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BMJ Clinical Evidence Aug 2007Up to 18% of people in industrialised societies have mild tinnitus, which severely affects daily life in 0.5% of people. Tinnitus can be associated with hearing loss,... (Review)
Review
INTRODUCTION
Up to 18% of people in industrialised societies have mild tinnitus, which severely affects daily life in 0.5% of people. Tinnitus can be associated with hearing loss, acoustic neuromas, drug toxicity, ear diseases, and depression. Tinnitus can last for many years, and can interfere with sleep and concentration.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic tinnitus? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2006. (BMJ 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 37 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: acamprosate, acupuncture, antidepressant drugs, baclofen, benzodiazepines, carbamazepine, cinnarizine, ear-canal magnets, electromagnetic stimulation, ginkgo biloba, hearing aids, hyperbaric oxygen, hypnosis, lamotrigine, nicotinamide, psychotherapy, tinnitus-masking devices, tinnitus retraining therapy, zinc.
Topics: Tinnitus; United States
PubMed: 19454115
DOI: No ID Found -
Hepatology (Baltimore, Md.) Feb 2024The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce.
APPROACH AND RESULTS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.
CONCLUSION
MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.
Topics: Humans; Alcoholism; Alcohol Drinking; Acamprosate; Liver Cirrhosis, Alcoholic; Liver Cirrhosis
PubMed: 37625154
DOI: 10.1097/HEP.0000000000000570 -
Addiction (Abingdon, England) Jun 2015To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and... (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and treatment discontinuation, and to examine whether a proportion of the variance in study outcome can be explained by the country in which the trials have taken place.
METHOD
A systematic review and meta-analysis of randomized controlled trials published before September 2013 was conducted. The primary outcome measures were the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. Twenty-two randomized controlled trials (RCTs) of the efficacy of acamprosate met inclusion criteria for the meta-analysis, with a total of 2649 participants in the acamprosate group and 2587 in the placebo group. Twenty-seven RCTs of the efficacy of naltrexone met inclusion criteria for the meta-analysis, with a total of 2253 participants in the naltrexone group and 1946 in the placebo group. A random-effects model using a Mantel-Haenszel method was applied to conduct the meta-analysis. Variance in study outcomes was explored using subgroup analysis of Europe versus the rest of the world (ROW).
RESULTS
The risk of returning to any drinking at 6 months was significantly lower for acamprosate [risk ratio (RR) = 0.83, 95% confidence interval (CI) = 0.78-0.89]. There was little difference in the risk of participants discontinuing treatment for any reason (RR = 0.91, 95% CI = 0.83-1.00) or due to adverse events (RR = 1.30, 95% CI = 0.96-1.75) for the acamprosate compared to placebo groups. The risk of individuals returning to any drinking at approximately 3 months was reduced significantly for the naltrexone group (RR = 0.92, 95% CI = 0.86-1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR = 0.85, 95% CI = 0.78-0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR = 0.94, 95% CI = 0.84-1.05). There was a significantly greater risk of participants in the naltrexone group discontinuing treatment due to adverse events compared to placebo (RR = 1.72, 95% CI = 1.10-2.70). Subgroup analysis by country (Europe versus ROW) revealed no difference in risk between acamprosate and placebo for the outcomes returning to any drinking at 6 months and discontinuing treatment due to adverse events. For the outcome discontinuation of treatment for any reason, there was a significant difference in RR between Europe and the ROW (χ(2) = 11.65, P <0.001) for acamprosate. Acamprosate was associated with a reduction in risk of discontinuing treatment for Europe (RR = 0.86, 95% CI = 0.79-0.95), but an increase in risk of discontinuing treatment for ROW (RR = 1.23, 95% CI = 1.03-1.48).
CONCLUSIONS
Both acamprosate and naltrexone appear to reduce the risk of individuals returning to drinking alcohol in those who are alcohol-dependent. The country in which a randomized control trial (RCT) for the efficacy of acamprosate and naltrexone is completed does not appear to explain the variance in trial outcomes for returning to drinking alcohol or discontinuing drinking due to adverse effects. However, the country in which the RCT of acamprosate are completed may be important for explaining the variance between studies for the outcome 'discontinuing treatment for any reason'.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcoholism; Europe; Female; Global Health; Humans; Male; Middle Aged; Naltrexone; Randomized Controlled Trials as Topic; Recurrence; Taurine; Treatment Outcome
PubMed: 25664494
DOI: 10.1111/add.12875 -
Ugeskrift For Laeger Nov 2011The meta-analysis is based on 16 randomized controlled trials of acamprosate, 18 of naltrexone and 7 of disulfiram. Acamprosate and naltrexone were 52% (RR = 1.52; 95%... (Meta-Analysis)
Meta-Analysis Review
The meta-analysis is based on 16 randomized controlled trials of acamprosate, 18 of naltrexone and 7 of disulfiram. Acamprosate and naltrexone were 52% (RR = 1.52; 95% confidence interval (CI): 1.35-1,72) and 27% (RR = 1.27; 95% CI: 1,06-1,52) better than placebo when it came to supporting continuous abstinence. Acamprosate increased the total number of abstinence days with 14% (MD = 14.02; 95% CI: 9.57-18.47). Disulfiram appeared to be effective only when the intake was supervised. Based on the amount of scientific evidence, acamprosate and naltrexone therapy should be increased in clinical practice in the treatment of alcoholism.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Disulfiram; Evidence-Based Medicine; Humans; Naltrexone; Taurine; Treatment Outcome
PubMed: 22118653
DOI: No ID Found -
The Cochrane Database of Systematic... Sep 2010Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.
OBJECTIVES
To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents.
SEARCH STRATEGY
We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.
SELECTION CRITERIA
All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes.
MAIN RESULTS
24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).
AUTHORS' CONCLUSIONS
Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcohol-Related Disorders; Diarrhea; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Taurine
PubMed: 20824837
DOI: 10.1002/14651858.CD004332.pub2 -
The Cochrane Database of Systematic... Jan 2023Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide,... (Review)
Review
BACKGROUND
Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was 22 November 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. relapse, 2. frequency of use, 3. amount of use, 4. adverse events, 5. dropouts from treatment and 6. dropouts from treatment due to adverse events. Our secondary outcomes were 7. craving, 8. anxiety, 9. depression and 10. frequency of most relevant adverse events.
MAIN RESULTS
We included 17 RCTs (1818 participants) with a diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or International Classification of Diseases 10th edition criteria. Mean age was 46.5 years and 70% were men. Ten studies compared baclofen to placebo or another medication; seven compared two baclofen doses to placebo or another medication. Globally, 15 studies compared baclofen to placebo, two baclofen to acamprosate and two baclofen to naltrexone. In 16 studies, participants received psychosocial treatments. We judged most studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. Ten studies detoxified participants before treatment; in seven studies, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 RCTs and longer in two studies. Baclofen daily dose was 30 mg to 300 mg: 10 RCTs used low doses (30 mg or less); eight RCTs medium doses (above 30 and 100 mg or less) and four RCTs high doses (above 100 mg). Compared to placebo, moderate-certainty evidence found that baclofen probably decreases the risk to relapse (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.77 to 0.99; 12 studies, 1057 participants). This result was confirmed among detoxified participants but not among other subgroups of participants. High-certainty evidence found that baclofen increases the percentage of days abstinent (mean difference (MD) 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all subgroups of participants except non-detoxified or those who received medium doses. There was no difference between baclofen and placebo in the other primary outcomes: heavy drinking days (standardised mean difference (SMD) -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants; moderate-certainty evidence); number of drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants; moderate-certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants; high-certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03; 17 studies, 1563 participants; high-certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants; high-certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.16, 95% CI -0.37 to 0.04; 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 studies, 1123 participants) and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, baclofen increases fatigue, dizziness, somnolence/sedation, dry mouth, paraesthesia and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, one study (60 participants) found no differences in any outcomes but the evidence was very uncertain: relapse (RR 1.25, 95% CI 0.71 to 2.20; very low-certainty evidence); number of participants with at least one adverse event (RR 0.63, 95% CI 0.23 to 1.69; very low-certainty evidence); dropouts (RR 0.56, 95% CI 0.21 to 1.46; very low-certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01 to 7.87; very low-certainty evidence) and craving (MD 5.80, 95% CI -11.84 to 23.44); and all the adverse events evaluated. Compared to naltrexone, baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12 to 5.56; 1 study, 60 participants; very low-certainty evidence) and decrease the number of participants with at least one adverse event (RR 0.35, 95% CI 0.15 to 0.80; 2 studies, 80 participants; very low-certainty evidence) but the evidence is very uncertain. One study (60 participants) found no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32 to 3.10; very low-certainty evidence), craving (MD 2.08, 95% CI -3.71 to 7.87), and all the adverse events evaluated.
AUTHORS' CONCLUSIONS
Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study.
Topics: Adult; Female; Humans; Male; Middle Aged; Acamprosate; Alcohol Drinking; Alcoholism; Baclofen; Chronic Disease; Naltrexone
PubMed: 36637087
DOI: 10.1002/14651858.CD012557.pub3 -
PloS One 2022The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine...
AIM
The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine the reliability of the adherence monitoring and measurement methods used in these trials.
METHODS
The protocol for this review was pre-registered (PROSPERO: CRD42021230011). A search of the literature was conducted using OVID MEDLINE, Embase and PsycINFO from database inception to January 2021. Randomised controlled trials with a minimum sample size of 10 per treatment arm that compared the efficacy of acamprosate with placebo or other active medication in adults with a diagnosis of alcohol dependence were included. Data on rates of adherence, methods of measurement and monitoring of adherence was extracted from eligible studies independently in duplicate by two reviewers. A weighted mean adherence rate was calculated. The reliability of adherence monitoring methods was determined by calculating an adherence-assurance score based on the adherence monitoring method used. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
RESULTS
Fifteen studies met the eligibility criteria involving 4,450 participants (2,480 participants in the placebo arms). A mean adherence rate of 88% (54.2-95.0%) was reported across studies that reported the percentage of medication taken. A mean adherence rate of 84.9% (56.4-91.3%) was reported for trials that reported the percentage of participants taking more than 80% of medication prescribed. There is low confidence in the methods used to monitor adherence with all clinical trials having a low adherence-assurance rating. Risk of bias was judged to be high for all included studies.
CONCLUSIONS
Adherence to acamprosate in clinical trials can be poor with low confidence in the methods used to measure it. Adherence rates therefore might not be accurate, which has implications for determining the efficacy of acamprosate.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcoholism; Clinical Decision-Making; Humans; Medication Adherence; Middle Aged; Randomized Controlled Trials as Topic; Reproducibility of Results
PubMed: 35113930
DOI: 10.1371/journal.pone.0263350 -
Current Neuropharmacology 2020Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited,...
BACKGROUND
Pharmacological treatment for alcohol dependence has only three approved drugs: disulfiram, naltrexone and acamprosate. The effects of these drugs are, however, limited, presenting several side effects and a modestly higher efficacy compared to placebo. The administration of omega-3 might bring new perspectives to relapse prevention.
METHODS
This systematic review aimed to analyze the available literature, compiling the studies that used omega-3 to prevent relapse in alcohol dependents.
RESULTS
The databases used were PubMed and Web of Science. We identified 2,231 studies and only five articles addressed the administration of omega-3 and alcoholism. Preclinical studies evaluating the effects of PUFAs related to chronic alcohol administration showed improvements in behavioral, cellular and molecular levels. The clinical trial yielded inconclusive results.
CONCLUSION
Despite the reduced number of studies, omega-3 interventions seem to be promising for controlling issues related to alcohol dependence.
Topics: Alcoholism; Animals; Behavior, Animal; Clinical Trials as Topic; Fatty Acids, Omega-3; Humans; Secondary Prevention; Treatment Outcome
PubMed: 31989899
DOI: 10.2174/1570159X18666200128120729 -
Frontiers in Pharmacology 2019Sleep disorders are commonly associated with acute and chronic use of alcohol and with abstinence. To date, there are four approved drugs to treat alcohol use disorder...
Sleep disorders are commonly associated with acute and chronic use of alcohol and with abstinence. To date, there are four approved drugs to treat alcohol use disorder (AUD): disulfiram, acamprosate, naltrexone, and nalmefene. These AUD therapies reduce the craving and risk of relapse into heavy drinking, but little is known about their effect on sleep. As recent evidences indicate a crucial role of sleep disorders in AUD, claiming that sleep problems may trigger alcohol abuse and relapses, it is fundamental to clarify the impact of those drugs on the sleep quality of AUD patients. This systematic review aims to answer the question: how does the pharmacotherapy for AUD affect sleep? We searched PubMed, Embase, CINAHL Plus, Cochrane, and Scopus using sleep- and AUD pharmacotherapy-related keywords. The articles included were appraised using the CASP checklists, and the risk of bias was assessed following the Cochrane risk-of-bias assessment tool. Finally, we pooled sleep outcomes in a meta-analysis to measure the overall effect. We included 26 studies: only three studies focused on sleep as a main outcome, two with polysomnography (objective measurement), and one with subjective self-reported sleep, while all the other studies reported sleep problems among the adverse effects (subjective report). The only study available on disulfiram showed reduced REM sleep. Acamprosate showed no/little effect on self-reported sleep but improved sleep continuity and architecture measured by polysomnography. The two opioidergic drugs naltrexone and nalmefene had mainly detrimental effect on sleep, giving increased insomnia and/or somnolence compared with placebo, although not always significant. The meta-analysis confirmed significantly increased somnolence and insomnia in the naltrexone group, compared with the placebo. Overall, the currently available evidences show more sleep problems with the opioidergic drugs (especially naltrexone), while acamprosate seems to be well tolerated or even beneficial. Acamprosate might be a more suitable choice when patients with AUD report sleep problems. Due to the paucity of information available, and with the majority of results being subjective, more research on this topic is needed to further inform the clinical practice, ideally with more objective measurements such as polysomnography.
PubMed: 31680952
DOI: 10.3389/fphar.2019.01164