Katherine M. Sharkey

Effects of melatonin administration on daytime sleep after simulated night shift work

Disturbed sleep and on‐the‐job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep‐promoting and circadian phase‐shifting effects. This study was designed to isolate melatonin’s sleep‐promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo‐controlled, double‐blind, cross‐over design. Subjects (n=21, mean age=27.0 ± 5.0 years) participated in two 6‐day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8‐h night shifts followed by 8‐h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained‐release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep‐promoting effects of melatonin across more than 1 day needs further investigation.

Evaluation and Management of Sleep Disturbance during the Menopause Transition

Sleep disturbances in midlife women are common and have been associated with the menopause transition itself, symptoms of hot flashes, anxiety and depressive disorders, aging, primary sleep disorders (i.e., obstructive sleep apnea, periodic limb movement disorder), comorbid medical conditions and medications, as well as with psychosocial and behavioral factors. Because there are several common sources of sleep problems in midlife women, the cause of an individual womans sleep disturbance may be multifactorial. Effective behavioral and pharmacological therapies are available to treat sleep disturbances of different etiologies. This review provides an overview of different types of sleep disturbance occurring in midlife women and presents data supporting the use of hormone therapy, hypnotic agents, and behavioral strategies to treat sleep problems in this population. The review aims to equip clinicians evaluating menopause-age women with the knowledge and evaluation tools to diagnose, engage sleep experts where appropriate, and treat sleep disturbance in this population. Sleep disorders in midlife women should be treated because substantial improvements in quality of life and health outcomes are achievable.

Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints.

OBJECTIVES Opioid-dependent patients treated with methadone have subjective sleep complaints and disrupted sleep on polysomnography (PSG). Previous studies of sleep-disordered breathing (SDB) in this population have focused on central sleep apnea (CSA). Our objectives were to: (1) characterize obstructive sleep apnea (OSA) and CSA in patients in methadone maintenance treatment (MMT) for opioid dependence; (2) examine factors associated with SDB in this population; and (3) investigate whether SDB was related to severity of subjective sleep complaints in MMT patients with subjective sleep disturbances. METHODS We analyzed OSA and CSA from one night of home PSG in 71 patients who were in MMT for at least 3 months and had a Pittsburgh Sleep Quality Inventory (PSQI) score >5. RESULTS OSA (defined as obstructive apnea-hypopnea index (OAHI) > or = 5) was observed in 35.2% of our sample. OSA was associated with higher body mass index, longer duration in MMT, and non-Caucasian race. CSA (defined as central apnea index (CAI) > or = 5) was observed in 14.1% of the sample. CSA was not associated with methadone dose or concomitant drug use. Subjective sleep disturbance measured with the PSQI was not related to OSA or CSA. CONCLUSIONS SDB was common in this sample of MMT patients and OSA was more common than CSA. Given the lack of association between presence of SDB and severity of subjective sleep difficulties, factors other than sleep apnea must account for complaints of disturbed sleep in this population.

Sleep Duration, Insomnia, and Coronary Heart Disease Among Postmenopausal Women in the Women's Health Initiative

BACKGROUND Long and short sleep duration are associated with increased risk for coronary heart disease (CHD) and cardiovascular disease (CVD); however, evidence is inconsistent. We sought to identify whether self-reported sleep duration and insomnia, based on a validated questionnaire, are associated with increased incident CHD and CVD among postmenopausal women. METHODS Womens Health Initiative Observational Study Participants (N=86,329; 50-79 years) who reported on sleep at baseline were followed for incident CVD events. Associations of sleep duration and insomnia with incident CHD and CVD were evaluated using Cox proportional hazards models over 10.3 years. RESULTS Women with high insomnia scores had elevated risk of CHD (38%) and CVD (27%) after adjustment for age and race, and in fully adjusted models (hazard ratio [HR]=1.19, 95% confidence interval [CI] 1.09-1.30; 1.11 95% CI 1.03-2.00). Shorter (≤5 hours) and longer (≥10 hours) sleep duration demonstrated significantly higher incident CHD (25%) and CVD (19%) in age- and race-adjusted models, but this was not significant in fully adjusted models. Formal tests for interaction indicated significant interactions between sleep duration and insomnia for risk of CHD (p<0.01) and CVD (p=0.02). Women with high insomnia scores and long sleep demonstrated the greatest risk of incident CHD compared to midrange sleep duration (HR=1.93, 95% CI 1.06-3.51) in fully adjusted models. CONCLUSIONS Sleep duration and insomnia are associated with CHD and CVD risk, and may interact to cause almost double the risk of CHD and CVD. Additional research is needed to understand how sleep quality modifies the association between prolonged sleep and cardiovascular outcomes.

Heterogeneity of postpartum depression: a latent class analysis

BACKGROUND Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. METHODS Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17,912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. FINDINGS 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10·5), followed by those in class 2 (mean EPDS score 14·8) and those in class 3 (mean EPDS score 20·1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20·1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). INTERPRETATION PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. FUNDING Sources of funding are listed at the end of the article.

Assessing sleep in opioid dependence: a comparison of subjective ratings, sleep diaries, and home polysomnography in methadone maintenance patients.

OBJECTIVES Comparisons of subjective and objective sleep measures have shown discrepancies between reported sleep and polysomnography (PSG) in non-drug dependent individuals with and without insomnia. Sleep may affect behavioral and physiologic aspects of drug abuse and dependence; patients in methadone maintenance therapy (MMT) for opioid dependence frequently report sleep problems. Whether subjective sleep reflects objective sleep in MMT patients is unknown. We undertook these analyses to establish the correlations among subjective and objective sleep measures in MMT patients. METHODS We compared one week of daily sleep diaries, one night of home PSG, a questionnaire completed the morning after PSG, and the Pittsburgh Sleep Quality Inventory (PSQI) as well as demographics and drug use measures in 62 MMT patients with disturbed sleep (PSQI score > 5). RESULTS Subjective and objective sleep durations were similar in this sample; average sleep times for the diary, morning questionnaire, and PSG were 340, 323, and 332 min, respectively. Average diary sleep time, subjective ratings of feeling rested, and PSG sleep efficiency were correlated significantly with PSQI score. Age was inversely correlated with PSG sleep time. Participants whose urine toxicology showed benzodiazapine use reported significantly longer sleep times on the morning questionnaire. CONCLUSIONS Objective sleep measures confirm subjective measures in MMT patients with disturbed sleep. The high prevalence of sleep complaints in this population likely reflects pathology rather than sleep misperception. Both objective and subjective measures are useful in research and clinical settings for assessing sleep in opioid-dependent patients.

Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). an update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

Effects of menopausal status on sleep in midlife women.

Disturbed sleep is a common complaint of midlife women often attributed to menopause, though few studies have examined direct effects of menopausal status on sleep. Our objective was to assess this issue in healthy midlife women. We examined sleep polysomnographically on 2 consecutive nights in 25 women (ages 45 - 56 yrs) without sleep complaints (13 pre-menopausal; 12 post-menopausal). Groups differed in Stage 1 % (lower in post-menopausal) and slow wave sleep latency (shorter in post-menopausal). Subjective sleep reports did not differ. Age correlated negatively with Stage 1 % and positively with Stage 4 %. These results indicate that menopausal status plays a minimal role in sleep quality and sleep stage distribution in healthy midlife women without sleep complaints.

Circadian Phase Shifts and Mood across the Perinatal Period in Women with a History of Major Depressive Disorder: A Preliminary Communication

BACKGROUND Perinatal changes in maternal sleep patterns may modify circadian phase. Our objectives were to (a) measure changes in circadian phase and phase angle between salivary dim light melatonin onset (DLMO) and sleep onset across the perinatal period; and (b) prospectively examine associations between circadian measures and depressed mood in women with a history of major depressive disorder (MDD). METHODS Twelve women (age±SD=26.9±5 years) who fulfilled DSM-IV criteria for history of MDD (but not in a mood episode at enrollment) were studied from third trimester of pregnancy through postpartum week 6. Participants completed sleep diaries, wore wrist actigraphs and light sensors, and had mood assessed with the Hamilton Depression Rating Scale (HAMD-17) during 3 separate weeks of the perinatal period; they gave saliva samples at 33 weeks gestation and 6 weeks postpartum to determine DLMO phase. RESULTS Nine women had DLMO phase shifts ≥30 min. On average±SD, new mothers phase delayed 42±80 min (range=163 min phase delay to 144 min phase advance). The time interval between average actigraphic sleep onset and DLMO was shorter at 6 weeks postpartum compared to 3rd trimester in 9 of 12 women, indicating that most new mothers were going to bed closer to the onset of endogenous melatonin secretion. Circadian measures were associated with depressed mood at postpartum weeks 2 and 6. LIMITATIONS These data are preliminary findings from a small sample and require replication. CONCLUSIONS We observed individual differences in magnitude and direction of circadian phase shifts and their timing relative to sleep across the perinatal period. These measures were correlated with postpartum depressive symptoms. These preliminary data indicate that changes in perinatal circadian rhythms may contribute to the development of postpartum mood disorders.

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American Academy of Sleep Medicine Clinical Practice Guideline.

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.