Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study.

To investigate the rate of and risk factors for restless legs syndrome (RLS) augmentation in Japanese patients receiving pramipexole (PPX) treatment. Records of 231 consecutive patients with idiopathic RLS who received PPX therapy for more than one month in a single sleep disorder center were analyzed retrospectively. Augmentation was diagnosed based on the Max Planck Institute criteria; associated factors were identified by logistic regression analysis. Mean age at PPX initiation was 60.6 ± 14.9 years and mean treatment duration was 48.5 ± 26.4 months. Augmentation was diagnosed in 21 patients (9.1%). Daily PPX dose and treatment duration were significantly associated with augmentation. By analyzing the receiver operating characteristic curve, a PPX dose of 0.375 mg/day was found to be the optimal cut-off value for predicting augmentation. After stratifying patients according to PPX treatment duration, at median treatment duration of 46 months, optimal cut-off values for daily doses were 0.375 and 0.500 mg/day for <46 months and ≥46 months of treatment, respectively. The RLS augmentation with PPX treatment in Japanese patients was occurred at rate of 9.1%, being quite compatible with previously reported rates in Caucasian patients. The symptom could appear within a relatively short period after starting the treatment in possibly vulnerable cases even with a smaller drug dose. Our results support the importance of keeping doses of PPX low throughout the RLS treatment course to prevent augmentation.

Prevalence of and Factors Associated With Sleep-Related Eating Disorder in Psychiatric Outpatients Taking Hypnotics.

OBJECTIVE: To clarify the prevalence and clinical features of sleep-related eating disorder (SRED) in psychiatric outpatients taking hypnotics as well as factors associated with the disorder. METHODS: From February 1, 2012, to February 29, 2012, a cross-sectional study was undertaken. A questionnaire addressing demographics, the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), presence of abnormal behavior during sleep focusing on SRED and sleepwalking, and duration of hypnotic medication and subjective side effects of the drug was distributed to psychiatric outpatients who were taking hypnotics at the time of the survey. RESULTS: Of 1,318 patients taking hypnotics, 1,048 patients (79.5%) provided valid responses, and 88 of them (8.4%) had experienced SRED. The SRED group was significantly younger, had a significantly higher total PSQI score, and took higher bedtime diazepam-equivalent doses of hypnotics than the non-SRED group (P < .01 for all comparisons). In the SRED group, subjective side effects due to hypnotics were present at significantly higher proportions than in the non-SRED group. Multiple logistic regression analysis showed that younger age (adjusted odds ratio [aOR] = 0.98, 95% CI = 0.96-0.99, P = .021), taking 2 or more kinds of antipsychotics (aOR = 3.41, 95% CI = 1.93-6.05, P < .001), and the bedtime diazepam-equivalent dose of a hypnotic (aOR = 1.03, 95% CI = 1.01-1.05, P = .039) were significantly associated with the experience of SRED. CONCLUSION: The prevalence of SRED in psychiatric outpatients taking hypnotics is elevated, particularly in younger patients, and the hypnosedative effects of the drugs could be responsible for the occurrence of the disorder in this population.

Comparison of clinical features between primary and drug-induced sleep-related eating disorder.

PURPOSE: The aim of this study was to ascertain the clinical characteristics of drug-induced sleep-related eating disorder (SRED). PATIENTS AND METHODS: We retrospectively reviewed the medical records of 30 patients with primary SRED (without any comorbid sleep disorders and who were not taking any possible causative medications), and ten patients with drug-induced SRED (occurrence of SRED episodes after starting nightly medication of sedative drugs, which completely resolved after dose reduction or discontinuation of the sedatives). RESULTS: All patients with drug-induced SRED took multiple types of sedatives, such as benzodiazepines or benzodiazepine receptor agonists. Clinical features of drug-induced SRED compared with primary SRED were as follows: higher mean age of onset (40 years old in drug-induced SRED vs 26 years old in primary SRED), significantly higher rate of patients who had total amnesia during most of their SRED episodes (75.0% vs 31.8%), significantly lower rate of comorbidity of night eating syndrome (0% vs 63.3%), and significantly lower rate of history of sleepwalking (10.0% vs 46.7%). Increased doses of benzodiazepine receptor agonists may be responsible for drug-induced SRED. CONCLUSION: The clinical features of drug-induced SRED were different from those of primary SRED, possibly reflecting differences in the underlying mechanisms between these two categories of SREDs.

Japanese version of the Munich Parasomnia Screening: translation and linguistic validation of a screening instrument for parasomnias and nocturnal behaviors.

OBJECTIVE: There is no broad screening instrument that can comprehensively assess parasomnias and sleep-related movement disorders listed in the International Classification of Sleep Disorders. The aim of this study was to develop the Japanese version of the Munich Parasomnia Screening (MUPS), a screening instrument for parasomnias and nocturnal behaviors, which was developed and validated at the Max Planck Institute of Psychiatry. METHODS: A multi-step translation methodology consisting of forward translation, back translation, expert review, and cognitive debriefing interviews was performed between June and November 2011. RESULTS: The English version of the MUPS was translated into Japanese, and the original author performed an expert review on the basis of a detailed report on the forward and back translation steps. The cognitive debriefing was carried out in five patients with parasomnia. The mean time to fill out the questionnaire was 8 minutes (ranging from 2 to 17 minutes). The authors reviewed and discussed the results of the cognitive debriefing interviews and modified the Japanese version. The final Japanese version was confirmed to be conceptually equivalent to the original English version. CONCLUSION: The Japanese version of the MUPS is an easy-to-use self-rating instrument for parasomnia and nocturnal behavior screening, consistent with the original version. The usage of this instrument would enable clinicians to quickly screen the past history and current frequency of nocturnal behaviors.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

BACKGROUND: Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. METHODS: In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. RESULTS: The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. CONCLUSIONS: Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

Impact of hypnotics use on daytime function and factors associated with usage by female shift work nurses.

OBJECTIVE: We investigated quality of life (QOL) and work performance of hypnotics users, and explored the factors associated with multiple hypnotics usage in shift work nurses. METHODS: We conducted a questionnaire-based, cross-sectional survey on nurses in university hospitals. We analyzed responses from 1202 nurses; 997 were female shift work nurses (82.9%), including 696 and 281 two- and three-shift workers, respectively. RESULTS: The rate of hypnotics use was 10% (6.9% were single hypnotic users and 3.1% were multiple hypnotics users). The rate of insomnia did not differ between the single and multiple hypnotics users. However, multiple hypnotics users showed lower QOL, more severe depressive symptoms, and greater frequencies of work-related errors than those using a single hypnotic. A multiple logistic regression analysis revealed that age ≥27 years, presence of depression, eveningness chronotype, and presence of insomnia symptoms were significantly associated with hypnotics use. On the other hand, only the existence of shift work disorder (SWD) was significantly associated with usage of multiple hypnotics. CONCLUSIONS: The present study suggested that usage of multiple hypnotics is not beneficial for relieving insomnia or for keeping better QOL in shift work nurses. It would be desirable to explore the causal relationship between SWD and multiple hypnotics use in a future longitudinal study.

The melatonin receptor agonist is effective for free-running type circadian rhythm sleep disorder: case report on two sighted patients.

Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients.

The validity of the PAM-RL device for evaluating periodic limb movements in sleep and an investigation on night-to-night variability of periodic limb movements during sleep in patients with restless legs syndrome or periodic limb movement disorder using this system.

BACKGROUND: The status of night-to-night variability for periodic limb movements in sleep (PLMS) has not been clarified. With this in mind, we investigated the validity of PLMS measurement by actigraphy with the PAM-RL device in Japanese patients with suspected restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) and the night-to-night variability of PLMS among the subjects. METHODS: Forty-one subjects (mean age, 52.1±16.1 years) underwent polysomnography (PSG) and PAM-RL measurement simultaneously. Thereafter, subjects used the PAM-RL at home on four more consecutive nights. RESULTS: The correlation between PLMS index on PSG (PLMSI-PSG) and PLM index on PAM-RL (PLMI-PAM) was 0.781 (P<.001). When the PLMSI cutoff value on PSG was set at 15 episodes per hour, the cutoff value for predicting this PLMSI level was 16.0 episodes per hour. When the condition was set to the level in which the mean interclass correlation coefficient reached ≥0.9, the number of required nights for repeated measurements was 26 nights for subjects with PLMI of <15 episodes per hour and three nights for those with PLMI ≥15 episodes per hour on PAM-RL. CONCLUSIONS: PAM-RL is thought to be valuable for assessing PLMS even in Japanese subjects. Recording of PAM-RL for three or more consecutive nights may be required to ensure the screening reliability of a patient with suspected pathologically frequent PLMS.

Differences in brain morphological findings between narcolepsy with and without cataplexy.

OBJECTIVE: Maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained by diffusion tensor imaging (DTI) can detect microscopic axonal changes by estimating the diffusivity of water molecules using magnetic resonance imaging (MRI). We applied an MRI voxel-based statistical approach to FA and ADC maps to evaluate microstructural abnormalities in the brain in narcolepsy and to investigate differences between patients having narcolepsy with and without cataplexy. METHODS: Twelve patients with drug-naive narcolepsy with cataplexy (NA/CA), 12 with drug-naive narcolepsy without cataplexy (NA w/o CA) and 12 age-matched healthy normal controls (NC) were enrolled. FA and ADC maps for these 3 groups were statistically compared by using voxel-based one-way ANOVA. In addition, we investigated the correlation between FA and ADC values and clinical variables in the patient groups. RESULTS: Compared to the NC group, the NA/CA group showed higher ADC values in the left inferior frontal gyrus and left amygdala, and a lower ADC value in the left postcentral gyrus. The ADC value in the right inferior frontal gyrus and FA value in the right precuneus were higher for NA/CA group than for the NA w/o CA group. However, no significant differences were observed in FA and ADC values between the NA w/o CA and NC groups in any of the areas investigated. In addition, no correlation was found between the clinical variables and ADC and FA values of any brain areas in these patient groups. CONCLUSIONS: Several microstructural changes were noted in the inferior frontal gyrus and amygdala in the NA/CA but not in the NA w/o CA group. These findings suggest that these 2 narcolepsy conditions have different pathological mechanisms: narcolepsy without cataplexy form appears to be a potentially broader condition without any significant brain imaging differences from normal controls.

Cognitive behavioural therapy with behavioural analysis for pharmacological treatment-resistant chronic insomnia.

This study aimed to determine whether (1) cognitive behavioural therapy with behavioural analysis for insomnia (CBTi-BA) is more effective for insomnia and co-morbid depressive symptoms than treatment as usual (TAU) and (2) whether CBTi-BA promotes earlier reduction of the daily dose of hypnotic medication in chronic insomnia resistant to pharmacological treatment. A total of 63 patients with chronic insomnia aged 20-77 years who already received hypnotic medication regularly were assigned to two interventions: combined therapy or TAU alone. The subjects provided demographic information and completed self-rating scales for insomnia and depressive symptoms. After treatment, the combined therapy group showed significant decreases in the symptoms of both insomnia and depression and significant reductions in the daily dose of hypnotic medication compared with the group receiving TAU alone. In the combined therapy group, 71% of the participants reported a reduction in insomnia to normal levels and 79% succeeded in decreasing the daily dose of hypnotics to 50% or less of the baseline dose. These results revealed that CBTi-BA can reduce insomnia and depressive symptoms as well as the daily dose of hypnotic medication in patients with chronic insomnia resistant to pharmacological treatment.

Is nocturnal panic a distinct disease category? Comparison of clinical characteristics among patients with primary nocturnal panic, daytime panic, and coexistence of nocturnal and daytime panic.

OBJECTIVE: Many patients with panic disorder (PD) experience nocturnal panic attacks. We investigated the differences in demographic variables and symptom characteristics as well as response to treatment among patients with primary day panic (DP), primary nocturnal panic (NP), and the coexistence of DP and NP (DP/NP), and discuss whether NP is a distinct disease category. METHOD: One hundred one consecutive untreated patients with PD were enrolled and subsequently divided into the NP, DP, and DP/NP groups. The presence of 13 panic attack symptom items as well as scores on the Panic Disorder Severity Scale (PDSS) and the Pittsburgh Sleep Quality Index (PSQI) were compared among the groups. After 3 months of regular treatment, PDSS scores were assessed again to evaluate treatment response. RESULTS: Nocturnal panic attacks of the participants were mostly reported to occur in the first tertile of nocturnal sleep. The number of males, onset age, and presence of choking sensation were significantly higher, and the PDSS score was significantly lower in the NP group compared with the other groups. The DP/NP group showed the highest PDSS score, and participants in this group were prescribed the highest doses of medication among all groups. Only diagnostic sub-category was significantly associated with treatment response. The total score for PDSS and PSQI correlated significantly only in the NP group. CONCLUSIONS: DP/NP could be a severe form of PD, while primary NP could be a relatively mild subcategory that may partially share common pathophysiology with adult type night terror.

Persistence of secondary restless legs syndrome in a phantom limb caused by end-stage renal disease.

Our patient had secondary restless legs syndrome (RLS) in the left lower limb caused by end-stage renal disease (ESRD). Severe RLS symptoms persisted even after amputation of the affected limb. Considering that oral administration of a dopamine receptor agonist was effective in treating the RLS in the phantom limb in this case, dysfunction of the central dopaminergic system was thought to be involved in the phantom limb-RLS mechanism. The persistence of RLS symptoms even after amputation of the affected limb suggests that the area responsible for ESRD-related RLS symptoms exists at the spinal level or in the higher central nervous system.