Everyone knows what anxiety is since each of us has already experienced some apprehension before an exam, when speaking in public, or when facing a challenging circumstance. Anxiety is a normal reaction to a threat, a constraint, or an unpredictable situation. In people with anxiety disorders, this reaction is excessive (too intense, too frequent, too long-lasting, no identified cause), disrupts normal daily life and, in the long term, has consequences on overall health.

Anxiety is characterized by emotional (fear, nervosity), cognitive (worries, excessive concerns, lack of concentration, uncontrollable thoughts, …) and behavioral (avoidance, restlessness, social withdrawal, …) symptoms often associated with physical manifestations (muscle tension and pain, pounding heart, insomnia, choking, etc.).

About 31% of persons with Parkinson’s disease have clinically significant anxiety disorders. It is much more than in the general population with a prevalence of 15 to 20%. The most frequent anxiety disorders in Parkinson’s disease are generalized anxiety, social phobia, agoraphobia, and panic disorder (see Table).

Moreover, persons with Parkinson’s disease may present atypical anxiety (fear of falling, excessive anticipation of OFF periods, …). The prevalence of atypical anxiety ranges from 13 to 30% but it is underrecognized since it does not match with usual diagnostic criteria.

PD-related anxiety disorders are more than understandable worry about the future in the context of chronic disease. They are reported at every stage of the disease, sometimes before diagnosis. Some patients, who were not particularly anxious before diagnosis, may develop PD-related anxiety disorders. In patients with anxiety traits before the onset of Parkinson's disease, the manifestations of anxiety will usually be exacerbated by the disease, increasing the difficulties coping with the symptoms of Parkinson's disease. With time, the progressive degeneration of neurons generally increases the frequency and intensity of anxiety episodes.

Anxiety may worsen motor (gait, freezing of gait, tremor, …) but also non-motor (sleep, cognition, urinary dysfunction, …) symptoms of Parkinson’s disease. Its impact is probably largely underestimated since many healthcare professionals, including general practitioners, are unaware that anxiety disorders are part of Parkinson's disease. Some people with Parkinson's disease do not understand that these changes are a result of their disease, making it even more difficult to talk about them. Others, influenced by stereotypes associated with mental health, fear being stigmatized by talking about it. The overlap with depression also makes the diagnosis more difficult. Overall, PD-related anxiety is underrecognized and often untreated.

Regarding treatment of PD-related anxiety, no drug has shown its effectiveness in a randomized controlled study. Adjustment of dopaminergic treatment can help. Serotonin reuptake inhibitors antidepressants are often used for anxiolytic purposes. Benzodiazepines are not recommended due to sedation, risk of falling, negative impact on cognition and habituation.  Nonpharmacological treatments may help. A recent randomized-controlled trial has shown that cognitive behavioral therapy significantly and sustainably reduces anxiety in Parkinson’s disease. Other complementary therapies have also shown some benefits: yoga, mindfulness, breath control. At a minimum, information and education of the patient and their caregiver must be undertaken to become aware that anxiety is a symptom of Parkinson’s disease with a possible negative impact on the other symptoms.

One of the main obstacles to the development of treatment for anxiety in Parkinson's disease is the lack of knowledge of the underlying mechanisms. Several works have shown the involvement of the dopaminergic and serotoninergic pathways in the occurrence of anxiety in Parkinson's disease. Degenerative lesions of Parkinson’s disease disrupt the limbic striatocortical circuit. The amygdala and the anterior cingulate cortex which are key structures in the neurocircuitry of fear playing a primary role in the processing of emotions seem also to be involved. Recent works have suggested that an imbalance between the fear and limbic circuits is at the origin of anxiety in Parkinson’s disease. Cognitive behavioral therapy with a focus on inducing brain plasticity could restore this balance. This opens the way to new therapeutic approaches aimed at restoring the correct functioning of these circuits.

Reference

[1] Broen MPG, Narayen NE, Kuijf ML, Dissanayaka NNW, Leentjens AFG (2016) Prevalence of anxiety in Parkinson’s disease: A systematic review and meta-analysis. Movement disorders, 31, 1125–1133

Kathy Dujardin is a neuropsychologist and Professor of Clinical Neuroscience in the Lille center of excellence in neurodegenerative diseases (LiCEND), at Lille University Medical Center and Guillaume Carey, MD is a neurologist at the University of Lille, France. Kathy Dujardin will be speaking at the WPC 2023 Congress in Barcelona. View the Scientific Program here.

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions or positions of the World Parkinson Coalition®