Objective: A meta-analysis of alternative treatment therapies for refractory REM behavior disorder.

Background: Parkinson’s disease is a neurodegenerative syndrome that affects motor and non-motor functions. As many as 35% – 91.9% of patients diagnosed with rapid eye movement behavior disorder will later develop some form of neurodegenerative disease (St. Louis, Boeve, Boeve, 2017). In patients with neurodegenerative syndromes, up to 10% may struggle with refractory RBD (when conventional therapy of melatonin and clonazepam are ineffective) (St. Louis, Boeve, Boeve, 2017). RBD is an important nonmotor symptom to address because this can be disruptive to a restful night sleep but also places the patient and the bed partner at risk for physical injuries. Benzodiazepines like clonazepam must also be used in caution in patients with dementia, gait disorders, or concomitant obstructive sleep apnea (OSA).

Method: A literature analysis of a double blind cross over pilot trial of Rivastigmine was used for patients with refractory RBD in which melatonin and clonazepam has failed. Seroquel (Quetiapine) used in refractory RBD or patients that do not want to start a benzodiazepine. This will be considered for patients who waver with a more habit-forming agent such as a benzodiazepine (e.g., clonazepam). Pramipexole has also been used for the treatment of RBD. Most patients with neurodegenerative syndromes, particularly idiopathic Parkinson’s disease have been reported to have night symptoms (e.g., stiffness, tremor, RLS, and leg cramps) also suffer from RBD.

Results: The study showed an overall reduction in frequency of RBD episodes (reported by the sleep partners) (Di Giacopo, et al., 2012).In an informal trial of 10 patients were prescribed quetiapine 25mg – 50mg, 9 out of 10 patients have reported improved sleep and the sleep partners have reported a reduction in RBD episodes.

Conclusion: Further consideration should be made for the use of cholinesterase inhibitor (e.g., Rivastigmine), atypical antipsychotic (quetiapine 25-50mg), and dopamine agonist (Pramipexole 0.7mg TID) to help address refractory RBD. Additional trials with more patients may be needed to confirm the efficacy of these pharmacological treatment options. Treatment of RBD can help to prevent injuries to the patient and their bed partner. The most important treatment remains the reinforcement/discussion regarding a safe sleep environment in this patient population.

References: Aurosas, R. N., Zak, R. S., Maganti, R. K., Auerbach, S. H., Casey, K. R., Chowdhuri, S., Karippot, A., Ramar, K., Kristo, D.A., Morgenthaler, T. I. (2006). Best Practice Guide for Treatment of REM sleep behavior disorder (RBD). Journal of Clinical Sleep Medicine. Volume 6 (1); 85-89. Retrieved from: http://jcsm.aasm.org/ViewAbstract.aspx?pid=27717 Diederich, N.J., Goetz, C.G., Stebbins, G.T., et al. (2005). Repeated visual hallucinations in Parkinson’s disease as a disturbed external/internal perception: focused review and a new integrative model. Movement Disorder Society; 2: 130–140. Di Giacopo, R. D., Fasano, A., Quaranta, D., Marca, G.D., Bove, F., & Bentivoglio (30 January 2012). Rivastigmine as an alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Movement Disorder Society. Retrieved from https://doi.org/10.1002/mds.24909 Fantini, M. L., Ganon, J. F., Filipini, D., Montplaisir, J. (2003). The effects of Pramipexole in REM sleep behavior sisorder. Neurolgy. 61:1418-20. Schenck, C.H., Mahowald, M.W. (2002). REM sleep behavior disorder: clinical, developmental, and neuroscience perspective 16 years after its formal identification in sleep. Sleep; 25: 120–138. Schimdt, M.H., Koshal, V.B., Schmidt, H.S. (2006). Use of Pramipexole in REM sleep behavior disorder: results from a case series. Sleep Medicine. 7:418-23. St. Louis, E. K., Boeve, A. R., * Boeve, B. F. (2017). REM Sleep Behavior Disorder in Parkinson’s disease and Other Synucleinopathies. Movement Disorder Society. 32(5): 645 – 658. Doi 10.1002/mds27018.

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