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Lancet (London, England) Jul 2022Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
METHODS
In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ.
FINDINGS
We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]).
INTERPRETATION
Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice.
FUNDING
UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adult; Benzodiazepines; Doxepin; Eszopiclone; Humans; Melatonin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Zolpidem
PubMed: 35843245
DOI: 10.1016/S0140-6736(22)00878-9 -
Sleep Medicine Reviews Dec 2022We conducted systematic reviews and meta-analyses to evaluate the efficacy of melatonin versus placebo or other hypnotic agents in improving sleep quality and quantity... (Meta-Analysis)
Meta-Analysis Review
We conducted systematic reviews and meta-analyses to evaluate the efficacy of melatonin versus placebo or other hypnotic agents in improving sleep quality and quantity in patients with chronic insomnia. A literature search on Ovid-MEDLINE, EMBASE, and the Cochrane Library was performed up to November 2020. Sleep onset latency, total sleep time, sleep efficiency, sleep quality and quality of life were examined as outcomes. We identified 24 randomized controlled trials of chronic insomnia including four studies of patients with comorbid insomnia. All studies were compared with placebo. Due to heterogeneity, we conducted subgroup analyses by age group. In non-comorbid insomnia, melatonin was only significantly effective in sleep onset latency and total sleep time in children and adolescents. In adults group, melatonin was not significantly effective in improving sleep onset latency, total sleep time, and sleep efficiency. In comorbid insomnia, melatonin significantly improved sleep onset latency in all age groups, but there was only one study in adults group. In conclusion, melatonin did not appear to be effective in adults but might be effective in children and adolescents with chronic insomnia for both comorbid insomnia and non-comorbid insomnia. Further studies are needed to establish the efficacy and safety of melatonin by age groups.
Topics: Adolescent; Child; Humans; Melatonin; Quality of Life; Sleep Initiation and Maintenance Disorders
PubMed: 36179487
DOI: 10.1016/j.smrv.2022.101692 -
Journal of Neurology Jan 2022The Present study was conducted to systematically review the effect of the melatonin on sleep quality. We summarized evidence from randomized clinical trials (RCTs) that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Present study was conducted to systematically review the effect of the melatonin on sleep quality. We summarized evidence from randomized clinical trials (RCTs) that investigated the effects of melatonin on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in adults with various diseases.
METHODS
The literature searches of English publications in MEDLINE and EMBASE databases were performed up June 2020. Results were summarized as mean differences (MD) with 95% confidence intervals (CI) using random effects model (DerSimonian-Laird method). Heterogeneity among studies was evaluated by the Cochrane Q test and I-squared (I2). To determine the predefined sources of heterogeneity, subgroup analysis was performed.
RESULTS
Of 2642 papers, 23 RCTs met inclusion criteria. Our results indicated that melatonin had significant effect on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) (WMD: - 1.24; 95% CI - 1.77, - 0.71, p = 0.000). There was significant heterogeneity between studies (I = 80.7%, p = 0.000). Subgroup analysis based on health status and kind of intervention were potential between-study heterogeneity. Subgroup analysis based on health status revealed melatonin intervention in subjects with Respiratory diseases (WMD: - 2.20; 95% CI - 2.97, - 1.44, p = 0.000), Metabolic disorders (WMD: - 2.74; 95% CI - 3.48, - 2.00, p = 0.000) and sleep disorders (WMD: - 0.67; 95% CI - 0.98, - 0.37, p = 0.000) has significant effect on sleep quality.
CONCLUSION
We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in adult. In adults with respiratory diseases, metabolic disorders, primary sleep disorders, not with mental disorders, neurodegenerative diseases and other diseases.
Topics: Adult; Dietary Supplements; Humans; Melatonin; Randomized Controlled Trials as Topic; Sleep Quality; Sleep Wake Disorders
PubMed: 33417003
DOI: 10.1007/s00415-020-10381-w -
Journal of the American College of... Dec 2022Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified.
BACKGROUND
Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified.
OBJECTIVES
The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes.
METHODS
This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events.
RESULTS
A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. β-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17).
CONCLUSIONS
Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Risk Factors; Heart Disease Risk Factors; Vitamin D; Folic Acid; Stroke
PubMed: 36480969
DOI: 10.1016/j.jacc.2022.09.048 -
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
General Hospital Psychiatry 2022We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium... (Review)
Review
OBJECTIVE
We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium symptoms among hospitalized adults.
METHODS
Searches of PubMed, Scopus, Embase, and Cochrane Library databases from inception to May 2021 were performed to identify studies investigating efficacy of pharmacologic agents for management of delirium.
RESULTS
Of 11,424 articles obtained from searches, a total of 33 articles (N = 3030 participants) of randomized or non-randomized trials, in which pharmacologic treatment was compared to active comparator, placebo, or no treatment, met all criteria and were included in this review. Medications used for management of delirium symptoms included antipsychotic medications (N = 27), alpha-2 agonists (N = 5), benzodiazepines (N = 2), antidepressants (n = 1), acetylcholinesterase inhibitors (N = 2), melatonin (N = 2), opioids (N = 1), and antiemetics (N = 2). Despite somewhat mixed findings and a relative lack of high-quality trials, it appears that antipsychotic medications (e.g., haloperidol, olanzapine, risperidone, or quetiapine) and dexmedetomidine have the potential to improve delirium outcomes.
CONCLUSIONS
Pharmacologic agents can reduce delirium symptoms (e.g., agitation) in some hospitalized patients. Additional double-blinded, randomized, placebo-controlled clinical trials are critically needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations (e.g., post-surgical patients, patients at the end-of-life, or in intensive care units).
Topics: Adult; Humans; Antipsychotic Agents; Delirium; Acetylcholinesterase; Haloperidol; Risperidone
PubMed: 36375344
DOI: 10.1016/j.genhosppsych.2022.10.010 -
Sleep Medicine Reviews Apr 2023Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We... (Meta-Analysis)
Meta-Analysis Review
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
Topics: Humans; Adult; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Sleep; Hypnotics and Sedatives; Wakefulness; Treatment Outcome
PubMed: 36701954
DOI: 10.1016/j.smrv.2023.101746 -
Journal of Psychiatric Research Jan 2021Melatonin, a pineal gland hormone is reported to have a protective effect against delirium. This systematic review and meta-analysis explores the effect of melatonin and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Melatonin, a pineal gland hormone is reported to have a protective effect against delirium. This systematic review and meta-analysis explores the effect of melatonin and melatonin receptor agonist, ramelteon on delirium prevention in adult hospitalized patients.
METHODS
Randomized Controlled trials of melatonin/ramelteon published up to May 7, 2020 were identified from MEDLINE, PREMEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled trials, PubMed, and Google Scholar. The primary outcome was delirium incidence. The secondary outcomes were sleep quality, sedation score, sedatives requirement, delirium duration, length of hospital stay, length of Intensive Care Unit (ICU) stay, mortality and adverse events. A meta-analysis with a random-effects models was performed. Estimates were presented as Risk Ratio (RR) or Mean Differences (MD) with 95% Confidence Interval (CI).
FINDINGS
Fourteen studies with 1712 participants were included. Melatonin/ramelteon significantly reduced delirium incidence (RR 0·61, 95% CI 0·42-0·89, p 0·009) with risk reduction of 49% in surgical patients and 34% in ICU patients. Non-significant reduction was found in medical patients. Melatonin/ramelteon were associated with improvement in sleep quality, increased sedation score and lower sedatives consumption. However, they did not reduce delirium duration, length of hospital stay, length of ICU stay and mortality. Hallucinations, nightmares and gastrointestinal disorders were prevalent in melatonin group.
INTERPRETATION
Melatonin/ramelteon are associated with reduction in delirium incidence in hospitalized patients. However, this effect seems confined to surgical and ICU patients. The optimum dosage and formulation of melatonin, and treatment duration remain uncleared and open to further studies with larger sample sizes.
Topics: Adult; Delirium; Humans; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Melatonin
PubMed: 33348252
DOI: 10.1016/j.jpsychires.2020.12.020 -
CNS Drugs Oct 2021Borderline personality disorder (BPD) is a debilitating psychiatric disorder that affects 0.4-3.9% of the population in Western countries. Currently, no medications have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Borderline personality disorder (BPD) is a debilitating psychiatric disorder that affects 0.4-3.9% of the population in Western countries. Currently, no medications have been approved by regulatory agencies for the treatment of BPD. Nevertheless, up to 96% of patients with BPD receive at least one psychotropic medication.
OBJECTIVES
The objective of this systematic review was to assess the general efficacy and the comparative effectiveness of different pharmacological treatments for BPD patients.
METHODS
We conducted systematic literature searches limited to English language in MEDLINE, EMBASE, the Cochrane Library, and PsycINFO up to April 6, 2021, and searched reference lists of pertinent articles and reviews. Inclusion criteria were (i) patients 13 years or older with a diagnosis of BPD, (ii) treatment with anticonvulsive medications, antidepressants, antipsychotic medications, benzodiazepines, melatonin, opioid agonists or antagonists, or sedative or hypnotic medications for at least 8 weeks, (iii) comparison with placebo or an eligible medication, (iv) assessment of health-relevant outcomes, (v) randomized or non-randomized trials or controlled observational studies. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. For meta-analyses, we used restricted maximum likelihood random effects models to estimate pooled effects.
RESULTS
Of 12,062 unique records, we included 21 randomized controlled trials (RCTs) with data on 1768 participants. Nineteen RCTs compared pharmacotherapies with placebo; two RCTs assessed active treatments head-to-head. Out of 87 medications in use in clinical practice, we found studies on just nine. Overall, the evidence indicates that the efficacy of pharmacotherapies for the treatment of BPD is limited. Second-generation antipsychotics, anticonvulsants, and antidepressants were not able to consistently reduce the severity of BPD. Low-certainty evidence indicates that anticonvulsants can improve specific symptoms associated with BPD such as anger, aggression, and affective lability but the evidence is mostly limited to single studies. Second-generation antipsychotics had little effect on the severity of specific BPD symptoms, but they improved general psychiatric symptoms in patients with BPD.
CONCLUSIONS
Despite the common use of pharmacotherapies for patients with BPD, the available evidence does not support the efficacy of pharmacotherapies alone to reduce the severity of BPD.
REGISTRATION
PROSPERO registration number, CRD42020194098.
Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Borderline Personality Disorder; Humans; Psychotropic Drugs; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34495494
DOI: 10.1007/s40263-021-00855-4 -
Postgraduate Medical Journal Apr 2022Different dietary supplements aimed at improving sleep quality are available on the market, but there has not been a comprehensive review to evaluate the efficacy of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Different dietary supplements aimed at improving sleep quality are available on the market, but there has not been a comprehensive review to evaluate the efficacy of these dietary supplements on subjective sleep quality. We aimed to summarise up-to-date research evidence and to identify the types of dietary supplement that improve subjective sleep quality.
METHODS
Multiple databases (Ovid Emcare, Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and APA PsycInfo) were used for searching papers published until August 2020. The changes in sleep quality indices, intervention duration and sample size were extracted from every paper. To analyse the effect of dietary supplements on sleep quality, a random effects model with mean difference (MD) and 95% CI was adopted. The heterogeneity across studies was measured by I statistics. The quality of included studies was evaluated by Cochrane's risk of bias tool.
RESULTS
Thirty-one randomised controlled trials of dietary supplements were included. Subjective sleep quality was significantly improved by supplementation of amino acids (MD -1.27, 95% CI -2.35 to -0.20; I=0%), melatonin (MD -1.21, 95% CI -2.17 to -0.24; I=79%) and vitamin D (MD -1.63, 95% CI -3.15 to -0.10; I=85%). Although not all studies provided adequate data for meta-analysis, we also discussed how magnesium, zinc, resveratrol and nitrate supplementation may improve sleep quality.
CONCLUSIONS
Amino acids, vitamin D and melatonin supplements were significantly beneficial to improve sleep quality. However, high heterogeneity and wide confidence levels were observed in vitamin D and melatonin. Further research on the effect of magnesium, zinc, resveratrol and nitrate supplementation on improving sleep quality is required.
Topics: Dietary Supplements; Humans; Sleep Quality; Vitamins
PubMed: 33441476
DOI: 10.1136/postgradmedj-2020-139319