Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study.

OBJECTIVE: To assess maintenance of efficacy and tolerability of gabapentin enacarbil in patients with moderate to severe primary restless legs syndrome (RLS). PATIENTS AND METHODS: This study (conducted April 18, 2006, to November 14, 2007) comprised a 24-week, single-blind (SB) treatment phase (gabapentin enacarbil, 1200 mg) followed by a 12-week randomized, double-blind (DB) phase. Responders from the SB phase (patients with improvements on the International Restless Legs Scale [IRLS] and investigator-rated Clinical Global Impression-Improvement scale at week 24 and stable while taking a gabapentin enacarbil dose of 1200 mg for at least 1 month before randomization) were randomized to gabapentin enacarbil, 1200 mg, or placebo once daily at 5 pm with food. The primary end point was the proportion of patients experiencing relapse (worse scores on the IRLS and investigator-rated Clinical Global Impression of Change scale on 2 consecutive visits at least 1 week apart or withdrawal because of lack of efficacy) during the DB phase. RESULTS: A total of 221 of 327 patients completed the SB phase, 194 (96 in the gabapentin enacarbil group and 98 in the placebo group) were randomized to DB treatment, and 168 (84 in the gabapentin enacarbil group and 84 in the placebo group) completed the DB phase. A significantly smaller proportion of patients treated with gabapentin enacarbil (9/96 [9%]) experienced relapse compared with the placebo-treated patients (22/97 [23%]) (odds ratio, 0.353; 95% confidence interval, 0.2-0.8; P=.02). Somnolence and dizziness were the most common adverse events. One death occurred (unintentional choking during the SB phase) and was judged as being unrelated to the study drug. No clinically relevant changes were observed in laboratory values, in vital signs, or on electrocardiograms. CONCLUSION: Gabapentin enacarbil, 1200 mg, maintained improvements in RLS symptoms compared with placebo and showed long-term tolerability in adults with moderate to severe primary RLS for up to 9 months of treatment.

Potentially lethal behaviors associated with rapid eye movement sleep behavior disorder: review of the literature and forensic implications.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of the muscle atonia of REM sleep, with release of complex and violent behaviors that are often attempted dream-enactments. This study reviewed the literature on RBD with regard to potentially lethal behavior. A total of 39-41 clinical cases of RBD associated with potentially lethal behaviors to self and/or others were found, involving a child and adults of all age groups, that manifested as choking/headlock (n = 22-24), defenestration/near-defenestration (n = 7), and diving from bed (n = 10). A total of 80.8% (n = 21) were males; 19.2% (n = 5) were females; mean age was 65.6 +/- (SD) 13.8 years (range: 27-81 years, and a child). (Gender/age data were not listed in the remaining cases.) An etiologic association of RBD with a neurologic disorder (or with pharmacotherapy of psychiatric disorders, n = 4) was present in 21-23 patients. Thus, RBD carries well-documented, potential forensic consequences during RBD episodes that could possibly have been misinterpreted as suicidal or homicidal behavior.

Sleep complaints in the geriatric patient.

Difficulty sleeping is a frequent complaint of elderly patients. But poor sleep is not a normal part of aging. This article discusses the most common sleep problem among older adults-insomnia, its causes, and potential treatments including over-the-counter and prescription medications and behavioral treatments such as relaxation therapy, sleep hygiene, stimulus control, sleep restriction, and cognitive and behavioral therapies.

Pathophysiologic mechanisms in REM sleep behavior disorder.

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 characterized by the absence of REM atonia, permitting the appearance of dream-enacting behaviors. These oneiric behaviors may be violent or injurious. RBD typically affects men over the age of 50 years. Longitudinal follow-up has shown that the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative disorders, most notably one of the synucleinopathies (Parkinson's disease, dementia with Lewy body disease, multiple system atrophy, or pure autonomic failure), often after a prolonged interval lasting more than 10 years. RBD is also a common manifestation of narcolepsy. RBD may be induced by medications, especially the tricyclic antidepressants and serotonin-specific reuptake inhibitors. In most cases, clonazepam is a highly effective treatment.

Analysis of interaction of acute atrial overdrive pacing with sleep-related breathing disorder.

Dose-related effects of atrial overdrive pacing (AOP) on sleep-related breathing disorder (SRBD) were studied. Fourteen patients with pacemakers with moderate to severe SRBD (mean screening apnea-hypopnea index [AHI] 35.2 +/- 21.9 events/hour) were randomized to 3 levels of pacing (50, 10, and 20 beats/min greater than the mean nocturnal heart rate) and studied by polysomnography, observing for changes in AHI. At the 2 AOP levels, no significant change was observed in the primary end point of reduction in AHI. Additionally, there was no observed impact on secondary end points of the study. Cyclic variation of heart rate was progressively abolished with higher levels of AOP without affecting AHI. Large variations were observed between the screening and control studies in SRBD indexes in a number of patients. In conclusion, AOP demonstrated no benefit to predominantly obstructive SRBD disorder of at least moderate severity.

Parasomnias: clinical features and forensic implications.

Parasomnias are undesirable behavioral or experiential phenomena arising from the sleep period. Once felt to be a unitary phenomenon, it is now clear that a wide variety of sleep disorders are capable of resulting in complex behaviors arising during sleep. The most common are disorders of arousal and rapid eye movement sleep disorder. Less common conditions include nocturnal seizures and psychogenic dissociative states. Malingering and Munchausen syndrome by proxy, while they are not actually parasomnias, may masquerade as parasomnias. Careful clinical and sleep laboratory evaluation can usually provide an accurate diagnosis with effective therapeutic implications. Due to the potential forensic implications, sleep medicine specialists may be asked to participate in legal proceedings resulting from sleep-related violence. An awareness of the spectrum of such behaviors, and their clinical and legal evaluation, is becoming more important in the practice of sleep medicine.