Melatonin therapy for REM sleep behavior disorder
Correspondence address: NoboruTakeuchi Department of Neuropsychiatry, Kurume University Hospital, 67 Asahi-machi, Kurume city, Fukuoka 830-0011, Japan. Email: firstname.lastname@example.org
Rapid eye movement sleep behavior disorder (RBD) is a parasomnia with clinical symptoms that include punching, kicking, yelling and leaping out of bed in sleep. Polysomnographic (PSG) finding showed REM sleep without muscle atonia. Clonazepam is generally used for treating RBD symptoms but melatonin was reported to be effective so we reconfirmed the effect of melatonin on RBD patients in the present study. We used melatonin (3–9 mg/day) which could ameliorate problem sleep behaviors remarkably, as well as %tonic activity in PSG variables. In the present study, melatonin was reconfirmed to be effective in RBD symptoms, especially for patients with low melatonin secretion, while its mechanism was not clearly known in the present study.
Rapid eye movement sleep behavior disorder (RBD) is a parasomnia, which is clinically characterized by vigorous sleep talking and violent behaviors such as punching, kicking, or sleepwalking, usually accompanied with vivid dreams during REM sleep.1 The most impressive polysomnographic (PSG) finding is REM sleep without muscle atonia. Treatment for RBD patients generally involves the usage of clonazepam, but melatonin has been recently reported to be effective to RBD symptoms by Kurz and Bes.2,3 We could then reconfirm efficiency of melatonin, performing detailed PSG and clinical course assessment.
SUBJECTS AND METHODS
Thirty patients were referred to our sleep disorder clinic with vigorous abnormal behaviors during the night. Detailed history taking and examinations including PSG, brain magnetic resonance image and blood test with 3 h interval melatonin concentration, were performed to confirm one sleepwalking and 29 RBD cases. Fifteen RBD patients (14 men and one woman; mean age 63.5 years) entered this study after giving their informed consent which included information about the efficiency and side-effects of melatonin. The initial dose of melatonin was 3 mg 30 min before bed time, with some patients being prescribed 6 or 9 mg according to the degree of their clinical symptoms. When their clinical symptoms were improved or stable, PSG and blood test including 3 h interval melatonin concentration were performed to detect melatonin efficiency to RBD symptoms and side-effects of melatonin. Polysomnographic findings were scored according to parameters of Rechtschaffen and Kales and submental electromyogram (EMG) without muscle atonia was separated into tonic REM and phasic REM activity, which were defined and calculated almost according to Lapierre and Montplaisir.1 In the present report, phasic REM activities were defined as any burst of EMG activity lasting 0.1–2 s with an amplitude exceeding 50 μV, and phasic REM activity was calculated per 2 s epoch. Tonic REM activity is defined and scored as more or less than 50% of the epoch (20 s epoch was defined as one epoch). %tonic EMG and %phasic EMG were percentage for all REM periods. We assessed whether melatonin was effective or not by clinical symptoms, melatonin concentration and PSG findings.
Thirteen patients and their partners noticed a suppressing effect on problem sleep behaviors after melatonin administration. Degrees of ameliorations could have classified (13 responders) as one mild, nine moderate and three remarkable (mild: 25% less vigorous sleep behaviors, especially when this involved the patients and their bedfellows in injury including ecchymoses, lacerations and fractures, when compared with before melatonin administration, moderate: 50% less, remarkable: 75% less), and the degree of their clinical course improvement revealed that efficacy of melatonin was dependent on dosage in some patients. We used paired t-test statistically, assessing sleep variables in PSG findings. %tonic REM activity in PSG findings was decreased after melatonin administration, but other sleep variables (Table 1) were not changed compared to those before melatonin administration. Melatonin could not change %phasic REM activity that clonazepam decreased phasic REM activity as stated in other reports. Melatonin concentrations in 10 RBD patients were under 30 pg/mL at maximal values, their mean 33.5 pg/mL in all 15 patients before melatonin administration, and RBD patients with low melatonin secretion tended to respond to melatonin therapy. Under melatonin therapy, their melatonin concentrations were over 1000 pg/mL at maximal values.
Table 1. Sleep variables
|Total in bed (min)||524.53 ± 14.01||512.33 ± 18.44||NS|
|Total sleep time (min)||402.3 ± 20.58||408.33 ± 21.19||NS|
|Sleep efficiency (%)||82.87 ± 2.48||85.26 ± 2.50||NS|
|Sleep latency (min)||44.47 ± 14.17||25.38 ± 3.85||NS|
|Wake time after sleep onset (min)||76.22 ± 11.66||70.64 ± 11.29||NS|
|REM latency (min)||119.96 ± 15.18||89.19 ± 8.2||NS|
|No. REM periods||3.93 ± 0.3||4.47 ± 0.27||NS|
|% Stage 1||26.86 ± 5.32||26.3 ± 4.17||NS|
|% Stage 2||49.86 ± 3.7||49.99 ± 3.75||NS|
|% Stage 3 + 4||8.7 ± 2.45||8.04 ± 2.29||NS|
|Stage REM (min)||73.58 ± 7.96||71.18 ± 6.81||NS|
|% Stage REM||17.23 ± 1.74||16.64 ± 1.55||NS|
|% Phasic REM activity||51.69 ± 42.27||7.64 ± 1.2||NS|
|% Tonic REM activity||16.43 ± 3.27||5.99 ± 1.41||< 0.01|
In the treatment of RBD, it is generally acccepted that the therapeutic efficacy of clonazepam is more closely involved in inhibition of the phasic REM activity than that of the tonic REM activity. Although melatonin is frequently used as a therapeutic agent for circadian rhythm disorders, there have been very few reports2,3 demonstrating favorable effects of this agent on RBD. Melatonin tended to remarkably improve RBD symptoms. Kurz and Bes hypothesized that melatonin might restore desynchronization to circadian rhythm on RBD symptoms, but the details of its mechanisms are currently not clear.3 We concluded melatonin was effective for RBD symptoms, while its detailed mechanism was clearly known. Melatonin might to be a useful alternative to clonazepam, especially for older patients, because few patients in this study noticed side-effects including muscle weakness and excessive morning sedation.