Drug Helps Relieve Disrupted Night time Sleep in Narcolepsy.

Patients with narcolepsy who have disordered nighttime sleep benefited more from sodium oxybate (SXB) than from modafinil or placebo, according to a randomized trial that documented fewer shifts from sleep stage 2 to 4 or rapid eye movement (REM) to stage 1 or full wakefulness in patients receiving SXB.

“In this retrospective analysis, sodium oxybate appeared to improve polysomnograms and patient-reported measures of disrupted nighttime sleep in narcolepsy,” said Yves Dauvilliers, MD, PhD, from the Reference National Center for Narcolepsy at Gui de Chauliac Hospital in Montpellier, France.

“Disrupted nighttime sleep (DNS) is a clinically common complaint, occurring in almost all patients with narcolepsy,” he said. The important features of DNS are frequent shifts to lighter sleep, awakenings after sleep onset, and poor sleep quality. Researchers retrospectively analyzed data from a randomized trial to evaluate the effects of 3 common narcolepsy treatments.

SXB is approved for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. Polysomnography has suggested that SXB can also increase slow-wave sleep and reduce sleep fragmentation.

“There have been no data, however, related to sleep continuity or patient sleep quality ratings,” Dr. Dauvilliers noted.

The current study, therefore, evaluated the effects of narcolepsy treatment modalities on REM and non-REM sleep-shift changes and sleep quality by retrospective analysis of data from a phase 3 randomized trial.

The findings were presented here at the American Neurological Association (ANA) 2013 Annual Meeting.

Study Details

The study included 278 patients with narcolepsy who were randomly assigned to 1 of 4 treatment groups: SXB, 9 g/day; modafinil, 200 to 600 mg/day; the combination of the 2 agents; or placebo. Patients take 1 dose of SXB before going to sleep and must wake up during the night to take a second dose.

Polysomnograms and sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PSQI)— specifically, question 6 (“During the past month, how would you rate your sleep quality overall?”)—were obtained at baseline and at 8 weeks. The analysis was performed on the 222 patients with evaluable sleep stage and sleep-quality PSQI data.

SXB alone and in combination with modafinil was associated with significant reductions at week 8 in the number of shifts relative to baseline. The reductions with SXB and the combination were greater than those observed with placebo. Modafinil was not associated with any shift stage reductions at week 8, Dr. Dauvilliers reported.

In shifting from stage 2/3/4 REM to stage 1/wake sleep, the median change from baseline was –13.0 (from 40.9 at baseline) in patients receiving SXB alone (P < .001) and –11.5 with the combination (P < .001). No significant reductions in these shifts were observed with modafinil alone or placebo.

In shifting from sleep-stage REM to stage 1/wake, the median change from baseline was –7.0 with SXB alone (P < .001) and –5.0 with the combination (P = .001).

“With SXB, we saw a huge decrease in the number of shift stages and from REM to stage1/wake,” he noted.

Patient-reported sleep quality also significantly improved from baseline with SXB and SXB plus modafinil. The change from baseline was –0.46 with SXB (P < .001) and –0.48 with the combination (P < .001), while modafinil and placebo demonstrated little to no change.

Nausea, vomiting, and dizziness were significantly more common with SXB than with modafinil or placebo, and more treatment discontinuations occurred among patients taking SXB alone or in combination with modafinil.

“SXB improved sleep continuity and sleep quality, and we believe this makes for an improvement in daytime functioning,” Dr. Dauvilliers concluded.

SXB Should Not Be Misused

Session moderator Beth Ann Malow, MD, professor of neurology at Vanderbilt University and director of the Vanderbilt Sleep Disorders Center, Nashville, Tennessee, emphasized that the study was conducted in patients with narcolepsy, and the findings should not be extrapolated to the general population with sleep latency.

“This is an innovative study, looking at this drug in sleep latency, since its traditional use is for improving daytime sleepiness. But it’s important to realize that this is in narcolepsy, not the general population, and this drug has abuse potential,” Dr. Malow said.

“My concern would be that the results are extrapolated to a population where the drug is not FDA [Food and Drug Administration]-approved. We must make this distinction,” she added. “I’m not saying it doesn’t have a role, but we should be careful.”

Comorbidities Common in Narcolepsy.

Individuals diagnosed with narcolepsy have substantially higher rates of psychiatric and medical conditions than the general population, a new study shows.

“We found that 27% of persons with narcolepsy had a mood disorder, 37% were taking an antidepressant — 3 times higher than the general population — and anxiety disorders were also prevalent,” said Maurice M. Ohayon, MD, DSc, PhD, professor of psychiatry and behavioral sciences at Stanford University School of Medicine, and director of the Stanford University Sleep Epidemiology Research Center in California.

In addition, chronic medical conditions were also greatly increased, said Dr. Ohayon, who noted, “Individuals affected with narcolepsy represent a vulnerable segment of the population. However, we only have a partial understanding of this vulnerability.”

The high prevalence of both medical conditions and psychiatric disorders seen in association with narcolepsy needs to be addressed when developing a treatment plan, Dr. Ohayon concluded.

He presented the findings at the American Neurological Association (ANA) 2013 Annual Meeting here. They were also recently publishedin Sleep Medicine.

High Frequency of Psychiatric Conditions

The study examined psychiatric disorders and medical conditions associated with narcolepsy in 320 narcoleptic patients, who were compared with a sample of 1464 persons matched for age, sex, and body mass index.

Study participants were interviewed regarding sleep habits, health, medication, medical conditions, sleep disorders, and mental disorders using the Sleep-EVAL. Mental disorders were classified according to theDiagnostic and Statistical Manual, 4th edition.

A high proportion of narcoleptic patients reported psychiatric disorders, especially major depressive disorder and social anxiety disorder, which affected nearly 20% of these individuals, Dr. Ohayon reported.

Table. Proportion of Mental Disorders in Narcoleptics vs Matched Controls

Disorder Narcolepsy (%) Controls (%) Adjusted Odds Ratio P Value
Major depressive disorder 17.1 6.4 2.7 <.001
Bipolar disorder 8.5 1.9 4.6 <.001
Post-traumatic stress disorder 11.3 5.3 2.1 <.001
Social anxiety 21.1 8.7 2.4 <.001
Panic disorder 12.5 3.9 3.2 <.001
Agoraphobia 8.5 1.3 6.5 <.001
Simple phobia 5.2 1.3 4.1 <.001
Obsessive-compulsive disorder 3.7 1.0 3.8 <.001
Generalized anxiety disorder 5.5 1.7 3.3 <.001

Five medical diseases were also more frequently observed among narcoleptic participants: hypercholesterolemia, digestive diseases, heart disease, upper respiratory tract disease, and hypertension. The highest odds ratios were for diseases of the digestive system, which were noted in 16.3% of the narcoleptic population vs 5.0% of the controls, a 3-times-increased risk (P < 0.001), and for upper respiratory tract diseases, which were noted for 27.5% and 10.9%, respectively, for an odds ratio of 2.5 (P < 0.001).

“In addition, 34% of narcoleptics were obese, and this was with matching for body mass index in the study, and they are more likely to have hypercholesterolemia and hypertension than the general population,” Dr. Ohayon added.

He said that major depressive disorder mostly developed after the onset of narcolepsy (88%), while social anxiety was present before the onset of narcolepsy in about half the cases. He further noted that several comorbid conditions were autoimmune disorders, such as inflammatory bowel disease, asthma, and allergies.

Dr. Ohayon concluded, “We don’t know how to interpret these data. These are just facts, but we don’t know what they mean.”

Session moderator Louis Ptacek, MD, Howard Hughes Investigator in the Department of Neurology at the University of California, San Francisco School of Medicine, commented on the study for Medscape Medical News.

“The study is quite fascinating, given the statistical significance of the findings,” Dr. Ptacek said. “It’s not surprising that people who might be predisposed to psychiatric disorders could have these precipitated by a stressful event such as narcolepsy, though in some patients the psychiatric diagnosis preceded the narcolepsy. While it’s important to identify these comorbidities, we don’t yet understand the connection or causality yet, as the author pointed out.”

Source: Medscape.com

Neuroenhancement of Kids ‘Not Justifiable,’ Neurology Groups Say.

Neuroenhancement — the use of prescription drugs (e.g., stimulants) by healthy people in order to increase normal brain function — “is not justifiable” for children without diagnosed neurological disorders, according to a new position paper published in Neurology.

The paper also notes that for “nearly autonomous” adolescents, neuroenhancement is “inadvisable because of numerous social, developmental, and professional integrity issues.”

The authors offer a series of discussion points to guide physicians’ conversations with parents who request neuroenhancement medications for healthy children and teens.

The position paper is endorsed by the American Academy of Neurology, Child Neurology Society, and American Neurological Association.

Source: Neurology