T. Roth

Sleepiness in Parkinson's disease: a controlled study.

Sudden‐onset sleep episodes while driving have been reported in Parkinsons disease (PD) patients, and termed sleep attacks because they were reported to be irresistible and to occur without warning. We postulate that these episodes are due to excessive daytime sleepiness secondary to the high frequency of sleep disorders in PD patients and the sedative effects of dopaminergic medications. We assessed the frequency and relationship between excess daytime sleepiness and sleep episodes while driving (SE) in patients with PD. We evaluated 101 consecutive PD patients presenting to the Movement Disorder Center at the Mount Sinai School of Medicine using a questionnaire that incorporated a subjective estimate of sleepiness, the Epworth Sleepiness Scale (ESS) and information on disease severity and dopaminergic medications. One hundred age‐matched respondents without PD served as a control population. Excess daytime sleepiness was reported in 76% of PD patients compared to 47% of controls (P < 0.05). The mean ESS scores for PD patients was 9.1 ± 6.1 versus 5.7 ± 4.4 in controls (P < 0.001). ESS scores ≥10 were observed in 40.6% of PD patients compared to 19% of controls (P < 0.01) and 24% of PD patients had scores ≥15, compared to 5% of controls (P < 0.001). Sleep episodes while driving were experienced by 20.8% of PD drivers compared to 6% of control drivers (P < 0.05). The mean daily levodopa (L‐dopa) dose equivalent was 1,142 ± 858 mg in PD drivers who experienced a SE while driving compared to 626 ± 667 mg in those who had not (P < 0.05). Similarly, ESS was significantly greater in drivers with a SE than in those without (11.6 ± 6.4 vs. 8.4 ± 4.1; P < 0.05). Logistic regression analysis demonstrated that ESS and mean daily L‐dopa dose equivalents were predictors of sleep episodes while driving, whereas age, gender, disease severity, and individual dopaminergic agents were not. These findings support the notion that sleep episodes while driving in PD patients are related to excess daytime sleepiness and dopaminergic load. Physicians should advise and treat patients accordingly.

The sleep-wake activity inventory: A self-report measure of daytime sleepiness

The purpose of this study was to develop a valid multidimensional self-report measure of sleepiness. There were 554 subjects who completed the inventory. The structure of the Sleep-Wake Activity Inventory (SWAI) was derived from principal components analysis. The independent predictive strength of the factors was assessed by forward stepwise regression analysis with the average sleep latency on the Multiple Sleep Latency Test (MSLT) as the dependent variable. The scores on each of the factors were also compared by the level of sleepiness determined by the MSLT (pathological, diagnostic gray area, and normal). Factor analysis showed the existence of six factors on the SWAI (Excessive Daytime Sleepiness [EDS], Psychic Distress, Social Desirability, Energy Level, Ability to Relax and Nocturnal Sleep). The EDS factor was the best predictor of average MSLT. It was also able to differentiate pathological levels of sleepiness from both the diagnostic gray and normal levels of sleepiness. EDS factor scores were sensitive to changes in sleep physiology as improved scores followed normalization of sleep-disordered breathing. The SWAI was shown to be easy to complete, have a multi-dimensional structure, have a EDS factor useful in the prediction of average MSLT scores, be sensitive to differential levels of sleepiness, and change as a result of effective treatment.

Pharmacological Effects of Sedative-Hypnotics, Narcotic Analgesics, and Alcohol During Sleep

This article briefly reviews the well known effects of sedative-hypnotics, alcohol and narcotics on sleep. These drugs also have respiratory depressant effects, and the limited information about their effects on sleep-related breathing disturbances is reviewed. They exacerbate obstructive sleep apnea syndrome and have moderate to minimal effects on occasional apnea or hypopnea, but do not induce breathing disturbances de novo.

Relationship of Psychopathology to Insomnia in the Elderly

Three groups of 18 volunteers each (nine men and nine women) were selected on the basis of age and the response to a sleep status questionnaire. Younger subjects (mean age, 43.8 years) who complained of difficulty in falling asleep or in staying asleep or of awakening too early were compared for evidence of psychopathologic signs with older subjects (mean age, 68.5 years) who had sleep‐related complaints and with older subjects (mean age, 71.3 years) who did not have sleep‐related complaints. Older subjects with insomnia complained more frequently of having trouble staying asleep and of awakening too early (P < 0.05), whereas the younger subjects with insomnia complained primarily about difficulty in falling asleep (P < 0.005). On a short form of the Minnesota Multiphasic Personality Inventory (MMPI‐168), the number of elevated scores indicating pathologic disturbances (T score >70) was higher (p < 0.05) for the younger subjects with insomnia (2.5 high scores) than for older subjects with insomnia (0.7 high scores) or for older normal sleepers (0.4 high scores). These results imply that although in younger persons psychopathologic disorders often are associated with insomnia, psychopathic disorders usually are not the cause of insomnia in the elderly.

Amnesic Effects of Lormetazepam

Sixteen healthy men, age 18-35, each received lormetazepam (1.5 mg), flurazepam (30 mg), temazepam (30 mg) and placebo (double-blind in a Latin Square design) 30 min before bedtime for 2 consecutive nights followed by a 12 day washout between conditions. Three hours after drug (2.5 h after bedtime) subjects were awakened and administered a 16-item memory task. Fifteen minutes after the awakening subjects returned to bed, were instructed to go to sleep, and remained in bed for an additional 5.5 h. Immediately after the memory tasks, before returning to bed, subjects recalled almost all of the 16 items when placebo was administered before bedtime. Immediate recall was significantly poorer than placebo after temazepam and flurazepam, but not after lormetazepam. Morning recall was reduced significantly from the immediate nighttime level in each condition; this loss was smallest with placebo. All active drug conditions produced significantly greater amnesia than placebo. This amnesia was smallest after lormetazepam and greatest after temazepam, which differed significantly from each other. All active drugs significantly reduced latency measures of the return to sleep after the 15 min awakening; it was shortest with temazepam and longest with flurazepam. This study showed a relation between the hypnotic and amnesic effects of these drugs which is consistent with their pharmacokinetic properties.

Readaptation to the laboratory in long-term sleep studies

Readaptation to the sleep laboratory was assessed in 10 volunteers complaining of insomnia with polysomnographic evidence of disturbed sleep. After an initial 3-night adaptation to the laboratory, subjects slept in the laboratory on 2 consecutive nights per week for 10 weeks and were administered medication according to the following protocol: placebo, Week 1; triazolam (.5 mg), Weeks 2-7; and placebo, Weeks 8-10. Routine sleep recordings were obtained on all laboratory nights. Over the 10 weeks, there were no statistically significant differences (p >.05) between Nights 1 and 2 on the following sleep parameters: percentage wake time, percentage REM, latency to Stage 2, and number of awakenings. It was concluded that readaptation effects in long-term studies are relatively small. The minimal sleep disruption associated with readaptation does not outweigh the advantages of taking repeated laboratory samples of 1 or 2 nights.

Pharmacologic therapy for sleep-related breathing disorders

Sleep-related breathing disorders (SRBDs) are characterized by disruptions in normal breathing patterns, typically caused by increased upper airway resistance or diminished ventilatory drive. SRBDs are often accompanied by impairment in sleep continuity and wakefulness. The full spectrum of features associated with SRBD syndromes can be divided into three components, each of which can be a target for pharmacological intervention: the sleep-breathing event and its immediate physiological consequences; the adverse effects of these events on sleep continuity; and impairment in daytime waking function. A number of pharmacologic agents have been studied for their ability to reduce upper airway resistance or increase ventilatory drive. Other medications have been tested for their ability to treat one or more of the symptoms of sleep or wakefulness in SRBD patients. The purpose of this article is to provide a review of the status of research related to the pharmacologic treatment of SRBDs.