Sleep Initiation and Maintenance Disorders: Kripke DF

Kripke DF. · No affiliation provided · Sleep Med. · Pubmed #19269891 No free full text.

This publication has no abstract.

Kripke DF. · Department of Psychiatry, University of California, San Diego and The Scripps Clinic Sleep Center, La Jolla, California 92093-0667, USA. · J Sleep Res. · Pubmed #18844818 No free full text.

Abstract: Fifteen epidemiologic studies have associated hypnotic drugs with excess mortality, especially excess cancer deaths. Until recently, insufficient controlled trials were available to demonstrate whether hypnotics actually cause any cancers. The US Food and Drug Administration (FDA) Approval History and Documents were accessed for zaleplon, eszopiclone and ramelteon. Since zolpidem was used as a comparison drug in zaleplon trials, some zolpidem data were also available. Incident cancers occurring during randomized hypnotics administration or placebo administration were tabulated. Combining controlled trials for the four drugs, there were 6190 participants given hypnotics and 2535 given placebo in parallel. There were eight mentions of incident non-melanoma skin cancers among participants receiving hypnotics but no comparable mentions of cancers among those receiving placebo (P = 0.064, one-tailed). There were also four mentions of incident tumors of uncertain malignancy among those receiving hypnotics but none among those receiving placebo, so combining uncertain and definite malignancies yielded a more significant contrast (P = 0.016). FDA files revealed that all four of the new hypnotics were associated with cancers in rodents. Three had been shown to be clastogenic. Together with the epidemiologic data and laboratory studies, the available evidence signals that new hypnotics may increase cancer risk. Due to limitations in available data, confirmatory research is needed.

Kripke DF. · The Scripps Clinic Sleep Center, 10666 North Torrey Pines Road, La Jolla, California 92037, USA. · BMC Psychiatry. · Pubmed #17711589 links to  free full text

Abstract: BACKGROUND: Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. METHODS: The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. RESULTS: Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p < 0.002). CONCLUSION: Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.

Levine DW, Kripke DF, Kaplan RM, Lewis MA, Naughton MJ, Bowen DJ, Shumaker SA. · Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. · Psychol Assess. · Pubmed #12847774 No free full text.

Abstract: The reliability and construct validity of the 5-item Women's Health Initiative Insomnia Rating Scale (WHIIRS) were evaluated in 2 studies. In Study 1, using a sample of 66,269 postmenopausal women, validity of the WHIIRS was assessed by examining its relationship to other measures known to be related to sleep quality. Reliability of the WHIIRS was estimated using a resampling approach; the mean alpha coefficient was .78. Test-retest reliability coefficients were .96 for same-day administration and .66 after a year or more. Correlations of the WHIIRS with the other measures were in the predicted directions. Study 2 used a sample of 459 women and compared the WHIIRS with objective indicators of sleep quality. Results showed that differences in the objective indicators could be detected by the WHIIRS. Findings suggest that a between-group mean difference of approximately 0.50 of a standard deviation on the WHIIRS may be clinically meaningful.

Levine DW, Kaplan RM, Kripke DF, Bowen DJ, Naughton MJ, Shumaker SA. · Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. · Psychol Assess. · Pubmed #12847773 No free full text.

Abstract: As part of the Women's Health Initiative Study, the 5-item Women's Health Initiative Insomnia Rating Scale (WHIIRS) was developed. This article summarizes the development of the scale through the use of responses from 66,269 postmenopausal women (mean age = 62.07 years, SD = 7.41 years). All women completed a 10-item questionnaire concerning sleep. A novel resampling technique was introduced as part of the data analysis. Principal-axes factor analysis without iteration and rotation to a varimax solution was conducted for 120,000 random samples of 1,000 women each. Use of this strategy led to the development of a scale with a highly stable factor structure. Structural equation modeling revealed no major differences in factor structure across age and race-ethnic groups. WHIIRS norms for race-ethnicity and age subgroups are detailed.

Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR. · Department of Psychiatry 0667, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0667, USA. · Arch Gen Psychiatry. · Pubmed #11825133 links to  free full text

Abstract: BACKGROUND: Patients often complain about insufficient sleep or chronic insomnia in the belief that they need 8 hours of sleep. Treatment strategies may be guided by what sleep durations predict optimal survival and whether insomnia might signal mortality risks. METHODS: In 1982, the Cancer Prevention Study II of the American Cancer Society asked participants about their sleep duration and frequency of insomnia. Cox proportional hazards survival models were computed to determine whether sleep duration or frequency of insomnia was associated with excess mortality up to 1988, controlling simultaneously for demographics, habits, health factors, and use of various medications. RESULTS: Participants were more than 1.1 million men and women from 30 to 102 years of age. The best survival was found among those who slept 7 hours per night. Participants who reported sleeping 8 hours or more experienced significantly increased mortality hazard, as did those who slept 6 hours or less. The increased risk exceeded 15% for those reporting more than 8.5 hours sleep or less than 3.5 or 4.5 hours. In contrast, reports of "insomnia" were not associated with excess mortality hazard. As previously described, prescription sleeping pill use was associated with significantly increased mortality after control for reported sleep durations and insomnia. CONCLUSIONS: Patients can be reassured that short sleep and insomnia seem associated with little risk distinct from comorbidities. Slight risks associated with 8 or more hours of sleep and sleeping pill use need further study. Causality is unproven.

Youngstedt SD, Kripke DF, Elliott JA, Klauber MR. · Department of Psychiatry, Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA 92093-0667, USA. · J Pineal Res. · Pubmed #11589762 No free full text.

Abstract: This study examined the circadian phase adjustment of symptomatic elders ages 60-79 years in comparison with that of young, healthy adults ages 20-40 years. Seventy-two elders with complaints of insomnia or depression, and 30 young, healthy adults were assessed for 5-7 days at home. Sleep and illumination were recorded with Actillume wrist monitors and sleep diaries. Urine was collected over two 24-hr periods and assayed for 6-sulphatoxymelatonin (6-smt). The volunteers were then observed continuously for 5 nights and 4 days in the laboratory. In the laboratory, sleep periods were fixed at 8 hr with polysomnographic assessment of sleep, apnea-hypopnea, and nocturnal myoclonus. Circadian dispersion, defined as the mean variation of 6-smt acrophase from the median age-specific acrophase, was significantly greater in the older vs. young adults. Likewise, circadian malsynchronization, defined as the absolute number of hours (advance or delay) between the 6-smt acrophase and the middle of the sleep period, was significantly greater in the older vs. young volunteers. For the older volunteers, multiple regressions were calculated associating sleep with potential correlates of sleep disturbance. Nocturnal myoclonus and circadian malsynchronization were more strongly associated with sleep impairment than other factors (e.g., sleep apnea, depression). These observations suggest that circadian malsynchronization might be a common and significant cause of disturbed sleep among adults over age 60.

Kripke DF. · No affiliation provided · Sleep Med Rev. · Pubmed #12628218 No free full text.

This publication has no abstract.