Objective: Investigate the effect of reducing anxiety using a known anxiolytic, alprazolam, on FOG symptoms severity and frequency. This reduction, in turn, might reduce the burden associated with FOG on PD patients and their caregivers.

Background: Freezing of gait (FOG) is a disabling and incapacitating motor symptom that results in falls and impairs the quality of life of more than 50% of later-stage Parkinson’s disease (PD) patients. FOG consists of brief episodes of an inability to initiate or continue walking and is characterized by short, stuttering steps, occurring particularly at gait initiation or upon turning. This symptom is relatively intractable, with minimal response to dopaminergic therapy. Anxiety worsens FOG.¹ This is consistent with patients’ subjective reports of anxiety during episodes of FOG, as well as the fact that stressful or anxiety-inducing situations seem to provoke FOG.^1,2

Method: PD patients with FOG (n = 10) completed two study sessions where we investigated the effect of alprazolam versus placebo, tested in counterbalanced order across participants. Both alprazolam (0.25mg) and placebo (i.e., cornstarch), were administered in identical capsules. During both sessions, participants completed standardized questionnaires assessing FOG, anxiety, and other cognitive and neurological abilities. Participants walked on a pressure sensitive walkway (Zeno^TM) in virtual environments that were designed to be either low- or high-anxiety settings. Virtual environments were created using WorldViz software and presented via Oculus Rift virtual-reality goggles.

Results: Preliminary results have shown an increase in the frequency of FOG episodes during high-anxiety trials compared to during low-anxiety trials following placebo administration. Additionally, alprazolam reduced the number of FOG episodes during high-anxiety trials. Moreover, administering alprazolam decreased measures of gait variability (stride length, stride time, and stride velocity variability) and increased swing time.

Conclusion: Our results support the contention that anxiety aggravates FOG in patients with PD. Additionally, we find that alprazolam, an anxiety-reducing medication, can reduce FOG symptoms. Moreover, one dose of a short-acting anxiolytic was able to ameliorate FOG symptoms, which provides promising preliminary evidence for future clinical trials on other anxiolytics with more prolonged duration to control FOG in patients with PD.

References: References: 1. Witt, I., Ganjavi, H. & Macdonald, P. Relationship between Freezing of Gait and Anxiety in Parkinson’s Disease Patients: A Systemic Literature Review. Parkinson’s. Dis. 2019, (2019). 2. Martens, K. A. E., Ellard, C. G. & Almeida, Q. J. Does Anxiety Cause Freezing of Gait in Parkinson’s Disease? PLoS One 9, e106561 (2014).

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