Factors contributing to U.S. parents' decisions to administer melatonin to children.

OBJECTIVE: Pediatric melatonin use is increasingly prevalent in the U.S. despite limited research on its efficacy and long-term safety. The current study investigated factors contributing to parents' decisions whether to give children melatonin. METHODS: Parents of children 1.0-13.9 years completed an online questionnaire on children's health, sleep, and melatonin use. Parents who reported giving melatonin to their child were asked open-ended follow-up questions on why their child takes melatonin and why they stopped (if applicable). Responses were assigned to categories through thematic coding. RESULTS: Data were analyzed on 212 children who either consumed melatonin in the past 30 days (n = 131) or took melatonin previously (n = 81). Among children who recently took melatonin, 51.1 % exhibited bedtime resistance and 46.2 % had trouble falling asleep. Parents most commonly gave children melatonin to: help them fall asleep (49.3 %), wind down before bedtime (22.7 %), facilitate changes in their sleep routine (17.5 %), and/or change their circadian rhythm (11.4 %). Parents stopped giving melatonin because their child did not need it anymore (32.0 %), experienced negative side effects (9.3 %), and/or concerns about health and safety (13.3 %). Finally, parents initiated melatonin use on their own (50.0 %), were encouraged by a friend or family member (27.4 %), and/or followed the recommendation of a health provider (48.1 %). CONCLUSIONS: Parents administered melatonin to children for a number of reasons and discontinued melatonin based on their own observations of a variety of effects. Parents frequently initiated use without the recommendation of a medical professional. Further research on indications and efficacy of melatonin and wider dissemination of guidelines are needed to help parents make informed decisions regarding children's sleep health.

Sleep timing is associated with self-reported dietary patterns in 9- to 15-year-olds.

OBJECTIVE: To examine sleep timing differences in self-reported dietary patterns of children and adolescents. DESIGN: Cross-sectional. PARTICIPANTS: Students aged 9-15 years (n=119, 11.7±1.3 years, 76% female) attending a summer program for the gifted. The upper and lower quartiles of reported midsleep time (weighted weekday-weekend average) were used to identify early (n=28) and late (n=27) sleep timing groups. METHODS: Sleep patterns were assessed via self-report. Participants also rated their likelihood to consume 9 different categories of food and drinks on a 5-point scale ranging from "no likelihood" to "high likelihood." Foods were grouped as follows: (1) sugary and caffeinated beverages; (2) high-energy-dense, nutrient-poor foods (ie, sugary, salty, fatty foods); and (3) low-energy-dense, nutrient-rich foods (ie, vegetables, proteins, carbohydrates, fruits). RESULTS: Midsleep time was 02:11±00:25 for the early and 06:14±01:00 for the late sleep timing groups. Participants reporting later sleep timing were more likely to consume sugary/caffeinated beverages and high-energy-dense, nutrient-poor foods throughout the day compared with their early sleep timing peers. The late vs the early sleep timing group also had a higher likelihood of overall consumption of foods and drinks from all categories into the evening and nighttime hours. CONCLUSION: Our findings indicate that children and adolescents who exhibit late sleep timing are more likely to make poorer dietary choices, which may have important implications for understanding pathways to adiposity and obesity risk during this sensitive period of development.

Development and psychometric evaluation of the Children's Sleep-Wake Scale.

OBJECTIVE: To describe the development and psychometric evaluation of the Children's Sleep-Wake Scale (CSWS), a caregiver-report measure of behavioral sleep quality in 2- to 8-year-old children. DESIGN: Five studies using independent samples were completed to generate, refine, and finalize the item pool, as well as to confirm the factor structure and to assess the reliability and validity of the CSWS. SETTING: Field. MEASURES: CSWS, sleep diary, and actigraphy. RESULTS: Confirmatory factor analysis supported the theoretically proposed 5-factor structure (Going to Bed, Falling Asleep, Maintaining Sleep, Reinitiating Sleep, Returning to Wakefulness). The final questionnaire included 25 items, with items rated on a 6-point scale (Never, Once in Awhile, Sometimes, Quite Often, Frequently-if not Always, and Always); higher scores indicate better sleep quality. We found excellent internal consistency reliability for subscales and the total scale (α = .81-α = .91), strong test-retest reliability (r = 0.67-r = 0.84; all P values < .001), moderate-to-strong correlations between CSWS subscale scores and corresponding parental diary ratings (r = 0.58-r = 0.72; all P values < .001), and weak-to-moderate correlations between CSWS subscales and actigraphic measures (r = 0.38-r = 0.61; all P values < .001). CSWS subscale scores discriminated 4 extreme groups, thus supporting the construct validity of the scale. CONCLUSION: These collective findings indicate that the CSWS has adequate reliability and validity for research instruments and suggest that it is a convenient tool for assessing behavioral sleep quality in preschool-aged and school-aged children.

The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of acute nighttime sleep restriction, wake time, and daytime napping.

The cortisol awakening response (CAR) is presumed critically important for healthy adaptation. The current literature, however, is hampered by systematic measurement difficulties relative to awakening, especially with young children. While reports suggest the CAR is smaller in children than adults, well-controlled research in early childhood is scarce. We examined whether robust CARs exist in 2- to 4-year-old children and if sleep restriction, wake timing, and napping influence the CAR (n = 7). During a 25-day in-home protocol, researchers collected four salivary cortisol samples (0, 15, 30, 45 min post-wake) following five polysomnographic sleep recordings on nonconsecutive days after 4 hr (morning nap), 7 hr (afternoon nap), 10 hr (evening nap), 13 hr (baseline night), and 16 hr (sleep restriction night) of wakefulness (20 samples/child). The CAR was robust after nighttime sleep, diminished after sleep restriction, and smaller but distinct after morning and afternoon (not evening) naps. Cortisol remained elevated 45 min after morning and afternoon naps. .

The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study.

STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. This study evaluated the tolerability and efficacy of armodafinil for > or = 12 months. METHODS: Patients with ES associated with treated OSA, SWD, or narcolepsy who completed one of four 12-week, double-blind studies were eligible for this multicenter, open-label study of > or = 12 months' duration of treatment with armodafinil (50 to 250 mg/day). Adverse events and other criteria of tolerability were monitored throughout the study. Efficacy assessments included the Clinical Global Impression of Change (CGI-C), Brief Fatigue Inventory (BFI), and Epworth Sleepiness Scale (ESS). RESULTS: Of 743 enrolled patients (474 with treated OSA, 113 with SWD, and 156 with narcolepsy), 57% of patients (420/743) completed 12 months or more of treatment. Discontinuations due to adverse events occurred in 13% of patients (95/743) during the initial 12-month period. Throughout the > or = 12-month study, adverse events were generally of mild-to-moderate intensity; headache (25% [180/731]), nasopharyngitis (17% [123/731]), and insomnia (14% [99/731]) were the most common. Modest increases were observed in vital sign measurements (blood pressure [3.6/2.3 mm Hg], heart rate [6.7 beats per minute]) across all patient groups; most of the changes occurred by month 3. Improvements from baseline in efficacy assessments started at month 1 and were maintained throughout the study. CONCLUSIONS: Armodafinil remained effective and was generally well tolerated. Increased monitoring of blood pressure may be appropriate in patients on armodafinil. Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.

A double-blind, placebo-controlled study of armodafinil for excessive sleepiness in patients with treated obstructive sleep apnea and comorbid depression.

OBJECTIVE: Treatment of excessive sleepiness in the context of obstructive sleep apnea (OSA) may be particularly difficult in those with depression because depression and/or antidepressant medications may cause sleepiness and fatigue in addition to that due to the OSA. This study evaluating armodafinil, a nonamphetamine wakefulness-promoting medication, is the first trial for treatment of excessive sleepiness in patients with treated OSA and comorbid depression. METHOD: Men and women with OSA diagnosed using International Classification of Sleep Disorders criteria being treated with continuous positive airway pressure and comorbid major depressive disorder or dysthymic disorder according to DSM-IV-TR criteria were enrolled into a 12-week, randomized, double-blind, parallel-group study between September 2007 and March 2009 at 60 outpatient sites. Patients maintained on stable monotherapy with a serotonergic antidepressant and with a 17-item Hamilton Depression Rating Scale score < 17 received placebo or armodafinil (target dose: 200 mg once daily). Coprimary outcomes were the proportion of patients with at least minimal improvement on the Clinical Global Impression of Change (CGI-C) as related to excessive sleepiness and mean change from baseline in Maintenance of Wakefulness Test mean sleep latency at final visit; the key secondary outcome was mean change in the Epworth Sleepiness Scale score. RESULTS: 249 patients were enrolled: 125 in the armodafinil group and 124 in the placebo group. The proportion of patients with at least minimal improvement on the CGI-C was statistically significantly greater in the armodafinil group (69%) compared with the placebo group (53%, P = .012). Mean (SD) increase in Maintenance of Wakefulness Test sleep latency was numerically but not significantly greater following armodafinil (2.6 [7.1] min) versus placebo (1.1 [7.6] min, P = .30) treatment. Mean decrease in Epworth Sleepiness Scale score was greater in the armodafinil group (-6.3 [4.8]) than in the placebo group (-4.8 [4.9], nominal P = .003). Headache, dry mouth, and insomnia were the most common adverse events occurring with armodafinil treatment. There was no clinically significant effect on depression in either group as measured by the Quick Inventory of Depressive Symptomatology-Self-Report 16. CONCLUSIONS: Armodafinil significantly improved overall clinical condition related to excessive sleepiness as rated by the CGI-C and was well tolerated in patients with treated OSA and comorbid depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00518986.

A case-control study of the environmental risk factors for narcolepsy.

BACKGROUND: Despite the acknowledged importance of environmental risk factors in the etiology of narcolepsy, there is little research on this topic. This study sought to fill this gap in the literature and assess the risk of stressors and infectious diseases using a case-control study. METHODS: Cases (n = 63) were recruited through the Stanford Center for Narcolepsy. All were HLA-DQB1*0602 positive, met conventional Multiple Sleep Latency Test criteria, and reported unambiguous cataplexy. Controls (n = 63) were nonrelated family members of cases and local community members. A self-administered questionnaire was used to assess the frequency and timing of possible risk factors. RESULTS: Of the infectious diseases examined, only flu infections and unexplained fevers carried a significant risk. Several of the stressors carried a significant risk including a major change in sleeping habits. When the timing of all risk factors was considered, exposure prior to puberty increased the risk for developing narcolepsy. CONCLUSIONS: These findings emphasize the importance of environmental risk factors in the etiology of narcolepsy. This highlights the need for further research on this aspect of narcolepsy so a complete understanding of a disorder that affects 1 in 2,000 individuals can emerge.

The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy.

OBJECTIVE: This study assessed the efficacy and safety of armodafinil, the longer half-life enantiomer of modafinil, for the treatment of excessive sleepiness in patients with narcolepsy. RESEARCH DESIGN AND METHODS: This was a multicenter double-blind study with 196 patients (aged 18-65 years) randomized to receive armodafinil 150 mg (n = 65), armodafinil 250 mg (n = 67), or placebo (n = 64) once daily for 12 weeks. MAIN OUTCOME MEASURES: Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) (six 20-min subtests across the day), the Clinical Global Impression of Change (CGI-C), subjective measures of sleepiness (Epworth Sleepiness Scale), patient diaries, and evaluations of cognitive performance (Cognitive Drug Research) and fatigue (Brief Fatigue Inventory). RESULTS: Armodafinil significantly increased MWT mean sleep latency (at 0900-1500) compared with placebo. The mean change from baseline at final visit for armodafinil was an increase of 1.3, 2.6, and 1.9 min in the 150-mg, 250-mg, and combined groups, respectively, compared with a decrease of 1.9 min for placebo (p < 0.01 for all three comparisons). Mean late-day MWT latency (1500-1900) was also significantly improved (difference of armodafinil combined group relative to placebo at final visit: 2.8 min, p = 0.0358). The proportions of patients who showed at least minimal improvement in the CGIC rating from baseline to final visit in the armodafinil 150-mg, 250-mg, and combined groups were 69%, 73%, and 71%, respectively, compared with 33% for placebo (p < 0.0001). Both doses were associated with statistically significant improvements in memory, attention, and fatigue (p < 0.05). The most common adverse events in patients receiving armodafinil were headache, nausea, and dizziness. CONCLUSIONS: Armodafinil significantly improved ability to sustain wakefulness throughout the day in patients with narcolepsy. Armodafinil also significantly improved overall clinical condition, memory, attention, and fatigue when compared with placebo.

Modafinil facilitates performance on a delayed nonmatching to position swim task in rats.

Modafinil is a wake-promoting drug approved by the FDA for the treatment of narcolepsy. Recent evidence suggests that modafinil may improve learning and memory processes. To further evaluate possible cognitive properties associated with modafinil, male Sprague-Dawley rats were tested in a delayed nonmatching to position (DNMTP) task. A modified water maze allowed animals to make one of two choices for the location of the escape platform. Each trial consisted of two swims. On the information swim (IS), only one choice was open to the animal for escape. One minute later, a choice swim (CS) presented the animal with two choices with the escape platform in the opposite position. There were 10 trials per day for 10 days. Rats received 0, 30, 55, or 100 mg/kg ip of modafinil 30 min prior to testing. Locomotor activity was also assessed. Animals that received 55 and 100 mg/kg made significantly more correct choices, indicating that higher doses of modafinil learned the task faster than did controls. While animals that received 100 mg/kg did exhibit an enhancement of locomotor activity, this effect did not result in more efficient goal-directed behavior. The evidence is consistent with previous research showing that modafinil facilitates cognitive processes.

The month-of-birth pattern in narcolepsy is moderated by cataplexy severity and may be independent of HLA-DQB1*0602.

OBJECTIVES: A March peak and a September trough in the birth pattern of narcolepsy patients with clear-cut cataplexy was recently reported. The objectives of the present study were to determine whether the month-of-birth pattern would (a) vary with the presence and severity of cataplexy and (b) differ for patients positive and negative for HLA-DQB1*0602. DESIGN: Cross-sectional survey with data obtained from the clinical trials assessing the safety and efficacy of modafinil in the treatment of narcolepsy. SETTING: Sleep clinics throughout the United States. PATIENTS: A group of 530 narcolepsy patients diagnosed based on the International Classification of Sleep Disorders using clinical histories, nocturnal polysomnography, and Multiple Sleep Latency Tests. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: A surplus of March births and a fall-off in September births was found in narcolepsy relative to the general population. This finding was only observed when cataplexy was moderate or severe. The month-of-birth pattern was similar for HLA-DQB1*0602 positive and negative patients. A March birth and HLA-DQB1*0602 positivity were independent risk factors in a logistic regression analysis. CONCLUSIONS: Environmental events during development may influence narcolepsy severity or the likelihood of developing the disease.