REM sleep behavior disorder (RBD) is a fascinating experiment in nature predicted by animal studies in 1964. A defining feature of REM sleep is active paralysis of all somatic musculature (sparing the diaphragm to permit respiration). RBD is characte
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Evaluation of the effects of paroxetine in the treatment of REM sleep behavior disorder Katsuyasu YAMAMOTO,1 Naohisa UCHIMURA,1 Mitsunari HABUKAWA,1 Noboru TAKEUCHI,1 Hiroharu OSHIMA,2 Masachika OSHIMA2 and Hisao MAEDA1 1 Department of Neuropsychiatry, Kurume, Japan University School of Medicine, Kurume Fukuoka, and 2Oshima Hospital, Miyaki Saga, Japan
Abstract In drug therapy for REM sleep behavior disorder (RBD), clonazepam has been conventionally used. This agent was discontinued in many patients however, because of carryover and side-effects, such as muscle relaxation. In this study we administered paroxetine (an SSRI currently used in Japan that inhibits REM sleep) and investigated its efﬁcacy. The subjects were 19 patients. After administration, RBD improved to a mild state in 11 patients and to a moderate state in 5. The results of this study show that paroxetine is effective for RBD.
Key words: paroxetine, REM sleep behavior disorder, treatment.
REM sleep behavior disorder (RBD) is a parasomnia that is clinically characterized by vigorous sleep talking, sleepwalking, and violent behavior such as punching or kicking. It is usually accompanied by vivid dreams. The pathophysiology of RBD remains to be clarified. The disorder is classified into symptomatic RBD, which follows disorders of the brainstem, such as Parkinson’s disease, and idiopathic RBD, which develops in elderly people without organic etiological factors. For drug therapy, clonazepam is administered as a first-choice drug.1,2 With many patients however, this agent was discontinued because of carryover and side-effects such as muscle relaxation. In this study we administered paroxetine (an SSRI currently used in Japan that inhibits REM sleep) and investigated its efficacy.
The 19 subjects (15 males and 4 females) were diagnosed as having idiopathic RBD according to the International Classification of Sleep Disorders (ICSD), with a mean age of 64.7 ± 7.8 years. The mean age at onset was 59.0 ± 7.3 years. Before going to bed, the patients were administered only paroxetine. Because they remembered no abnormal behavior, their partners recorded it. We evaluated the efficacy and side-effects of this agent at 1-month intervals after the start of administration. When the effects were insufficient, the dose was increased. Clinical symptoms before and after treatment were evaluated according to the ICSD severity rating (Table 1). Patients were also instructed to record the contents of their dreams, and dream changes were investigated.
Correspondence: Dr Katsuyasu Yamamoto, Department of Neuropsychiatry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan. Email: [email protected] Accepted for publication 25 January 2006
RESULTS All patients had severe RBD according to the ICSD severity rating. After the administration of paroxetine, RBD improved to a mild state in 11 patients and to a moderate state in 5 (Table 2). In three patients, severe
Table 1 Severity rating of RBD in the ICSD Mild Moderate Severe
The frequency of specific behavior during REM sleep is less than once a month. Discomfort for patients or their partners is less marked. The frequency of specific behavior during REM sleep is less than once a week to once a month or more. Usually, physical discomfort for patients or their partners is observed. The frequency of specific behavior during REM sleep is more than once a week. Physical disorders in patients or their partners are observed.
Table 2 The outcome in RBD after paroxetine treatment Age (years)
Severity rating of RBD in the ICSD. ‡Discontinuation of the medication.
RBD persisted. The side-effects included nausea in one patient, dizziness in another, and diarrhea in one. In two of three patients with side-effects, the administration was discontinued due to dizziness ans diarrhea, respectively. Concerning dream contents, the improvement of RBD changed dreams involving quarrels to gentle dreams, which made them difficult to remember. The mean dose of paroxetine was 22.1 mg.
DISCUSSION The results of this study show that paroxetine is effective for RBD. Several studies have reported that SSRI shortened REM sleep, prolonged REM latency, and increased the duration of REM sleep without atonia.3 In this study, we did not evaluate pretreatment or post-treatment polysomnograms (PSG); however, clinical improvement was achieved despite an increase in the duration of REM
sleep without atonia. This suggests that the action mechanism differs from that of clonazepam, which is reported to decrease the duration of REM sleep without atonia. Concerning the mechanism of action of paroxetine, this agent may decrease the amount of dream by suppressing REM sleep and may stabilize emotion via the serotonin nervous system, resulting in the disappearance of dreams involving quarrels. (Several studies have reported that paroxetine has the efficacy to weaken a nightmare resulting from post-traumatic stress disorder.4,5) We have had such an experience but we have an impression that the effect appears comparatively early. It is not over a level of a hypothesis that serotonin may act directly; we need more investigation into this aspect in the future. In this study, clinical symptoms were evaluated according to the ICSD severity rating, but a detailed evaluation was impossible in three grades. In clinical practice, we evaluated the improvement rating based on
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the patient’s diary of dreams and detailed information from the patient’s partner. In the future, criteria for the improvement rating and objective evaluation methods, such as actigrams, should be established. Furthermore, the pathophysiology of RBD and the mechanism of action of paroxetine should be investigated by night polysomnography before and after treatment in a larger number of patients.
2 Shenck CH, Hahowald MW. REM sleep parasomnias: Neurol. Clin. 1996; 14: 697–720. 3 Winkelman JW, James L. Serotonergic antidepressants are associated with REM sleep without atonia. Sleep 2004; 27: 317–21. 4 Davidson JRT. Treatment of posttraumatic stress disorder: the impact of paroxetine. Psychopharmacol. Bull. 2003; 37: 76–88. 5 Leskin GA, Woodward SH, Young HE, Sheikh JI. Effects of comorbid diagnoses on sleep disturbance in PTSD. J. Psychiatr. Res. 2002; 36: 449–52.
1 Hahowald MW, Shenck CH. REM sleep behavior disorder. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine, 2nd edn. WB Saunders: Philadelphia, 1994; 574–88.