-
JAMA Network Open Dec 2023Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted.
OBJECTIVES
To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted.
DESIGN, SETTING, AND PARTICIPANTS
In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023.
INTERVENTIONS
Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone).
MAIN OUTCOMES AND MEASURES
Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components.
RESULTS
Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, -3.5 [95% CI, -4.7 to -2.3] vs -4.3 [95% CI, -5.7 to -2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, -4.7 [95% CI, -7.3 to -2.2] vs -5.2 [95% CI, -7.9 to -2.5]), functional impairments (Work and Social Adjustment Scale mean score change, -5.0 [95% CI, -6.7 to -3.3] vs -5.1 [95% CI, -7.2 to -2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, -4.1 [95% CI, -5.8 to -2.4] vs -1.2 [95% CI, -3.0 to 0.5]; P = .02; Cohen d = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, -3.8 [95% CI, -7.1 to -0.4]; zolpidem plus trazodone, -3.7 [95% CI, -6.3 to -1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, -3.7 [95% CI, -6.4 to -1.0]; zolpidem plus trazodone, -3.3 [95% CI, -5.9 to -0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01651442.
Topics: Adult; Female; Humans; Middle Aged; Behavior Therapy; Fatigue; Sleep Initiation and Maintenance Disorders; Trazodone; Zolpidem; Male
PubMed: 38153735
DOI: 10.1001/jamanetworkopen.2023.49638 -
Menopause (New York, N.Y.) Aug 2023Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2).
METHODS
This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949). During treatment period 1 (TP1), participants received PBO or LEM 5 mg (LEM5) or 10 mg (LEM10). During TP2 (second 6 mo), LEM participants continued their assigned dose; PBO participants were rerandomized to LEM5 or LEM10. Assessments included patient-reported sleep- and fatigue-related measures and treatment-emergent adverse events.
RESULTS
The midlife female subgroup comprised 280 of 949 participants (TP1: PBO, n = 90 of 318 [28.3%]; LEM5, n = 82 of 316 [25.9%]; LEM10, n = 108 of 315 [34.3%]). At 6 months, median changes from baseline in subjective sleep-onset latency (in minutes) were -17.9, -20.7, and - 30.4 for PBO, LEM5, and LEM10 (vs PBO: LEM5, P = not significant; LEM10, P = 0.0310). At 6 months, mean changes from baseline in subjective wake after sleep onset (in minutes) were -37.0 (59.6), -50.1 (74.5), and -54.5 (65.4) for PBO, LEM5, and LEM10 (vs PBO: LEM5 and LEM10, P = not significant), with benefits sustained through 12 months. Greater decreases from baseline (improvement) in Insomnia Severity Index total score and Fatigue Severity Scale total score were seen with LEM versus PBO at 6 months; benefits continued through 12 months. Most treatment-emergent adverse events were mild to moderate in severity.
CONCLUSIONS
Consistent with the total population, subjective sleep parameters improved, and improvement was sustained over time in midlife women. LEM was well tolerated, suggesting that LEM may be a potential treatment option for midlife women with insomnia.
Topics: Adult; Female; Humans; Middle Aged; Double-Blind Method; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Menopause; Perimenopause
PubMed: 37339396
DOI: 10.1097/GME.0000000000002209 -
Journal of Gerontological Nursing Nov 2022The purpose of the current study was to describe the experiences of middle-aged and older adults with chronic insomnia. A descriptive qualitative study design was used,...
The purpose of the current study was to describe the experiences of middle-aged and older adults with chronic insomnia. A descriptive qualitative study design was used, and semi-structured interviews were conducted with 17 participants from two primary clinic health centers in northern Taiwan. Mean age of participants was 64.3 years, most (58.8%) participants were middle aged (aged 40 to 64 years), and mean duration of insomnia was 5.6 years. Three themes emerged: , , and . Participants believed chronic insomnia contributed to an accumulation of anxiety and negative emotions, resulting in psychological burden. For participants with insomnia, because of their negative impressions of hypnotics, they usually sought alternative therapies to improve sleep. Health care providers should endeavor to understand the needs of individuals with insomnia and provide them with sleep hygiene knowledge and assistance in safe sleep practices. [(11), 21-28.].
Topics: Humans; Middle Aged; Aged; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives; Sleep; Qualitative Research; Asian People
PubMed: 36286506
DOI: 10.3928/00989134-20221003-06 -
Cancer Medicine Jul 2022There is a growing cohort of head and neck cancer (HNC) patients affected by late- and long-term posttreatment side effects. Our study evaluates the relationship between...
BACKGROUND
There is a growing cohort of head and neck cancer (HNC) patients affected by late- and long-term posttreatment side effects. Our study evaluates the relationship between the demographics, clinical characteristics, and posttreatment symptom burden with the subjective sense of flourishing among HNC survivors.
METHODS
A cross-sectional, single-center study of adult survivors of squamous cell cancer of the oral cavity, oropharynx, and larynx/hypopharynx who completed the Secure Flourishing Index (SFI) and patient-reported outcomes related to depression, anxiety, swallowing dysfunction, neck disability, and insomnia between November 2020 and April 2021.
RESULTS
A total of 100, predominantly male (86%), survivors with an average age of 63.0 ± 9.6 were included in the study. Univariable analysis showed a significant association between higher flourishing scores and advanced age (95% CI: [0.011, 0.84], p = 0.0441), normal diet (95% CI: [5.79, 31.18], p = 0.0149), employment (95% CI: [1.24, 17.20], p = 0.0239), higher income (95% CI: [7.30, 27.72], p = 0.0248), and decreased reported difficulty paying for needs (95% CI: [-33.46, -18.88], p < 0.001). Flourishing was inversely associated with higher symptoms of depression (95% CI: [-2.23, -1.15], p < 0.001), anxiety (95% CI: [-1.92,-0.86], p < 0.001), swallowing dysfunction (95% CI: [-0.77, -0.26], p < 0.001), neck disability (95% CI: [-1.05, -0.35], p < 0.001), and insomnia (95% CI: [-1.12, -0.22], p = 0.004) in the multivariable analysis.
CONCLUSIONS
Common late- and long-term side effects of HNC treatment and financial hardship are associated with lower levels of flourishing or a more negative perception of life after treatment. Results highlight the importance of symptom burden for survivors' overall evaluation of their quality of life.
Topics: Adult; Aged; Cancer Survivors; Cross-Sectional Studies; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Quality of Life; Sleep Initiation and Maintenance Disorders; Survivors
PubMed: 35277936
DOI: 10.1002/cam4.4636 -
Alzheimer's & Dementia : the Journal of... Mar 2022We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with...
INTRODUCTION
We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk.
METHODS
We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.65 ± 8.7 years, 50.9% male). Additionally, we explored insomnia symptoms combined with self-reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status.
RESULTS
More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers.
DISCUSSION
Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration.
Topics: Aged; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Cognition; Female; Genotype; Humans; Male; Middle Aged; Neuropsychological Tests; Sleep Initiation and Maintenance Disorders
PubMed: 34310026
DOI: 10.1002/alz.12405 -
PloS One 2022We determined the association between Toxoplasma gondii (T. gondii) infection and insomnia. Through an age-and gender-matched case-control study, 577 people with...
We determined the association between Toxoplasma gondii (T. gondii) infection and insomnia. Through an age-and gender-matched case-control study, 577 people with insomnia (cases) and 577 people without insomnia (controls) were tested for anti-T. gondii IgG and IgM antibodies using commercially available enzyme-immunoassays. Anti-T. gondii IgG antibodies were found in 71 (12.3%) of 577 individuals with insomnia and in 46 (8.0%) of 577 controls (OR = 1.62; 95% CI: 1.09-2.39; P = 0.01). Men with insomnia had a higher (16/73: 21.9%) seroprevalence of T. gondii infection than men without insomnia (5/73: 6.8%) (OR: 3.81; 95% CI: 1.31-11.06; P = 0.009). The rate of high (>150 IU/ml) anti-T. gondii IgG antibody levels in cases was higher than the one in controls (OR = 2.21; 95% CI: 1.13-4.31; P = 0.01). Men with insomnia had a higher (8/73: 11.0%) rate of high anti-T. gondii IgG antibody levels than men without insomnia (0/73: 0.0%) (P = 0.006). The rate of high anti-T. gondii IgG antibody levels in cases >50 years old (11/180: 6.1%) was higher than that (3/180: 1.7%) in controls of the same age group (OR: 3.84; 95% CI: 1.05-14.00; P = 0.05). No difference in the rate of IgM seropositivity between cases and controls was found (OR = 1.33; 95% CI: 0.57-3.11; P = 0.50). Results of this seroepidemiology study suggest that infection with T. gondii is associated with insomnia. Men older than 50 years with T. gondii exposure might be prone to insomnia. Further research to confirm the association between seropositivity and serointensity to T. gondii and insomnia is needed.
Topics: Antibodies, Protozoan; Case-Control Studies; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Risk Factors; Seroepidemiologic Studies; Sleep Initiation and Maintenance Disorders; Toxoplasma; Toxoplasmosis
PubMed: 35679264
DOI: 10.1371/journal.pone.0266214 -
CNS Neuroscience & Therapeutics Aug 2023The purpose of this study was to investigate the association between spontaneous regional activity and brain functional connectivity, which maybe can distinguish...
AIMS
The purpose of this study was to investigate the association between spontaneous regional activity and brain functional connectivity, which maybe can distinguish insomnia while being responsive to repetitive transcranial magnetic stimulation (rTMS) treatment effects in insomnia patients.
METHODS
Using resting-state functional magnetic resonance imaging data from 38 chronic insomnia patients and 36 healthy volunteers, we compared the amplitude of low-frequency fluctuations (ALFF) between the two groups. Of all the patients with insomnia, 20 received rTMS for 4 weeks, while 18 patients received a 4-week pseudo-stimulation intervention. Seed-based resting-state functional connectivity (RSFC) analysis was conducted from regions with significantly different ALFF values, and the association between RSFC value and Pittsburgh Sleep Quality Index score was determined.
RESULTS
Our results revealed that insomnia patients presented a significantly higher ALFF value in the posterior cingulate cortex (PCC), whereas a significantly lower ALFF value was observed in the superior parietal lobule (SPL). Moreover, significantly reduced RSFC was detected from both PCC to prefrontal cortex connections, as well as from left SPL to frontal pole connections. In addition, RSFC from frontal pole to left SPL negatively predicted sleep quality (PSQI) and treatment response in patients' group.
CONCLUSION
Our findings suggest that disrupted frontoparietal network connectivity may be a biomarker for insomnia in middle-aged adults, reinforcing the potential of rTMS targeting the frontal lobes. Monitoring pretreatment RSFC could offer greater insight into how rTMS treatments are responded to by insomniacs.
Topics: Adult; Middle Aged; Humans; Sleep Initiation and Maintenance Disorders; Magnetic Resonance Imaging; Brain; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 36942498
DOI: 10.1111/cns.14183 -
Sleep Medicine Jan 2023We used baseline polysomnography (PSG) data obtained during the clinical program development for suvorexant to compare the PSG profiles of people with Alzheimer's...
BACKGROUND
We used baseline polysomnography (PSG) data obtained during the clinical program development for suvorexant to compare the PSG profiles of people with Alzheimer's disease and insomnia (ADI) versus age-matched elderly individuals with insomnia (EI).
METHODS
Sleep laboratory baseline PSG data from participants age 55-80 years from 2 trials in people with insomnia and a trial in people with ADI were included. ADI participants had dementia of mild-to-moderate severity. Diagnostic criteria for insomnia, exclusion for other sleep problems, PSG recording procedures, and endpoint derivations were similar across the trials. All participants underwent a night of in-laboratory PSG prior to the baseline night to allow for screening/adaptation. Participants in the EI and ADI groups were compared with regard to sleep architecture, sleep micro-structure, and quantitative EEG power spectral endpoints. The analysis was performed on a post hoc basis using propensity score matching to compare sleep parameters separately in women and men while accounting for age group and total sleep time.
RESULTS
A total of 837 EI and 239 ADI participants were included, with the majority in each population (∼65%) being women. Compared to EI, those with ADI had a lower percentage of time spent in slow wave sleep (and a corresponding higher percentage of time spent in the lighter N1 sleep), a lower number of spindles per minute of N2 sleep, and lower absolute EEG power during NREM sleep, particularly in the lower-frequency bands. Trends for lower REM sleep percentage in ADI did not reach statistical significance.
CONCLUSIONS
Our findings in this large data set, in which the influence of sleep problems was effectively subtracted out (since both groups had insomnia), provide strong confirmatory support of results from previous smaller studies in indicating that AD of mild-to-moderate severity is associated with less slow wave sleep, spindles, and lower-frequency EEG power.
TRIAL REGISTRATION
ClinicalTrials.gov, numbers NCT01097616, NCT01097629, NCT02750306.
Topics: Male; Humans; Female; Aged; Middle Aged; Aged, 80 and over; Sleep Initiation and Maintenance Disorders; Polysomnography; Alzheimer Disease; Sleep; Sleep, REM
PubMed: 36529106
DOI: 10.1016/j.sleep.2022.11.027 -
International Journal of Environmental... Jan 2021There is conflicting evidence regarding the association between insomnia and the onset of mild cognitive impairment (MCI) or dementia. This study aimed to evaluate if...
There is conflicting evidence regarding the association between insomnia and the onset of mild cognitive impairment (MCI) or dementia. This study aimed to evaluate if time-varying insomnia is associated with the development of MCI and dementia. Data from the Health and Retirement Study ( = 13,833) from 2002 to 2014 were used (59.4% female). The Brief Insomnia Questionnaire was used to identify insomnia symptoms which were compiled in an insomnia severity index, ranging from 0 to 4. In analysis, participants' symptoms could vary from wave-to-wave. Dementia was defined using results from the Health and Retirement Study (HRS) global cognitive assessment tool. Respondents were classified as either having dementia, MCI, or being cognitively healthy. Cox proportional hazards models with time-dependent exposure using the counting process (start-stop time) were used for analysis. For each one-unit increase in the insomnia symptom index, there was a 5-percent greater hazard of MCI (HR = 1.05; 95% CI: 1.04-1.06) and dementia (HR = 1.05; 95% CI: 1.03-1.05), after fully adjusting. Using a nationally representative sample of adults age 51 and older, this study found that time-varying insomnia symptoms are associated with risk of MCI and dementia. This highlights the importance of identifying sleep disturbances and their change over time as potentially important risk factors for MCI and dementia.
Topics: Aged; Cognitive Dysfunction; Dementia; Female; Humans; Incidence; Male; Middle Aged; Neuropsychological Tests; Risk Factors; Sleep Initiation and Maintenance Disorders; United States
PubMed: 33466468
DOI: 10.3390/ijerph18010351 -
BMC Psychiatry Sep 2022The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as...
BACKGROUND
The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers.
METHODS
We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment).
RESULTS
Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ (163) = 327.423, (p < 0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers.
CONCLUSIONS
This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients.
Topics: Adult; Aged; Arousal; Female; Humans; Japan; Male; Middle Aged; Psychometrics; Reproducibility of Results; Sleep Initiation and Maintenance Disorders
PubMed: 36123639
DOI: 10.1186/s12888-022-04243-0