Objective: To report a patient with Parkinson’s disease with freezing of gait and levodopa-induced dyskinesias who improved with zolpidem.

Background: A 57-year-old man developed Parkinson’s disease and was started on levodopa tablets, leading to excellent control of his symptoms. Later, he developed motor fluctuations: wearing off and dyskinesias. He was reluctant to undergo DBS surgery. At that point, he was using zolpidem controlled release on a PRN basis and noticed that this medication improved his symptoms, motivating him to try zolpidem during daytime. He started taking 6.25 mg TDS and started to experiencing longer ON periods free of dyskinesias.

Method: A motor symptoms diary showed that wearing off of levodopa changed from 3 to 4 hours after zolpidem, and time spent having dyskinesias reduced from 2 to 1 hour. He was also filmed, after zolpidem stride length improved, he experienced no freezing episodes and bradykinesia improved.

Results: Zolpidem is a GABAa receptor agonist, that induces inhibition of action potential. Improvement of PD motor symptoms, neuropsychiatric features, dyskinesias and gait initiation with zolpidem have been reported since the 1990s.⁴Improvement of tardive dyskinesia, dystonia, drug-induced parkinsonism and PSP have also been reported.^1,2,3,4,7 The only clinical trial conducted was a small double-blind placebo-controlled trial that showed that zolpidem improved the motor symptoms of PD.⁶ Both the GPi and the STN have a high density of GABAa receptors and both structures are overactive in PD. Zolpidem could be acting by selective reducing the overactivity of these structures.⁵ In-depth research on subtypes of GABA A receptor localization in basal ganglia circuits may clarify the use of new selective agonists, both in receptors’ synaptic mechanisms but also in extra-synaptic sites, which suggests long-term modulation, mainly at low doses, as found in this case.

Conclusion: After a brief time in the limelight, the field lost interest in zolpidem as a treatment for Parkinson’s disease. It is possible that side effects such as drowsiness prevented zolpidem from becoming a viable treatment alternative. More studies are needed to understand if zolpidem could be one alternative for patients who are unable to undergo deep brain stimulation and are troubled by motor fluctuations.

References: 1. Farver DK, Khan MH. Zolpidem for Antipsychotic-Induced Parkinsonism. Annals of Pharmacotherapy. 2001;35(4):435-437. doi:10.1345/aph.10214
2. Waln, O. and Jankovic, J. (2013), Zolpidem improves tardive dyskinesia and akathisia. Mov Disord., 28: 1748-1749. https://doi.org/10.1002/mds.25480
3. Huang HY, Hsu YT, Wu YC, Chiou SM, Kao CH, Tsai MC, Tsai CH. Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson’s disease after deep brain stimulation. Acta Neurol Taiwan. 2012 Jun;21(2):84-6. PMID: 22879118.
4. Daniele A, Panza F, Greco A, Logroscino G, Seripa D. Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease. Parkinsons Dis. 2016;2016:2531812. doi: 10.1155/2016/2531812. Epub 2016 May 17. PMID: 27293955; PMCID: PMC4886078.
5. J. Jankovic and C. D. Marsden, “Therapeutic strategies in Parkinsons’s disease,” in Parkinson’s Disease and Movement Disorders, J. Jankovic and E. Tolosa, Eds., pp. 95–119, Urban & Schwarzenberg, Baltimore, Md, USA, 1988.
6. A. Daniele, A. Albanese, G. Gainotti, B. Gregori, and P. Bar- tolomeo, “Zolpidem in Parkinson’s disease,” The Lancet, vol. 349, no. 9060, pp. 1222–1223, 1997.
7. E. Ruzicka, J. Roth, R. Jech, and P. Busek, “Subhypnotic doses of zolpidem oppose dopaminergic-induced dyskinesia in Parkinson’s disease,” Movement Disorders, vol. 15, no. 4, pp. 734– 735, 2000.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/controlled-release-zolpidem-improves-freezing-of-gait-and-levodopa-induced-dyskinesias-in-a-patient-with-parkinsons-disease/