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PloS One 2015We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.
METHODS
Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations through June 27, 2015. We performed a systematic review and meta-analysis of suvorexant trial efficacy and safety outcomes. The primary efficacy outcomes were either subjective total sleep time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary outcomes were other efficacy outcomes, discontinuation rate, and individual adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean difference (WMD) and 95% confidence intervals (CI) based on a random effects model were calculated.
RESULTS
The computerized literature database search initially yielded 48 results, from which 37 articles were excluded following a review of titles and abstracts and another eight review articles after full-text review. Thus, we identified 4 trials that included a total of 3,076 patients. Suvorexant was superior to placebo with regard to the two primary efficacy outcomes (sTST: WMD = -20.16, 95% CI = -25.01 to -15.30, 1889 patients, 3 trials, sTSO: WMD = -7.62, 95% CI = -11.03 to -4.21, 1889 patients, 3 trials) and was not different from placebo in trial discontinuations. Suvorexant caused a higher incidence than placebo of at least one side effects, abnormal dreams, somnolence, excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.
CONCLUSIONS
Our analysis of published trial results suggests that suvorexant is effective in treating primary insomnia and is well-tolerated.
Topics: Azepines; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles
PubMed: 26317363
DOI: 10.1371/journal.pone.0136910 -
Drugs & Aging Jun 2014Melatonin is a hormone that regulates circadian rhythm, and its levels decline with age. As melatonin levels decrease, older adults are prone to develop disorders... (Review)
Review
BACKGROUND
Melatonin is a hormone that regulates circadian rhythm, and its levels decline with age. As melatonin levels decrease, older adults are prone to develop disorders related to an altered circadian rhythm. The effective dose of melatonin supplementation in these disorders remains unclear.
OBJECTIVES
Our objective was to define the optimal dosage of exogenous melatonin administration in disorders related to altered melatonin levels in older adults aged 55 years and above by determining the dose-response effect of exogenous administered melatonin on endogenous levels.
METHODS
We conducted a systematic review through PubMed/MEDLINE and Embase, both from 1980 until November 2013. Included articles studied the effect of exogenous melatonin administration on endogenous melatonin levels in either serum, urine, or saliva in humans aged 55 years and above.
RESULTS
We included 16 articles, nine of which were randomized controlled trials (RCTs). The mean age varied from 55.3 to 77.6 years. Melatonin dosage varied from 0.1 mg to 50 mg/kg and was administered orally in all studies. Pre- and post-intervention levels revealed a significant elevation of the post-intervention melatonin levels in a dose-dependent fashion. The maximum concentrations measured in serum and urine were all elevated compared with placebo, and a higher elevation in older adults than in younger adults was demonstrated. Even though there were no differences between times to reach maximum concentration in serum and urine, melatonin levels with higher doses were maintained longer above a certain threshold than were lower doses.
CONCLUSION
In older adults, we advise the use of the lowest possible dose of immediate-release formulation melatonin to best mimic the normal physiological circadian rhythm of melatonin and to avoid prolonged, supra-physiological blood levels.
Topics: Administration, Oral; Aged; Aged, 80 and over; Circadian Rhythm; Dietary Supplements; Dose-Response Relationship, Drug; Humans; Melatonin; Middle Aged; Saliva; Sleep Initiation and Maintenance Disorders
PubMed: 24802882
DOI: 10.1007/s40266-014-0178-0 -
Sleep Medicine Apr 2014Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis assessed the efficacy and safety of ramelteon for the treatment of insomnia in adults. We included both published and unpublished data from randomized placebo-controlled trials evaluating the efficacy of ramelteon in adults with insomnia in the analysis. Our primary outcomes were sleep quality, subjective sleep latency (sSL), and subjective total sleep time (sTST). Secondary outcomes included latency to persistent sleep (LPS), total sleep time (TST), sleep efficiency (SE), proportion of rapid eye movement (REM) sleep, wakefulness after sleep onset (WASO), subjective WASO, number of nighttime awakenings (NAW), subjective NAW, and adverse events. Thirteen trials involving 5812 patients with insomnia or insomnia symptoms with a mean study duration of 38 days were pooled. Ramelteon was associated with reduced sSL (weighted mean difference [WMD], -4.30 min [95% confidence interval {CI}, -7.01 to -1.58]) and improved sleep quality (standardized mean differences, -0.074 [95% CI, -0.13 to -0.02]) but was not associated with increased sTST. Ramelteon also was associated with improvement in LPS, SE, and TST. The only significant adverse event was somnolence. Short-term use of ramelteon was associated with improvement in some sleep parameters in patients with insomnia, but its clinical impact is small. Long-term trials are needed before solid conclusions can be established.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Indenes; Male; Middle Aged; Randomized Controlled Trials as Topic; Receptors, Melatonin; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult
PubMed: 24656909
DOI: 10.1016/j.sleep.2013.11.788 -
Journal of Affective Disorders Feb 2022Acute effects of COVID-19 can be life-threatening. Alterations in mental health during the active infection have been documented, but the long-term consequences are less...
BACKGROUND
Acute effects of COVID-19 can be life-threatening. Alterations in mental health during the active infection have been documented, but the long-term consequences are less clear.
METHOD
A systematic review was undertaken to investigate the effect of COVID-19 infection on long-term mental health outcomes. Three databases [PubMed, Medline (Ovid) and Cochrane library] were searched between 1st October 2019 and 29th August 2021 with additional hand searching to identify all published studies reporting symptoms of generalised anxiety, depression, post-traumatic stress disorder (PTSD), or sleep disturbance in participants at least one month after COVID-19 infection. The prevalence and mean symptom score of each were assessed.
RESULTS
Eight hundred and eighty five studies were found, of which 33 were included in the review involving a total of 6743 participants. The studies' risk of bias were typically fair quality. The median study age of participants was 57.8 years (IQR 49.3-60.7), with 63.0% male (IQR 57.0%-73.0%). Participants typically experienced no or mild symptoms of long-term anxiety (GAD-7, STAI-S, HADS) and depression (PHQ-9, BDI, PHQ-2, HADS). Prevalence varied depending on the measurement tool. Sleep disturbances (primarily insomnia) were most commonly reported as mild. PTSD prevalence was similar to anxiety and depression.
CONCLUSION
The overall effect of the pandemic has been linked with worsening psychiatric symptoms. However, the long-term effect from direct COVID-19 infection has been associated with no or mild symptoms. Studies exhibited the long-term prevalence of anxiety, depression, PTSD, and sleep disturbances to be comparable to general population levels.
Topics: Anxiety; COVID-19; Depression; Female; Humans; Male; Mental Health; Middle Aged; Pandemics; SARS-CoV-2
PubMed: 34798148
DOI: 10.1016/j.jad.2021.11.031 -
Drug and Alcohol Dependence Dec 2017To determine the efficacy of behavioral and pharmacological interventions for insomnia among individuals with alcohol use disorder (AUD). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine the efficacy of behavioral and pharmacological interventions for insomnia among individuals with alcohol use disorder (AUD).
PROCEDURES
Comprehensive literature searches of psychological, medical, and educational databases were conducted through October 2016. Eligible studies evaluated the efficacy of an insomnia intervention, included a comparison condition, sampled individuals with AUD and either insomnia disorder or complaints of insomnia, assessed sleep-related outcomes, and provided relevant statistics to calculate between-group effect sizes. Effect sizes were estimated for sleep quality, days of alcohol abstinence, and symptoms of depression. Type of intervention (behavioral versus pharmacological) was tested as a moderator of intervention efficacy.
MAIN FINDINGS
Nine studies met eligibility criteria and were included in the final review and meta-analysis. Random-effects models indicated that intervention participants reported greater improvements in sleep quality (d+=0.62, 95% CI=0.28, 0.97) and symptoms of depression (d+=0.52, 95% CI=0.06, 0.98) than control participants. Participants reported significantly greater improvements in sleep quality in response to behavioral (d+=1.20, 95% CI=0.70, 1.70) as opposed to pharmacological (d+=0.43, 95% CI=0.19, 0.67) interventions. Behavioral (d+=0.74, 95% CI=0.31, 1.18) and pharmacological (d+=0.08, 95% CI=-0.64, 0.78) interventions did not have significantly different effects on depressive symptoms. Neither behavioral nor pharmacological interventions improved rates of alcohol abstinence.
CONCLUSIONS
Insomnia interventions improve sleep quality and reduce symptoms of depression among individuals with comorbid AUD. Given the methodological weaknesses of studies reviewed, additional research is needed to determine the efficacy of insomnia treatment in improving rates of alcohol relapse within this population.
Topics: Adult; Alcoholism; Behavior Therapy; Depression; Female; Humans; Male; Middle Aged; Sleep; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 29096290
DOI: 10.1016/j.drugalcdep.2017.09.029 -
Sleep Medicine Dec 2023Cognitive behavioral therapy for insomnia (CBT-I) as a first-line treatment may improve insomnia in pregnant women. The efficacy of the components, modalities, doses,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive behavioral therapy for insomnia (CBT-I) as a first-line treatment may improve insomnia in pregnant women. The efficacy of the components, modalities, doses, and effectiveness of CBT-I in pregnant women at follow-up remains unclear.
OBJECTIVES
To assess the effectiveness of CBT-I in pregnant women and identify effective intervention components, modalities, and doses.
DESIGN
Systematic review and meta-analysis.
METHODS
Six English databases (PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL) and four Chinese databases (CNKI, WanFang Data, SinoMed, and CQVIP) were searched from inception to 10 January 2023. Randomized controlled trials (RCTs) on CBT-I in pregnant women with outcomes of insomnia severity measured by Insomnia Severity Index (ISI) or sleep quality measured by Pittsburgh Sleep Quality Index (PSQI). Two reviewers independently completed records selection, data extraction, and study quality assessment. The fixed-effect or random-effect model was used for pooled analyses. Subgroup analyses were conducted based on different delivery types and intervention duration. The GRADE approach was used to evaluate the certainty of the evidence. Narrative analyses were used when meta-analysis was not appropriate. Mean differences with 95% CIs of insomnia severity and sleep quality scores were the main outcomes (greater scores indicating greater severity).
RESULTS
Nine RCTs (N = 978) meeting the inclusion criteria were included. These trials included individual- (n = 6) or group-based (n = 3) interventions, which were conducted via face-to-face (n = 5), digital (n = 3) or telephone and e-mail (n = 1) formats. Six studies stated intervention components specific to pregnant women. CBT-I improved insomnia severity (MD = -2.69, 95% CI: -3.41 to -1.96, P < 0.001, high quality evidence; MD = -3.69, 95% CI: -5.91 to -1.47, P = 0.001, moderate quality evidence) and sleep quality (MD = -2.85, 95% CI: -4.73 to -0.97, P = 0.003, moderate quality evidence; MD = -1.88, 95% CI: -2.89 to -0.88, P < 0.001, moderate quality evidence) immediately after intervention (<1-month) and at short-term (≥1 month to <6 months) follow-up, respectively. Two RCTs reported no effectiveness on insomnia severity at medium-term (≥6 months to<12 months) follow-up. Only 1 RCT showed reduced insomnia severity at long-term (≥12 months) follow-up. One RCT reported no effectiveness in sleep quality at medium-term follow-up and effectiveness at long-term follow-up was not reported.
CONCLUSIONS
Pregnant women may benefit from CBT-I to improve short-term insomnia, but long-term effectiveness is unclear. Rigorous RCTs with long-term follow-ups are warranted.
Topics: Female; Pregnancy; Humans; Pregnant Women; Sleep Initiation and Maintenance Disorders; Cognitive Behavioral Therapy; Sleep Quality
PubMed: 37952481
DOI: 10.1016/j.sleep.2023.11.002 -
International Journal of Clinical... Sep 2012As a melatonin receptor agonist, ramelteon has been approved in the United States as a treatment for insomnia. As a potential alternation, ramelteon should be further... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
As a melatonin receptor agonist, ramelteon has been approved in the United States as a treatment for insomnia. As a potential alternation, ramelteon should be further evaluated in different doses and populations. This systematic review with meta-analysis aims to determine the efficacy and safety of ramelteon in the treatment of chronic insomnia.
METHODS
We systematically searched and identified in Medline, Embase, PsycINFO and Cochrane Library until September 2011. We only included randomised controlled trials focused on ramelteon, vs. placebo, or any other treatment for patients with chronic insomnia. Data were extracted and evaluated by two independent investigators. If neither clinical nor statistical heterogeneity was found, we pooled results using a fixed-effect model.
RESULTS
Eight studies were selected to include from 175 identified references. There were significant improvements in all the outcomes (subjective and polysomnographic sleep latency, total sleep time and latency to REM), except for the percentage of REM. By subgroup analysis, subjective sleep latency was reduced only in the patients of 18-64 years old, without in the patients over 65 years old. For the safety, ramelteon was not associated with higher risk ratio of any frequent adverse events comparing with control.
CONCLUSION
The efficacy and safety of ramelteon are promising for the chronic insomnia patients. More researches are required for robust conclusions, particularly well-designed; double-blind randomised controlled trials with higher doses of ramelteon (32 or 64 mg) for the older population comparing with other sedative hypnotics.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Humans; Hypnotics and Sedatives; Indenes; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Young Adult
PubMed: 22897464
DOI: 10.1111/j.1742-1241.2012.02987.x -
The Cochrane Database of Systematic... Oct 2018Insomnia is a major public health issue affecting between 6% to 10% of the adult population in Western countries. Eszopiclone is a hypnotic drug belonging to a newer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insomnia is a major public health issue affecting between 6% to 10% of the adult population in Western countries. Eszopiclone is a hypnotic drug belonging to a newer group of hypnotic agents, known as new generation hypnotics, which was marketed as being just as effective as benzodiazepines for this condition, while being safer and having a lower risk for abuse and dependence. It is the aim of the review to integrate evidence from randomised controlled trials and to draw conclusions on eszopiclone's efficacy and safety profile, while taking methodological features and bias risks into consideration.
OBJECTIVES
To assess the efficacy and safety of eszopiclone for the treatment of insomnia compared to placebo or active control.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, Embase, PsycINFO, PSYNDEX and registry databases (WHO trials portal, ClinicalTrials.gov) with results incorporated from searches to 10 February 2016. To identify trials not registered in electronic databases, we contacted key informants and searched reference lists of identified studies. We ran an update search (21 February 2018) and have placed studies of interest in awaiting classification/ongoing studies. These will be incorporated into the next version of the review, as appropriate.
SELECTION CRITERIA
Parallel group randomised controlled trials (RCTs) comparing eszopiclone with either placebo or active control were included in the review. Participants were adults with insomnia, as diagnosed with a standardised diagnostic system, including primary insomnia and comorbid insomnia.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted outcome data; one reviewer assessed trial quality and the second author cross-checked it.
MAIN RESULTS
A total of 14 RCTs, with 4732 participants, were included in this review covering short-term (≤ 4 weeks; 6 studies), medium-term (> 4 weeks ≤ 6 months; 6 studies) and long-term treatment (> 6 months; 2 studies) with eszopiclone. Most RCTs included in the review included participants aged between 18 and 64 years, three RCTs only included elderly participants (64 to 85 years) and one RCT included participants with a broader age range (35 to 85 years). Seven studies considered primary insomnia; the remaining studies considered secondary insomnia comorbid with depression (2), generalised anxiety (1), back pain (1), Parkinson's disease (1), rheumatoid arthritis (1) and menopausal transition (1).Meta-analytic integrations of participant-reported data on sleep efficacy outcomes demonstrated better results for eszopiclone compared to placebo: a 12-minute decrease of sleep onset latency (mean difference (MD) -11.94 min, 95% confidence interval (CI) -16.03 to -7.86; 9 studies, 2890 participants, moderate quality evidence), a 17-minute decrease of wake time after sleep onset (MD -17.02 min, 95% CI -24.89 to -9.15; 8 studies, 2295 participants, moderate quality evidence) and a 28-minute increase of total sleep time (MD 27.70 min, 95% CI 20.30 to 35.09; 10 studies, 2965 participants, moderate quality evidence). There were no significant changes from baseline to the first three nights after drug discontinuation for sleep onset latency (MD 17.00 min, 95% CI -4.29 to 38.29; 1 study, 291 participants, low quality evidence) and wake time after sleep onset (MD -6.71 min, 95% CI -21.25 to 7.83; 1 study, 291 participants, low quality evidence). Adverse events during treatment that were documented more frequently under eszopiclone compared to placebo included unpleasant taste (risk difference (RD) 0.18, 95% CI 0.14 to 0.21; 9 studies, 3787 participants), dry mouth (RD 0.04, 95% CI 0.02 to 0.06; 6 studies, 2802 participants), somnolence (RD 0.04, 95% CI 0.02 to 0.06; 8 studies, 3532 participants) and dizziness (RD 0.03, 95% CI 0.01 to 0.05; 7 studies, 2933 participants). According to the GRADE criteria, evidence was rated as being of moderate quality for sleep efficacy outcomes and adverse events and of low quality for rebound effects and next-day functioning.
AUTHORS' CONCLUSIONS
Eszopiclone appears to be an efficient drug with moderate effects on sleep onset and maintenance. There was no or little evidence of harm if taken as recommended. However, as certain patient subgroups were underrepresented in RCTs included in the review, findings might not have displayed the entire spectrum of possible adverse events. Further, increased caution is required in elderly individuals with cognitive and motor impairments and individuals who are at increased risk of using eszopiclone in a non-recommended way.
Topics: Adult; Aged; Aged, 80 and over; Eszopiclone; Humans; Hypnotics and Sedatives; Middle Aged; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome
PubMed: 30303519
DOI: 10.1002/14651858.CD010703.pub2 -
Sleep Medicine Reviews Feb 2024Insomnia disorder signifies a major public health concern. The development of neuroimaging techniques has permitted to investigate brain mechanisms at a structural and... (Review)
Review
Insomnia disorder signifies a major public health concern. The development of neuroimaging techniques has permitted to investigate brain mechanisms at a structural and functional level. The present systematic review aims at shedding light on functional, structural, and metabolic substrates of insomnia disorder by integrating the available published neuroimaging data. The databases PubMed, PsycARTICLES, PsycINFO, CINAHL and Web of Science were searched for case-control studies comparing neuroimaging data from insomnia patients and healthy controls. 85 articles were judged as eligible. For every observed finding of each study, the effect size was calculated from standardised mean differences, statistic parameters and figures, showing a marked heterogeneity that precluded a comprehensive quantitative analysis. From a qualitative point of view, considering the findings of significant group differences in the reported regions across the articles, this review highlights the major involvement of the anterior cingulate cortex, thalamus, insula, precuneus and middle frontal gyrus, thus supporting some central themes in the debate on the neurobiology of and offering interesting insights into the psychophysiology of sleep in this disorder.
Topics: Humans; Brain; Gyrus Cinguli; Neuroimaging; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 38056381
DOI: 10.1016/j.smrv.2023.101878 -
Sleep Medicine Jan 2021Repetitive transcranial magnetic stimulation (rTMS) might be a promising technique in treating insomnia. A comprehensive meta-analysis of the available literature is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) might be a promising technique in treating insomnia. A comprehensive meta-analysis of the available literature is conducted to offer evidence.
OBJECTIVE
To evaluate the efficacy and safety of rTMS for insomnia, either as monotherapy or as a complementary strategy.
METHODS
CENTRAL, PubMed, EMBASE, PsycINFO, CINAHL, PEDro, CBM, CNKI, WANFANG, and VIP were searched from earliest record to August 2019. Randomized control trials (RCTs) published in English and Chinese examining effects of rTMS on patients with insomnia were included. Two authors independently completed the article selection, data extraction and rating. Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of the included studies. The RevMan software was used for meta-analysis. The quality of the evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
A total of 36 trials from 28 eligible studies were included, involving a total of 2357 adult participants (mean age, 48.80 years; 45.33% males). Compared with sham rTMS, rTMS was associated with improved PSQI total score (SMD -2.31, 95% CI -2.95 to -1.66; Z = 7.01, P < 0.00001) and scores of seven subscales. Compared to other treatment, rTMS as an adjunct to other treatment was associated with improved PSQI total score (SMD -1.44, 95% CI -2.00 to -0.88; Z = 5.01, P < 0.00001), and may have effects on scores of seven subscales. Compared with other treatment, rTMS was associated with improved Pittsburgh sleep quality index (PSQI) total score (SMD -0.63, 95% CI -1.22 to -0.04; Z = 2.08, P = 0.04), and may have a better score in sleep latency, sleep disturbance and hypnotic using of seven subscales. In the three pair of comparisons, the results for polysomnography (PSG) outcomes were varied. In general, rTMS may improve sleep quality through increasing slow wave and rapid eye movement (REM) sleep. The rTMS group was more prone to headache than the sham or blank control group (RR 1.71, 95% CI 1.03 to 2.85; Z = 2.07, P = 0.04). No severe adverse events were reported. Reporting biases and low and very low grade of some evidences should be considered when interpreting the results of this meta-analysis.
CONCLUSIONS
Our findings indicate that rTMS may be a safe and effective option for insomnia. Further international, multicenter, high-quality RCTs with more objective, quality of life related and follow-up assessments are needed.
Topics: Adult; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Quality of Life; Sleep Initiation and Maintenance Disorders; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 32830052
DOI: 10.1016/j.sleep.2020.05.020