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Dan Chen,1 Paula Shaw,2 Daniel M Canafax,1,3 James Catesby Ware4 1XenoPort, Inc., Santa Clara, CA, USA; 2Charles River Northwest, Tacoma, WA, USA; 3Theravance Inc., South San Francisco, CA, USA; 4Division of Sleep Medicine, Eastern Virginia Medical School, Norfolk, VA, USA Objective: Symptoms of restless legs syndrome (RLS) usually occur during the evening and night time, resulting in disrupted sleep and subsequent daytime fatigue. This study compared simulated driving performance, alertness, and cognitive function between healthy subjects and patients with a diagnosis of RLS. Methods: Fifteen healthy subjects and 15 untreated RLS subjects were enrolled and completed two driving tests. The first test occurred at 4 PM followed by the second test at 8 AM the next morning. Outcome measures included lane position variability (LPV), speed variability, frequency of simulated crashes (off-road events or collision), and brake reaction time. Other assessments included visual analog scale (VAS) of alertness and the Brief Assessment of Cognition (BAC). Results: Overall, RLS patients and healthy subjects performed similarly on driving assessments. Two subjects within each group experienced off-road events. RLS patients had less alertness on the VAS than healthy subjects before and after driving assessments. Both groups scored similarly on the cognitive function assessments. Conclusion: Despite reported diminished alertness, RLS patients did not demonstrate impairment in driving or cognitive performance. Keywords: restless legs syndrome, simulated driving performance, cognitive function

Context Intermittent use (i.e., a few nights per week) of hypnotic medication is often recommended for the treatment of chronic insomnia despite an absence of efficacy and safety data using this regimen. Study objectives To evaluate the clinical efficacy and safety of intermittent pharmacotherapy for chronic insomnia. Design and setting Randomized, double-blind, placebo-controlled, parallel groups, clinical trial at six sleep research sites. Patients One hundred-sixty-three (115 women, 48 men; mean age 44.1+ SE. 0.9 years), DSM-IV-defined primary insomnia patients were randomized, 134 patients completed the study. Interventions Eight weeks of treatment with either zolpidem 10 mg or placebo. Patients were instructed to take medication when they felt they needed it, but at least three and no more than five times per week. Main outcome measures Investigator and Patient Global Ratings were the primary outcome variables. Secondary measures from daily questionnaires to assess efficacy, rebound insomnia and drug taking behavior. Results The Investigator's Global Rating indicated that intermittent use of zolpidem produced a significantly better therapeutic effect and significantly reduced insomnia severity throughout the 8-week study relative to placebo. Zolpidem was found to be effective in initiating and maintaining sleep on nights taken, as compared to placebo, based upon the Patient's Global Ratings and all subjective sleep variables. No evidence of rebound insomnia was found on nights that zolpidem was not taken. The number of nights a pill was taken did not differ between groups, nor did frequency of pill taking change in either group across the duration of the study. There were no significant effects of treatment upon quality of life or neurocognitive measures. Conclusions Zolpidem 10 mg is effective in treating insomnia when used intermittently, without evidence of discontinuation effects or increased frequency of pill taking.

OBJECTIVES: Differences between men and women potentially provide insight into the regulation sleep apnea events. This study, therefore, examined how apnea frequency and duration varied according to age, sex, and sleep stage in a clinical population. DESIGN: N A SETTING: N A PATIENTS: Patients were 215 women and 215 men referred to a sleep disorders center with symptoms of obstructive sleep apnea and matched for BMI. Apnea events were compared across three age groups (18-39, 40-59, and 60-88 years) in stage 2 and in REM sleep. INTERVENTIONS: N A RESULTS: In stage 2 sleep, young and middle aged women were similar averaging 15 and 13 apnea events per hour respectively. Men had significantly more events averaging 27 and 30 events per hour for the corresponding age groups. The apnea frequency doubled from middle age to older women, and the sex difference narrowed between the older males and females to a non significant difference (26 events per hour for women versus 34 events per hour for men). Apnea duration was significantly longer in men than in women. Stage 2 apnea duration increased significantly with age for men (20.1, 21.5, 23.8 s) and women (16.7, 18.3, 20.6 s) across the three age groups. This also occurred in REM sleep in for men (22.8, 26.5, 29.8 s) and women (19.3, 22.4, 26.6 s). CONCLUSIONS: Duration did not demonstrate the marked "menopausal effect" that there was for apnea frequency. Female gender and younger age conferred benefit primarily by preventing airway collapse (reduced apnea frequency) with less of an effect on apnea duration, i.e., the ability to end the apnea. Compared to stage 2 sleep, REM sleep reduced the differences between men and women in apnea frequency. One explanation may be that differences in muscle tone of the upper airway account for the sex differences in apnea frequency.

We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF>300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 mg/l in Native American and 151 μ/l in white men (p = 0.8256); mean SF was 55 μ/l in Native American women and 63 μ/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites. © Blackwell Munksgaard, 2006.

This study examined the effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence. Trazodone is a sedating antidepressant without anticholinergic properties. Nefazodone is a new antidepressant that is a structural analogue of trazodone but is less sedating. Buspirone is a nonsedating, nonbenzodiazepine anxiolytic with antidepressant properties. Nefazodone was compared to trazodone and buspirone in a double-blind, placebo-controlled crossover study in 12 normal healthy males. Nefazodone increased rapid eye movement (REM) sleep, whereas trazodone and buspirone suppressed REM sleep. The drugs only minimally affected other sleep stages. Trazodone increased total tumescence time by delaying the onset of detumescence; nefazodone increased total tumescence time only insofar as it increased REM sleep; buspirone did not change total tumescence time when compared to placebo. The results support a growing body of data indicating that not all antidepressants suppress REM sleep. The results also are consistent with the interpretation of an earlier study showing that trazodone prolongs penile tumescence during sleep as a result of its alpha-adrenergic blocking properties that suppress detumescence. Nefazodone, with less alpha-adrenergic blocking activity, did not abnormally penile tumescence beyond REM sleep.

Two patients complaining of insomnia had sleep-related periodic leg movements (nocturnal myoclonus) on polysomnographic evaluation. Both also complained of cold feet and had abnormal peripheral pulse examinations. Treatment with phenoxybenzamine, alpha-adrenergic blocker, normalized the peripheral pulse responses, reduced the complaint of insomnia, and reduced the sleep related leg movements but resulted in only mild sleep improvements. Peripheral pulse examinations of ten other patients with sleep-related periodic leg movements revealed abnormal responses in four. From these and other results, it is hypothesized that the sympathetic nervous system may mediate the periodicity of sleep related periodic leg movements.

The etiology of erectile failure is not always clear despite the fact that recordings of nocturnal penile tumescence (NPT) are used to detect patients with a significant organic component to their complaint. We recorded electrodermal activity in addition to NPT in 60 impotent patients. Normally more electrodermal activity occurs in stage 2 than in stage REM sleep. Despite a similar total amount of electrodermal activity, organically impotent patients tended to have less electrodermal activity in stage 2 and more in stage REM sleep than those with normal NPT. This difference was due to a subgroup of 15 organically impotent patients with less electrodermal activity in stage 2 than in stage REM sleep. Because of this difference in the pattern of electrodermal activity in relation to sleep stages, the results suggest a central nervous system change is related to impaired erectile capability and abnormal NPT in these cases.

Trimipramine, a sedating tricyclic antidepressant, and imipramine were compared on polysomnographic parameters during a 4-week double-blind trial in depressed patients with insomnia and anxiety. Trimipramine eliminated objective evidence of sleep disturbance. This was not the case with imipramine, although depression improved similarly in both groups. Subjects' sleep appeared unchanged or more disturbed at the end of the treatment with imipramine. For trimipramine, the major changes in sleep parameters occurred during the first week of drug administration and did not parallel the gradual changes seen in the measures of depression. Additionally, trimipramine did not suppress REM sleep even in a subgroup of six trimipramine patients who had short rapid-eye-movement (REM) sleep latencies during the placebo baseline period, even though their depression was alleviated. The data demonstrate that (a) antidepressants may vary in their effects on sleep, even though they have similar effects on depression; (b) REM sleep suppression does not necessarily accompany improvement in depression; and (c) reports of improved sleep by patients undergoing antidepressant therapy may not reflect improvement on objective measures of sleep. The different sleep effects suggest the possibility of different antidepressant pathways.

Despite apparent similar amounts of bruxism, two groups that had been evaluated polysomnographically differed dramatically in symptomatology. Patients with severe symptoms were referred to as the destructive bruxism group and were compared with (a) a group with sleep disturbance complaints who had bruxism and (b) a group of insomniac depressed patients chosen without regard to bruxism. It was hypothesized that not only the presence of bruxism during sleep but its pattern and sleep stage relationship were factors affecting clinical symptoms. The results indicated that the sleep stage relationship was an important factor. Patients with severe symptoms attributed to nocturnal bruxism were likely to have more bruxism in REM sleep than the other groups. These results if replicated prospectively would help explain some of the discrepancies in the literature concerning sleep stage relationship of bruxism, as well as help explain differences in symptomatology of bruxism patients.

Evaluations of nocturnal penile tumescence (NPT) and penile blood pressure were performed on (1) a group of nondiabetics with normal NPT, (2) a group of nondiabetics with abnormally diminished NPT, and (3) a group of diabetics with abnormally diminished NPT. The 12 subjects in each group complained of impotence. Analysis of blood pressure data taken before the NPT evaluation suggests the possibility of selective low arterial blood pressure in impotent patients who show no obvious signs of other vascular disorders.

Fifty male subjects were group-matched for age and socioeconomic status. Twenty of the subjects were diagnosed as having sleep apnea and 20 were diagnosed as having narcolepsy on the basis of sleep studies. The remaining 10 subjects served as normal controls. Differences among the groups were evaluated on the bases of two psychological instruments designed to assess personality characteristics and mood states. The findings suggest that narcoleptics and apneics both present discriminatively different psychological profiles than do normals. Moreover, personality characteristics of these two groups are distinguishable from one another. Apneics tend to be individuals with hypochondriacal and hysterical characteristics, whereas narcoleptics are more easily characterized by anxiety and social introversion. Both severity of psychological disturbance (mean Minnesota Multiphasic Personality Inventory elevations) and personality pattern (two-point codes) distinguish the groups. Key Words: Sleep apnea-Narcolepsy-Psychological profiles.