Apathy Scale (AS) or Lille Apathy Rating Scale (LARS), could be used if indicated.18
There are limited high-quality positive trials of apathy-specific treatments in PD. In an RCT of patients with PD who did not have depression or dementia, rivastigmine improved LARS scores compared to placebo.15 Piribedil, a D2/D3 receptor agonist, improved apathy in patients who underwent subthalamic nucleus deep brain stimulation (STN DBS).15 Exercise such as individualized physical therapy programs, dance, and Nordic walking as well as mindfulness interventions were shown to significantly reduce apathy scale scores.19 SSRIs, SNRIs, and rotigotine showed a trend toward reducing AS scores in RCTs.10,20
Larger, high-quality studies are needed to clarify the treatment of apathy in PD. In the meantime, a reasonable approach is to first treat any comorbid psychiatric or cognitive disorders, since apathy can be associated with these conditions, and to optimize antiparkinsonian medications for motor symptoms, motor fluctuations, and nonmotor fluctuations. Then, the investigational apathy treatments described in this section could be considered on an individual basis.
Anxiety disorders
Anxiety is seen throughout the disease course of PD in approximately 30% to 50% of patients.21 It can manifest as generalized anxiety disorder, panic disorder, and other anxiety disorders. There are no high-quality RCTs of pharmacologic treatments of anxiety specifically in patients with PD, except for a negative safety and tolerability study of buspirone in which one-half of patients experienced worsening motor symptoms.15,22 Thus, the treatment of anxiety in patients with PD is similar to treatments in the general population. SSRIs and SNRIs are typically considered first-line, benzodiazepines are sometimes used with caution (although cognitive adverse effects and fall risk need to be considered), and nonpharmacologic treatments such as mindfulness yoga, exercise, CBT, and psychotherapy can be effective.16,21,23
