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.
Because there is the lack of evidence-based treatments for anxiety in PD, we highlight 2 PD-specific anxiety disorders: internal tremor, and nonmotor “off” anxiety.
Internal tremor
Internal tremor is a sense of vibration in the axial and/or appendicular muscles that cannot be seen externally by the patient or examiner. It is not yet fully understood if this phenomenon is sensory, anxiety-related, related to subclinical tremor, or the result of a combination of these factors (ie, sensory awareness of a subclinical tremor that triggers or is worsened by anxiety). There is some evidence for subclinical tremor on electromyography, but internal tremor does not respond to antiparkinsonian medications in 70% of patients.24 More electrophysiological research is needed to clarify this phenomenon. Internal tremor has been associated with anxiety in 64% of patients and often improves with anxiolytic therapies.24
Although poorly understood, internal tremor is a documented phenomenon in 33% to 44% of patients with PD, and in some cases, it may be an initial symptom that motivates a patient to seek medical attention for the first time.24,25 Internal tremor has also been reported in patients with essential tremor and multiple sclerosis.25 Therefore, physicians should be aware of internal tremor because this symptom could herald an underlying neurological disease.
Nonmotor ‘off’ anxiety
Patients with PD are commonly prescribed carbidopa-levodopa, a dopamine precursor, at least 3 times daily. Initially, this medication controls motor symptoms well from 1 dose to the next. However, as the disease progresses, some patients report motor fluctuations in which an individual dose of carbidopa-levodopa may wear off early, take longer than usual to take effect, or not take effect at all. Patients describe these periods as an “off” state in which they do not feel their medications are working. Such motor fluctuations can lead to anxiety and avoidance behaviors, because patients fear being in public at times when the medication does not adequately control their motor symptoms.
In addition to these motor symptom fluctuations and related anxiety, patients can also experience nonmotor symptom fluctuations. A wide variety of nonmotor symptoms, such as mood, cognitive, and behavioral symptoms, have been reported to fluctuate in parallel with motor symptoms.26,27 One study reported fluctuating restlessness in 39% of patients with PD, excessive worry in 17%, shortness of breath in 13%, excessive sweating and fear in 12%, and palpitations in 10%.27 A patient with fluctuating shortness of breath, sweating, and palpitations (for example) may repeatedly present to the emergency department with a negative cardiac workup and eventually be diagnosed with panic disorder, whereas the patient is truly experiencing nonmotor “off” symptoms. Thus, it is important to be aware of nonmotor fluctuations so this diagnosis can be made and the symptoms appropriately treated. The first step in treating nonmotor fluctuations is to optimize the antiparkinsonian regimen to minimize fluctuations. If “off” anxiety symptoms persist, anxiolytic medications can be prescribed.21
