Objective: We investigated the effect of acutely reducing anxiety with the benzodiazepine, Alprazolam, on freezing of gait (FOG) in patients with Parkinson’s disease (PD).

Background: FOG is a disabling and incapacitating motor symptom that results in falls and impairs the quality of life of more than 50% of later-staged patients with PD. FOG consists of brief episodes of an inability to initiate or continue walking and is characterized by short and stuttering steps, occurring particularly at gait onset or upon changes in direction or speed of ambulation. This symptom is relatively intractable, with minimal response to dopaminergic therapy. Anxiety is associated with FOG (for a review see Witt et al., 2019). This is consistent with patients’ subjective reports of experiencing anxiety during episodes of FOG, as well as with the fact that stressful or anxiety-inducing situations provoke FOG (Martens et al., 2014).

Method: Ten patients with PD and FOG participated in the current study.   In two sessions, on separate days, patients walked on a pressure-sensitive walkway (Zeno^TM) in virtual environments, created using WorldViz software and presented via Oculus Rift virtual-reality goggles. Trials were designed to moderate or provoke anxiety. In the Low Anxiety (LA) LA condition, participants walked on a plank that appeared level with the floor. In the high-anxiety (HA) conditions, the plank appeared raised. Alprazolam (0.25mg) and placebo were administered in identical capsules, in separate sessions. We assessed the impact of anxiety (LA vs. HA) and Alprazolam-related anxiety reduction (Alprazolam vs. Placebo) on a modified version of the BAI, blood pressure (BP), heart rate (HR), the frequency of FOG, step velocity, step length, and swing time, as well as on the coefficients of variation of step length, step time, and step width.

Results: Alprazolam reduced objective measures of anxiety (i.e., systolic BP and HR). FOG was experienced only during the high anxiety conditions. Further, Alprazolam marginally significantly reduced the number of patients experiencing FOG in HA conditions. It increased swing time and reduced gait variability, which are associated with FOG.

Conclusion: Our results support a notion that 1) anxiety aggravates FOG in patients with PD, and 2) Alprazolam reduces anxiety and FOG, as well as improves gait parameters associated with freezing. Our research suggests that anxiety is a causal factor of FOG in PD

References: Preliminary results of this study were presented during MDS Virtual Congress 2021, September 17-22, 2021.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alprazolam-reduces-freezing-of-gait-and-improves-freezing-related-gait-measures/