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Frontiers in Psychiatry 2021We conducted a meta-analysis to assess the effects of different regular exercise (lasting at least 2 months on a regular basis) on self-reported and physiological sleep...
We conducted a meta-analysis to assess the effects of different regular exercise (lasting at least 2 months on a regular basis) on self-reported and physiological sleep quality in adults. Varied exercise interventions contained traditional physical exercise (e.g., walking, cycling) and mind-body exercise characterized by gentle exercise with coordination of the body (e.g., yoga). Procedures followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Systematical searches were conducted in three electronic databases (PubMed, Embase, and Web of Science) for relevant research that involved adult participants without pathological diseases receiving exercise intervention. The search strategy was based on the population, intervention, comparison, and outcome study design (PICOS) framework. The self-reported outcomes included varied rating scales of Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS). Subgroup meta-analyses of PSQI scores were conducted based on type of exercise, duration of intervention, and participants' age and gender. The physiological outcomes were measured by Actigraph. All meta-analyses were performed in a fixed or random statistic model using Revman software. Twenty-two randomized controlled trials were included in the analysis. The overall analysis on subjective outcomes suggests that exercise interventions significantly improved sleep quality in adults compared with control interventions with lower PSQI (MD -2.19; 95% CI -2.96 to -1.41), ISI (MD -1.52; 95% CI -2.63 to -0.41), and ESS (MD -2.55; 95% CI -3.32 to -1.78) scores. Subgroup analyses of PSQI scores showed both physical and mind-body exercise interventions resulted in improvements of subjective sleep to the same extent. Interestingly, short-term interventions (≤3 months) had a significantly greater reduction in sleep disturbance vs. long-term interventions (>3 months). Regarding physiological sleep, few significant effects were found in various sleep parameters except the increased sleep efficiency in the exercise group vs. control group. Results of this systematic review suggest that regular physical as well as mind-body exercise primarily improved subjective sleep quality rather than physiological sleep quality in adults. Specifically, self-reported sleep quality, insomnia severity, and daytime sleepiness could be improved or ameliorated with treatment of exercise, respectively, evaluated by PSQI, ISI, and ESS sleep rating scales.
PubMed: 34163383
DOI: 10.3389/fpsyt.2021.664499 -
The Cochrane Database of Systematic... Oct 2017Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'.
OBJECTIVES
To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults.
METHODS
We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework.
MAIN RESULTS
We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity.
AUTHORS' CONCLUSIONS
A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Review Literature as Topic; Time Factors
PubMed: 29084357
DOI: 10.1002/14651858.CD012509.pub2 -
Applied Ergonomics Nov 2022This paper systematically reviews 20 years of publications (N = 54) on aviation and neurophysiology. The main goal is to provide an account of neurophysiological... (Review)
Review
This paper systematically reviews 20 years of publications (N = 54) on aviation and neurophysiology. The main goal is to provide an account of neurophysiological changes associated with flight training with the aim of identifying neurometrics indicative of pilot's flight training level and task relevant mental states, as well as to capture the current state-of-art of (neuro)ergonomic design and practice in flight training. We identified multiple candidate neurometrics of training progress and workload, such as frontal theta power, the EEG Engagement Index and the Cognitive Stability Index. Furthermore, we discovered that several types of classifiers could be used to accurately detect mental states, such as the detection of drowsiness and mental fatigue. The paper advances practical guidelines on terminology usage, simulator fidelity, and multimodality, as well as future research ideas including the potential of Virtual Reality flight simulations for training, and a brain-computer interface for flight training.
Topics: Humans; Neurophysiology; Aviation; Workload; Virtual Reality; Ergonomics; Electroencephalography
PubMed: 35939991
DOI: 10.1016/j.apergo.2022.103838 -
Palliative Medicine Jan 2019End-stage liver disease is a common cause of morbidity and mortality worldwide, yet little is known about its symptomatology and impact on health-related quality of life. (Meta-Analysis)
Meta-Analysis
BACKGROUND:
End-stage liver disease is a common cause of morbidity and mortality worldwide, yet little is known about its symptomatology and impact on health-related quality of life.
AIM:
To describe symptom prevalence and health-related quality of life of patients with end-stage liver disease to improve care.
DESIGN:
Systematic review.
DATA SOURCES:
We searched eight electronic databases from January 1980 to June 2018 for studies investigating symptom prevalence or health-related quality of life of adult patients with end-stage liver disease. No language restrictions were applied. Meta-analyses were performed where appropriate.
RESULTS:
We included 80 studies: 35 assessing symptom prevalence, 41 assessing health-related quality of life, and 4 both. The instruments assessing symptoms varied across studies. The most frequently reported symptoms were as follows: pain (prevalence range 30%–79%), breathlessness (20%–88%), muscle cramps (56%–68%), sleep disturbance (insomnia 26%–77%, daytime sleepiness 29.5%–71%), and psychological symptoms (depression 4.5%–64%, anxiety 14%–45%). Erectile dysfunction was prevalent (53%–93%) in men. The health-related quality of life of patients with end-stage liver disease was significantly impaired when compared to healthy controls or patients with chronic liver disease. Compared with compensated cirrhosis, decompensation led to significant worsening of both components of the 36-Item Short Form Survey although to a larger degree for the Physical Component Summary score (decrease from average 6.4 (95% confidence interval: 4.0–8.8); p < 0.001) than for the Mental Component Summary score (4.5 (95% confidence interval: 2.4–6.6); p < 0.001).
CONCLUSION:
The symptom prevalence of patients with end-stage liver disease resembled that of patients with other advanced conditions. Given the diversity of symptoms and significantly impaired health-related quality of life, multidisciplinary approach and timely intervention are crucial.
Topics: Adult; Aged; Aged, 80 and over; End Stage Liver Disease; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Palliative Care; Prevalence; Quality of Life; Severity of Illness Index
PubMed: 30345878
DOI: 10.1177/0269216318807051 -
The Cochrane Database of Systematic... Dec 2020Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods.
OBJECTIVES
To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines.
SEARCH METHODS
We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
SELECTION CRITERIA
We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia.
DATA COLLECTION AND ANALYSIS
One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures.
MAIN RESULTS
We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines.
AUTHORS' CONCLUSIONS
When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
Topics: Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Anxiety; Bias; Clonidine; Drug Administration Schedule; Humans; Melatonin; Midazolam; Middle Aged; Oxazepam; Postoperative Care; Postoperative Complications; Preoperative Care; Publication Bias; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 33319916
DOI: 10.1002/14651858.CD009861.pub3 -
BMJ Clinical Evidence Jun 2009Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep... (Review)
Review
INTRODUCTION
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction. OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for severe obstructive sleep apnoea-hypopnoea syndrome? What are the effects of treatment for non-severe obstructive sleep apnoea-hypopnoea syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: nasal continuous positive airway pressure (CPAP); measures aimed at improving compliance with CPAP; oral appliances; and weight loss.
Topics: Arousal; Emotions; Health Status; Humans; Patient Satisfaction; Psychological Distance; Single-Blind Method; Sleep Apnea Syndromes; United States Food and Drug Administration
PubMed: 21726484
DOI: No ID Found -
Journal of Clinical Sleep Medicine :... Feb 2019The purpose of this systematic review is to provide supporting evidence for the clinical practice guideline for the treatment of obstructive sleep apnea (OSA) in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The purpose of this systematic review is to provide supporting evidence for the clinical practice guideline for the treatment of obstructive sleep apnea (OSA) in adults using positive airway pressure (PAP).
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of PAP with no treatment as well as studies that compared different PAP modalities. Meta-analyses were performed to determine the clinical significance of using PAP in several modalities (ie, continuous PAP, auto-adjusting PAP, and bilevel PAP), to treat OSA in adults. In addition, meta-analyses were performed to determine the clinical significance of using an in-laboratory versus ambulatory strategy for the initiation of PAP, educational and behavioral interventions, telemonitoring, humidification, different mask interfaces, and flexible or modified pressure profile PAP in conjunction with PAP to treat OSA in adults. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations.
RESULTS
The literature search resulted in 336 studies that met inclusion criteria; 184 studies provided data suitable for meta-analyses. The data demonstrated that PAP compared to no treatment results in a clinically significant reduction in disease severity, sleepiness, blood pressure, and motor vehicle accidents, and improvement in sleep-related quality of life in adults with OSA. In addition, the initiation of PAP in the home demonstrated equivalent effects on patient outcomes when compared to an in-laboratory titration approach. The data also demonstrated that the use of auto-adjusting or bilevel PAP did not result in clinically significant differences in patient outcomes compared with standard continuous PAP. Furthermore, data demonstrated a clinically significant improvement in PAP adherence with the use of educational, behavioral, troubleshooting, and telemonitoring interventions. Systematic reviews for specific PAP delivery method were also performed and suggested that nasal interfaces compared to oronasal interfaces have improved adherence and slightly greater reductions in OSA severity, heated humidification compared to no humidification reduces some continuous PAP-related side effects, and pressure profile PAP did not result in clinically significant differences in patient outcomes compared with standard continuous PAP.
Topics: Adult; Equipment Design; GRADE Approach; Humans; Patient Compliance; Positive-Pressure Respiration; Practice Guidelines as Topic; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 30736888
DOI: 10.5664/jcsm.7638 -
Multiple Sclerosis Journal -... 2023Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To... (Review)
Review
Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To better understand sleep-fatigue relationships in this population, we conducted a systematic review and random effects meta-analyses for the associations between fatigue and 10 sleep variables: Sleep-disordered breathing, daytime sleepiness, sleep quality, insomnia, restless legs, number of awakenings, sleep efficiency, sleep latency, sleep duration, and wake after sleep onset. Of the 1062 studies screened, 46 met inclusion criteria and provided sufficient data for calculating Hedges' g. Study quality was assessed using the Newcastle-Ottawa Scale. Sample characteristics did not differ between the 10 analyses. Results indicated that sleep quality and insomnia (assessed via self-report or diagnostic criteria) were strongly associated with fatigue (all s ≥ 0.80 and all < .001). In contrast, the number of awakenings and sleep duration (assessed objectively) were not significantly associated with fatigue. Remaining sleep variables yielded moderate, significant effects. Most effects did not vary based on study quality or sample demographics. Results highlight that insomnia and perceptions of poor sleep have a stronger link than objective sleep duration to fatigue in multiple sclerosis and may represent a more effective target for intervention.
PubMed: 37641617
DOI: 10.1177/20552173231194352 -
European Review For Medical and... Jul 2023The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy.
MATERIALS AND METHODS
A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals.
RESULTS
A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain.
CONCLUSIONS
Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis.
Topics: Adult; Child; Adolescent; Humans; Anticonvulsants; Epilepsies, Partial; Retrospective Studies; Prospective Studies; Epilepsy; Nitriles; Treatment Outcome
PubMed: 37458642
DOI: 10.26355/eurrev_202307_32957 -
The Cochrane Database of Systematic... Dec 2018Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice... (Review)
Review
BACKGROUND
Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy, cognitive behavioural therapy, sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as sleep difficulties, anxiety or depression. As yet, no drug has been approved for tinnitus by a regulatory body. Nonetheless, over 100,000 prescriptions for betahistine are being filled every month in England, and nearly 10% of general practitioners prescribe betahistine for tinnitus.
OBJECTIVES
To assess the effects of betahistine in patients with subjective idiopathic tinnitus.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 July 2018.
SELECTION CRITERIA
Randomised controlled trials (RCTs) recruiting patients of any age with acute or chronic subjective idiopathic tinnitus were included. We included studies where the intervention involved betahistine and this was compared to placebo, no intervention or education and information. We included all courses of betahistine, regardless of dose regimens or formulations and for any duration of treatment.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcomes included tinnitus loudness and significant adverse effects (upper gastrointestinal discomfort). Our secondary outcomes included tinnitus symptom severity as measured by the global score on a multi-item tinnitus questionnaire, depressive symptoms, symptoms of generalised anxiety, health-related quality of life, other adverse effects (e.g. headache, drowsiness, allergic skin reactions (pruritis, rashes) and exacerbation of tinnitus) and tinnitus intrusiveness. We used GRADE to assess the quality of evidence for each outcome; this is indicated in italics.
MAIN RESULTS
This review included five studies (with a total of 303 to 305 participants) comparing the effects of betahistine with placebo in adults with subjective idiopathic tinnitus. Four studies were parallel-group RCTs and one had a cross-over design. The risk of bias was unclear in all of the included studies.Due to heterogeneity in the outcomes measured and measurement methods used, very limited data pooling was possible. When we pooled the data from two studies for the primary outcome tinnitus loudness, the mean difference on a 0- to 10-point visual analogue scale at one-month follow-up was not significant between betahistine and placebo (-0.16, 95% confidence interval (CI) -1.01 to 0.70; 81 participants) (very low-quality evidence). There were no reports of upper gastrointestinal discomfort (significant adverse effect) in any study.As a secondary outcome, one study found no difference in the change in the Tinnitus Severity Index between betahistine and placebo (mean difference at 12 weeks 0.02, 95% CI -1.05 to 1.09; 50 participants) (moderate-quality evidence). None of the studies reported the other secondary outcomes of changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life as measured by a validated instrument, nor tinnitus intrusiveness.Other adverse effects that were reported were not treatment-related.
AUTHORS' CONCLUSIONS
There is an absence of evidence to suggest that betahistine has an effect on subjective idiopathic tinnitus when compared to placebo. The evidence suggests that betahistine is generally well tolerated with a similar risk of adverse effects to placebo treatments. The quality of evidence for the reported outcomes, using GRADE, ranged from moderate to very low.If future research into the effectiveness of betahistine in patients with tinnitus is felt to be warranted, it should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the development of validated, patient-centred outcome measures for research in the field of tinnitus.
PubMed: 30908589
DOI: 10.1002/14651858.CD013093.pub2