-
Effects of dietary supplements on athletic performance in elite soccer players: a systematic review.Journal of the International Society of... Dec 2023Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to... (Review)
Review
Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to enhance performance in soccer is somewhat contradictory, scarce, or even nonexistent. Thus, the present study aimed to systematically review and synthesize the effects of dietary supplements on athletic performance (e.g. distance covered, sprinting, jump performance) in elite soccer players. Studies enrolling highly trained, elite, and world-class soccer players using dietary supplements were searched in MEDLINE/PubMed, Web of Science, Scopus, and EBSCO databases in June 2022. In total, 1043 studies were identified, and 18 met the eligibility criteria. The studies evaluated the impacts on athletic performance of several dietary supplements, including caffeine, creatine, protein, beverages with carbohydrates and electrolytes, tart cherry juice, nitrate-rich beetroot juice, sodium bicarbonate with minerals, yohimbine, and a proprietary nutraceutical blend. Caffeine supplementation in doses between 3 and 6 mg/kg of body mass may improve jump height and sprint ability, particularly in female players, but individual response to caffeine must be considered. Creatine may improve sprint, agility, and in female players, jump performance. Protein supplementation can improve sprint and jump performance between matches, especially if protein ingested from food is not up to recommendations. Beverages containing carbohydrates and electrolytes can be used as part of the strategies to achieve carbohydrate intake during training and match-days but used alone do not benefit athletic performance. Tart cherry juice might be useful for maintaining athletic performance after matches that produce higher force loss and exercise-induced muscle damage, although polyphenols from the diet might attenuate the effects of tart cherry supplementation. Nitrate-rich beetroot concentrate can attenuate performance decrease in the days following matches. Further investigation with sodium bicarbonate alone is necessary, as supplementation protocols with elite players included other substances. Finally, the available data does not support yohimbine supplementation or the use of Resurgex Plus® to improve athletic performance in elite soccer players. Still, more well-designed research with elite soccer players is needed to improve support and advice regarding the use of dietary supplements for athletic performance enhancement.
Topics: Humans; Female; Soccer; Caffeine; Sodium Bicarbonate; Creatine; Nitrates; Athletic Performance; Dietary Supplements; Electrolytes; Carbohydrates
PubMed: 37462346
DOI: 10.1080/15502783.2023.2236060 -
Nutrients Apr 2023According to reports, supplementation with appropriate doses of taurine may help to reduce visual fatigue. Presently, some progress has been made in research related to... (Review)
Review
According to reports, supplementation with appropriate doses of taurine may help to reduce visual fatigue. Presently, some progress has been made in research related to taurine in eye health, but the lack of systematic summaries has led to the neglect of its application in the relief of visual fatigue. This paper, therefore, provides a systematic review of the sources of taurine, including the endogenous metabolic and exogenous dietary pathways, as well as a detailed review of the distribution and production of exogenous taurine. The physiological mechanisms underlying the production of visual fatigue are summarized and the research progress of taurine in relieving visual fatigue is reviewed, including the safety of consumption and the mechanism of action in relieving visual fatigue, in order to provide some reference basis and inspiration for the development and application of taurine in functional foods for relieving visual fatigue.
Topics: Humans; Taurine; Asthenopia; Diet; Functional Food; Dietary Supplements
PubMed: 37111062
DOI: 10.3390/nu15081843 -
Neuroscience and Biobehavioral Reviews Aug 2022The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to... (Review)
Review
The use of low doses of psychedelic substances (microdosing) is attracting increasing interest. This systematic review summarises all empirical microdosing research to date, including a set of infrequently cited studies that took place prior to prohibition. Specifically, we reviewed 44 studies published between 1955 and 2021, and summarised reported effects across six categories: mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias, depending on design, age, and other study characteristics. Laboratory studies found changes in pain perception, time perception, conscious state, and neurophysiology. Self-report studies found changes in cognitive processing and mental health. We review data related to expectation and placebo effects, but argue that claims that microdosing effects are largely due to expectancy are premature and possibly wrong. In addition, we attempt to clarify definitional inconsistencies in the microdosing literature by providing suggested dose ranges across different substances. Finally, we provide specific design suggestions to facilitate more rigorous future research.
Topics: Affect; Creativity; Hallucinogens; Humans; Mental Health; Personality; Psilocybin
PubMed: 35609684
DOI: 10.1016/j.neubiorev.2022.104706 -
European Review For Medical and... Apr 2015Ginger (Zingiber officinale) is a spice traditionally used to treat indigestion, nausea and vomiting. Ginger extracts accelerate gastric emptying and stimulate gastric... (Review)
Review
Ginger (Zingiber officinale) is a spice traditionally used to treat indigestion, nausea and vomiting. Ginger extracts accelerate gastric emptying and stimulate gastric antral contractions. These effects are mainly due to the presence of gingerols and shogaols and their activity on cholinergic M receptors and serotonergic 5-HT and 5-HT receptors. Various researches on this subject have led to controversial results, due to the chemical instability of ginger extracts and particularly of gingerols, which are readily-oxidizable substances. A systematic review of double-blind, placebo-controlled, randomized studies highlighted the potential efficacy of ginger on the prevention and treatment of nausea and vomiting of various origins, even though additional controlled studies are needed. This review focuses on pregnancy-induced nausea and vomiting and on chemotherapy induced nausea, and hypothesizes a therapeutic role for ginger extracts in case of side effects, as an alternative to traditional prokinetic drugs such as domperidone, levosulpiride or metoclopramide.
Topics: Animals; Antiemetics; Antineoplastic Agents; Catechols; Fatty Alcohols; Female; Gastric Emptying; Zingiber officinale; Humans; Nausea; Plant Extracts; Pregnancy; Pregnancy Complications; Vomiting
PubMed: 25912592
DOI: No ID Found -
Nutrients Feb 2019Soccer is a complex team sport and success in this discipline depends on different factors such as physical fitness, player technique and team tactics, among others. In...
Soccer is a complex team sport and success in this discipline depends on different factors such as physical fitness, player technique and team tactics, among others. In the last few years, several studies have described the impact of caffeine intake on soccer physical performance, but the results of these investigations have not been properly reviewed and summarized. The main objective of this review was to evaluate critically the effectiveness of a moderate dose of caffeine on soccer physical performance. A structured search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in the Medline/PubMed and Web of Science databases from January 2007 to November 2018. The search included studies with a cross-over and randomized experimental design in which the intake of caffeine (either from caffeinated drinks or pills) was compared to an identical placebo situation. There were no filters applied to the soccer players' level, gender or age. This review included 17 articles that investigated the effects of caffeine on soccer-specific abilities ( = 12) or on muscle damage ( = 5). The review concluded that 5 investigations (100% of the number of investigations on this topic) had found ergogenic effects of caffeine on jump performance, 4 (100%) on repeated sprint ability and 2 (100%) on running distance during a simulated soccer game. However, only 1 investigation (25%) found as an effect of caffeine to increase serum markers of muscle damage, while no investigation reported an effect of caffeine to reduce perceived fatigue after soccer practice. In conclusion, a single and moderate dose of caffeine, ingested 5⁻60 min before a soccer practice, might produce valuable improvements in certain abilities related to enhanced soccer physical performance. However, caffeine does not seem to cause increased markers of muscle damage or changes in perceived exertion during soccer practice.
Topics: Adolescent; Adult; Athletic Performance; Caffeine; Cross-Over Studies; Dietary Supplements; Fatigue; Female; Humans; Male; Muscle, Skeletal; Perception; Performance-Enhancing Substances; Physical Functional Performance; Randomized Controlled Trials as Topic; Running; Soccer; Young Adult
PubMed: 30791576
DOI: 10.3390/nu11020440 -
The Cochrane Database of Systematic... Oct 2021Substance use disorders (SUDs) are highly prevalent and associated with a substantial public health burden. Although evidence-based interventions exist for treating... (Review)
Review
BACKGROUND
Substance use disorders (SUDs) are highly prevalent and associated with a substantial public health burden. Although evidence-based interventions exist for treating SUDs, many individuals remain symptomatic despite treatment, and relapse is common.Mindfulness-based interventions (MBIs) have been examined for the treatment of SUDs, but available evidence is mixed.
OBJECTIVES
To determine the effects of MBIs for SUDs in terms of substance use outcomes, craving and adverse events compared to standard care, further psychotherapeutic, psychosocial or pharmacological interventions, or instructions, waiting list and no treatment.
SEARCH METHODS
We searched the following databases up to April 2021: Cochrane Drugs and Alcohol Specialised Register, CENTRAL, PubMed, Embase, Web of Science, CINAHL and PsycINFO. We searched two trial registries and checked the reference lists of included studies for relevant randomized controlled trials (RCTs).
SELECTION CRITERIA
RCTs testing a MBI versus no treatment or another treatment in individuals with SUDs. SUDs included alcohol and/or drug use disorders but excluded tobacco use disorders. MBIs were defined as interventions including training in mindfulness meditation with repeated meditation practice. Studies in which SUDs were formally diagnosed as well as those merely demonstrating elevated SUD risk were eligible.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Forty RCTs met our inclusion criteria, with 35 RCTs involving 2825 participants eligible for meta-analysis. All studies were at high risk of performance bias and most were at high risk of detection bias. Mindfulness-based interventions (MBIs) versus no treatment Twenty-four RCTs included a comparison between MBI and no treatment. The evidence was uncertain about the effects of MBIs relative to no treatment on all primary outcomes: continuous abstinence rate (post: risk ratio (RR) = 0.96, 95% CI 0.44 to 2.14, 1 RCT, 112 participants; follow-up: RR = 1.04, 95% CI 0.54 to 2.01, 1 RCT, 112 participants); percentage of days with substance use (post-treatment: standardized mean difference (SMD) = 0.05, 95% CI -0.37 to 0.47, 4 RCTs, 248 participants; follow-up: SMD = 0.21, 95% CI -0.12 to 0.54, 3 RCTs, 167 participants); and consumed amount (post-treatment: SMD = 0.10, 95% CI -0.31 to 0.52, 3 RCTs, 221 participants; follow-up: SMD = 0.33, 95% CI 0.00 to 0.66, 2 RCTs, 142 participants). Evidence was uncertain for craving intensity and serious adverse events. Analysis of treatment acceptability indicated MBIs result in little to no increase in study attrition relative to no treatment (RR = 1.04, 95% CI 0.77 to 1.40, 21 RCTs, 1087 participants). Certainty of evidence for all other outcomes was very low due to imprecision, risk of bias, and/or inconsistency. Data were unavailable to evaluate adverse events. Mindfulness-based interventions (MBIs) versus other treatments (standard of care, cognitive behavioral therapy, psychoeducation, support group, physical exercise, medication) Nineteen RCTs included a comparison between MBI and another treatment. The evidence was very uncertain about the effects of MBIs relative to other treatments on continuous abstinence rate at post-treatment (RR = 0.80, 95% CI 0.45 to 1.44, 1 RCT, 286 participants) and follow-up (RR = 0.57, 95% CI 0.28 to 1.16, 1 RCT, 286 participants), and on consumed amount at post-treatment (SMD = -0.42, 95% CI -1.23 to 0.39, 1 RCT, 25 participants) due to imprecision and risk of bias. The evidence suggests that MBIs reduce percentage of days with substance use slightly relative to other treatments at post-treatment (SMD = -0.21, 95% CI -0.45 to 0.03, 5 RCTs, 523 participants) and follow-up (SMD = -0.39, 95% CI -0.96 to 0.17, 3 RCTs, 409 participants). The evidence was very uncertain about the effects of MBIs relative to other treatments on craving intensity due to imprecision and inconsistency. Analysis of treatment acceptability indicated MBIs result in little to no increase in attrition relative to other treatments (RR = 1.06, 95% CI 0.89 to 1.26, 14 RCTs, 1531 participants). Data were unavailable to evaluate adverse events.
AUTHORS' CONCLUSIONS
In comparison with no treatment, the evidence is uncertain regarding the impact of MBIs on SUD-related outcomes. MBIs result in little to no higher attrition than no treatment. In comparison with other treatments, MBIs may slightly reduce days with substance use at post-treatment and follow-up (4 to 10 months). The evidence is uncertain regarding the impact of MBIs relative to other treatments on abstinence, consumed substance amount, or craving. MBIs result in little to no higher attrition than other treatments. Few studies reported adverse events.
Topics: Cognitive Behavioral Therapy; Craving; Humans; Mindfulness; Randomized Controlled Trials as Topic; Recurrence; Substance-Related Disorders
PubMed: 34668188
DOI: 10.1002/14651858.CD011723.pub2 -
Journal of General Internal Medicine Dec 2019Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder.
METHODS
We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacological interventions in adults with cocaine use disorder. When possible, we combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed the risk of bias of individual trials and the strength of evidence for each outcome using standardized criteria. Outcomes included continuous abstinence (3+ consecutive weeks); cocaine use; harms; and study retention. For relapse prevention studies (participants abstinent at baseline), we examined lapse (first cocaine positive or missing UDS) and relapse (two consecutive cocaine positive or missed UDS').
RESULTS
Sixty-six different drugs or drug combinations were studied in seven systematic reviews and 48 RCTs that met inclusion criteria. Antidepressants were the most widely studied drug class (38 RCTs) but appear to have no effect on cocaine use or treatment retention. Increased abstinence was found with bupropion (2 RCTs: RR 1.63, 95% CI 1.02 to 2.59), topiramate (2 RCTs: RR 2.56, 95% CI 1.39 to 4.73), and psychostimulants (14 RCTs: RR 1.36, 95% CI 1.05 to 1.77), though the strength of evidence for these findings was low. We found moderate strength of evidence that antipsychotics improved treatment retention (8 RCTs: RR 1.33, 95% CI 1.03 to 1.75).
DISCUSSION
Most of the pharmacotherapies studied were not effective for treating cocaine use disorder. Bupropion, psychostimulants, and topiramate may improve abstinence, and antipsychotics may improve retention. Contingency management and behavioral interventions along with pharmacotherapy should continue to be explored.
SR REGISTRATION
Prospero CRD42018085667.
Topics: Antidepressive Agents; Antipsychotic Agents; Central Nervous System Agents; Cocaine; Cocaine-Related Disorders; Drug Therapy; Humans
PubMed: 31183685
DOI: 10.1007/s11606-019-05074-8 -
The Cochrane Database of Systematic... Dec 2021Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is... (Review)
Review
BACKGROUND
Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002.
OBJECTIVES
To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, and LILACS databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 20 July 2021.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) (including cluster-randomised trials and first phase cross-over studies) that used injection sclerotherapy for the treatment of varicose veins.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed, selected and extracted data. Disagreements were cross-checked by a third review author. We used Cochrane's Risk of bias tool to assess the risk of bias. The outcomes of interest were cosmetic appearance, complications, residual varicose veins, quality of life (QoL), persistence of symptoms, and recurrent varicose veins. We calculated risk ratios (RRs) or mean difference (MD) with 95% confidence intervals (CIs). We used the worst-case-scenario for dichotomous data imputation for intention-to-treat analyses. For continuous outcomes, we used the 'last-observation-carried-forward' for data imputation if there was balanced loss to follow-up. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 23 new RCTs for this update, bringing the total to 28 studies involving 4278 participants. The studies differed in their design, and in which sclerotherapy method, agent or concentration was used. None of the included RCTs compared sclerotherapy to no intervention or to any pharmacological therapy. The certainty of the evidence was downgraded for risk of bias, low number of studies providing information for each outcome, low number of participants, clinical differences between the study participants, and wide CIs. Sclerotherapy versus placebo Foam sclerotherapy may improve cosmetic appearance as measured by IPR-V (independent photography review - visible varicose veins scores) compared to placebo (polidocanol 1%: mean difference (MD) -0.76, 95% CI -0.91 to -0.60; 2 studies, 223 participants; very low-certainty evidence); however, deep vein thrombosis (DVT) rates may be slightly increased in this intervention group (RR 5.10, 95% CI 1.30 to 20.01; 3 studies, 302 participants; very low-certainty evidence). Residual varicose vein rates may be decreased following polidocanol 1% compared to placebo (RR 0.19, 95% CI 0.13 to 0.29; 2 studies, 225 participants; very low-certainty evidence). Following polidocanol 1% use, there may be a possible improvement in QoL as assessed using the VEINES-QOL/Sym questionnaire (MD 12.41, 95% CI 9.56 to 15.26; 3 studies, 299 participants; very low-certainty evidence), and possible improvement in varicose vein symptoms as assessed using the Venous Clinical Severity Score (VCSS) (MD -3.25, 95% CI -3.90 to -2.60; 2 studies, 223 participants; low-certainty evidence). Recurrent varicose veins were not reported for this comparison. Foam sclerotherapy versus foam sclerotherapy with different concentrations Three individual RCTs reported no evidence of a difference in cosmetic appearance after comparing different concentrations of the intervention; data could not be pooled for two of the three studies (RR 1.11, 95% CI 0.84 to 1.47; 1 study, 80 participants; very low-certainty evidence). Similarly, there was no clear difference in rates of thromboembolic complications when comparing one foam concentration with another (RR 1.47, 95% CI 0.41 to 5.33; 3 studies, 371 participants; very low-certainty evidence). Three RCTs investigating higher concentrations of polidocanol foam indicated the rate of residual varicose veins may be slightly decreased in the polidocanol 3% foam group compared to 1% (RR 0.67, 95% CI 0.43 to 1.04; 3 studies, 371 participants; moderate-certainty evidence). No clear improvement in QoL was detected. Two RCTs reported improved VCSS scores with increasing concentrations of foam. Persistence of symptoms were not reported for this comparison. There was no clear difference in recurrent varicose vein rates (RR 0.91, 95% CI 0.62 to 1.32; 1 study, 148 participants; low-certainty evidence). Foam sclerotherapy versus liquid sclerotherapy One RCT reported on cosmetic appearance with no evidence of a difference between foam or liquid sclerotherapy (patient satisfaction scale MD 0.2, 95% CI -0.27 to 0.67; 1 study, 126 participants; very low-certainty evidence). None of the RCTs investigated thromboembolic complications, QoL or persistence of symptoms. Six studies individually showed there may be a benefit to polidocanol 3% foam over liquid sclerotherapy in reducing residual varicose vein rate; pooling data from two studies showed a RR of 0.51, with 95% CI 0.41 to 0.65; 203 participants; very low-certainty evidence. One study reported no clear difference in recurrent varicose vein rates when comparing sodium tetradecyl sulphate (STS) foam or liquid (RR 1.10, 95% CI 0.86 to 1.42; 1 study, 286 participants; very low-certainty evidence). Sclerotherapy versus sclerotherapy with different substances Four RCTs compared sclerotherapy versus sclerotherapy with any other substance. We were unable to combine the data due to heterogeneity or assess the certainty of the evidence due to insufficient data.
AUTHORS' CONCLUSIONS
There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence.
Topics: Humans; Sclerotherapy; Varicose Ulcer; Varicose Veins; Veins; Venous Insufficiency
PubMed: 34883526
DOI: 10.1002/14651858.CD001732.pub3 -
Nutrients Mar 2021Cognitive functions are essential in any form of exercise. Recently, interest has mounted in addressing the relationship between caffeine intake and cognitive... (Meta-Analysis)
Meta-Analysis
Cognitive functions are essential in any form of exercise. Recently, interest has mounted in addressing the relationship between caffeine intake and cognitive performance during sports practice. This review examines this relationship through a structured search of the databases Medline/PubMed and Web of Science for relevant articles published in English from August 1999 to March 2020. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PICOS model. The identified records reported on randomized cross-over studies in which caffeine intake (as drinks, capsules, energy bars, or gum) was compared to an identical placebo situation. There were no filters on participants' training level, gender, or age. For the systematic review, 13 studies examining the impacts of caffeine on objective measures of cognitive performance or self-reported cognitive performance were selected. Five of these studies were also subjected to meta-analysis. After pooling data in the meta-analysis, the significant impacts of caffeine only emerged on attention, accuracy, and speed. The results of the 13 studies, nevertheless, suggest that the intake of a low/moderate dose of caffeine before and/or during exercise can improve self-reported energy, mood, and cognitive functions, such as attention; it may also improve simple reaction time, choice reaction time, memory, or fatigue, however, this may depend on the research protocols.
Topics: Adult; Athletes; Athletic Performance; Caffeine; Cognition; Female; Humans; Male; Performance-Enhancing Substances; Randomized Controlled Trials as Topic
PubMed: 33800853
DOI: 10.3390/nu13030868 -
The Cochrane Database of Systematic... Mar 2018Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering.
OBJECTIVES
To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use.
SEARCH METHODS
We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions.
AUTHORS' CONCLUSIONS
Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.
Topics: Adult; Antidepressive Agents; Aspartic Acid; Benzodiazepines; Buspirone; Carbamazepine; Ethylamines; Flumazenil; Homeopathy; Humans; Imidazoles; Lithium Compounds; Melatonin; Paroxetine; Pregabalin; Progesterone; Pyridines; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Sulfides; Withholding Treatment
PubMed: 29543325
DOI: 10.1002/14651858.CD011481.pub2