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The Cochrane Database of Systematic... Nov 2019Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. Baclofen shows potential for rapidly reducing symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review first published in 2011 and last updated in 2017.
OBJECTIVES
To assess the efficacy and safety of baclofen for people with AWS.
SEARCH METHODS
We updated our searches of the following databases to June 2019: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.
SELECTION CRITERIA
We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving. For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence). For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available.
AUTHORS' CONCLUSIONS
No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence.
Topics: Alcoholism; Baclofen; Craving; GABA Agonists; Humans; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 31689723
DOI: 10.1002/14651858.CD008502.pub6 -
Journal of Rehabilitation Medicine Mar 2017Oral baclofen has long been a mainstay in the management of spasticity. This review looks at the clinical evidence for the efficacy and safety of oral baclofen in... (Review)
Review
Oral baclofen has long been a mainstay in the management of spasticity. This review looks at the clinical evidence for the efficacy and safety of oral baclofen in patients with spasticity of any origin or severity, to determine whether there is a rationale for the use of intrathecal baclofen. Results suggest that oral baclofen may be effective in many patients with spasticity, regardless of the underlying disease or severity, and that it is at least comparable with other antispasmodic agents. However, adverse effects, such as muscle weakness, nausea, somnolence and paraesthesia, are common with oral baclofen, affecting between 25% and 75% of patients, and limiting its usefulness. Intrathecal baclofen may be an effective alternative as the drug is delivered directly into the cerebrospinal fluid, thus bypassing the blood-brain barrier and thereby optimizing the efficacy of baclofen while minimizing drug-related side-effects. Intrathecal baclofen is a viable option in patients who experience intolerable side-effects or who fail to respond to the maximum recommended dose of oral baclofen.
Topics: Administration, Oral; Adult; Baclofen; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Female; Humans; Injections, Spinal; Male; Muscle Relaxants, Central; Muscle Spasticity; Muscle Weakness; Nausea; Parasympatholytics
PubMed: 28233010
DOI: 10.2340/16501977-2211 -
European Addiction Research 2013It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some... (Review)
Review
BACKGROUND
It has been reported that baclofen, a drug used in the treatment of spasticity, reduces the severity of withdrawal symptoms and substance use disorders (SUDs) for some psychoactive drugs.
AIMS AND METHODS
To evaluate the effectiveness and safety of baclofen in the treatment of withdrawal syndrome and/or SUDs, providing (1) an outline of its pharmacological features; (2) a summary of studies that have suggested its possible effectiveness in the treatment of SUDs, and (3) a review of randomized, controlled trials (RCTs) on baclofen and SUDs.
RESULTS
Baclofen tolerability is generally considered to be good. Eleven RCTs investigated its effectiveness in the treatment of SUDs. Of these, 5 RCTs found that baclofen is effective, 5 RCTs found that it is ineffective and the results of 1 RCT were not appreciable because it did not achieve the preplanned level of participation.
CONCLUSIONS
The number of RCTs on baclofen and SUDs is still low, and their results are divergent. Further RCTs should be undertaken, particularly with higher doses of baclofen. Its administration may be suggested in patients who fail to respond to other approved drugs or who are affected by liver disease that prevents their administration, or in patients affected by SUDs for which no approved drugs are available. Treatment should be conducted under strict medical supervision.
Topics: Baclofen; GABA-B Receptor Agonists; Humans; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome
PubMed: 23775042
DOI: 10.1159/000347055 -
European Journal of Clinical... Mar 2018Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential... (Review)
Review
PURPOSE
Gamma-hydroxybutyrate (GHB) withdrawal is a life-threatening condition that does not always respond to standard treatment with benzodiazepines. Baclofen has potential utility as a pharmacological adjunct and anecdotal reports suggest that it is being used by drug users to self-manage GHB withdrawal symptoms. Here, we investigate current patterns of use and the online availably of baclofen.
METHODS
Data triangulation techniques were applied to published scientific literature and publicly accessible Internet resources (grey literature) to assess the use of baclofen in GHB withdrawal. An Internet snapshot survey was performed to identify the availability of baclofen for online purchase and the compliance of retailers with the UK regulations. Data were collected according to pre-defined criteria.
RESULTS
A total of 37 cases of baclofen use in GHB withdrawal were identified in the scientific literature, as well as 51 relevant discussion threads across eight Internet forums in the grey literature. Baclofen was available to purchase from 38 online pharmacies, of which only one conformed to the UK regulations.
CONCLUSIONS
There is limited published evidence on the use of baclofen in GHB withdrawal, but both scientific and grey literature suggests clinical utility. Online pharmacies are readily offering prescription-only-medication without prescription and due to inadequate regulation, pose a danger to the public.
Topics: Animals; Baclofen; Biomedical Research; Drug Trafficking; GABA-B Receptor Agonists; Humans; Internet; Pharmaceutical Services, Online; Practice Patterns, Physicians'; Prescription Drugs; Psychotropic Drugs; Social Media; Sodium Oxybate; Substance Withdrawal Syndrome; United Kingdom
PubMed: 29198063
DOI: 10.1007/s00228-017-2387-z -
Journal of Neurophysiology Mar 2019Although motion of the head and body has been suspected or known as the provocative cause for the production of motion sickness for centuries, it is only within the last... (Review)
Review
Although motion of the head and body has been suspected or known as the provocative cause for the production of motion sickness for centuries, it is only within the last 20 yr that the source of the signal generating motion sickness and its neural basis has been firmly established. Here, we briefly review the source of the conflicts that cause the body to generate the autonomic signs and symptoms that constitute motion sickness and provide a summary of the experimental data that have led to an understanding of how motion sickness is generated and can be controlled. Activity and structures that produce motion sickness include vestibular input through the semicircular canals, the otolith organs, and the velocity storage integrator in the vestibular nuclei. Velocity storage is produced through activity of vestibular-only (VO) neurons under control of neural structures in the nodulus of the vestibulo-cerebellum. Separate groups of nodular neurons sense orientation to gravity, roll/tilt, and translation, which provide strong inhibitory control of the VO neurons. Additionally, there are acetylcholinergic projections from the nodulus to the stomach, which along with other serotonergic inputs from the vestibular nuclei, could induce nausea and vomiting. Major inhibition is produced by the GABA receptors, which modulate and suppress activity in the velocity storage integrator. Ingestion of the GABA agonist baclofen causes suppression of motion sickness. Hopefully, a better understanding of the source of sensory conflict will lead to better ways to avoid and treat the autonomic signs and symptoms that constitute the syndrome.
Topics: Animals; Baclofen; GABA-B Receptor Agonists; Humans; Motion Sickness; Vestibular Nuclei; Vestibule, Labyrinth
PubMed: 30699041
DOI: 10.1152/jn.00674.2018 -
Molecules (Basel, Switzerland) Jan 2020Baclofen is a racemic mixture that is commonly used for the treatment for spasticity. However, the optimal dose and dosing interval to achieve effective cerebral spinal...
Baclofen is a racemic mixture that is commonly used for the treatment for spasticity. However, the optimal dose and dosing interval to achieve effective cerebral spinal fluid (CSF) concentrations of baclofen are not known. Moreover, it is unclear if there are differences in the ability of R- or S-baclofen to cross the blood-brain barrier and achieve effective CSF concentrations. We have validated a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method with improved selectivity and sensitivity for the simultaneous quantitation of R- and S-baclofen and metabolites in plasma and CSF. Protein precipitation by acetonitrile was utilized to obtain an acceptable recovery of the analytes. The detection and separation of analytes was achieved on a 48 °C-heated Crownpak CR(+) column (150 mm × 4.0 mm, 5μ) with elution using 0.4% formic acid (FA) in water and 0.4% FA in acetonitrile as the mobile phase running at a flow rate of 1.0 mL/min. Accurate quantitation was assured by using this MS/MS method with atmospheric pressure chemical ionization in multiple reaction monitoring (MRM) mode. Therefore, this method is enantioselective, accurate, precise, sensitive, reliable, and linear from 1 to 1500 ng/mL for baclofen and 2 to 4000 ng/mL for the metabolites. An additional method was developed to separate racemic baclofen 3-(4-chlorophenyl)-4 hydroxybutyric acid metabolites for individual concentration determination. Both validated methods were successfully applied to a clinical pharmacokinetic human plasma and CSF study evaluating the disposition of baclofen and metabolites.
Topics: Atmospheric Pressure; Baclofen; Calibration; Chromatography, Liquid; Drug Monitoring; Female; Humans; Male; Metabolome; Stereoisomerism; Tandem Mass Spectrometry; Young Adult
PubMed: 31936209
DOI: 10.3390/molecules25020250 -
BMC Urology Oct 2021Baclofen, a clinically available GABA receptor agonist, produces non-opioid analgesia in multiple models of pain but has not been tested for effects on bladder...
BACKGROUND
Baclofen, a clinically available GABA receptor agonist, produces non-opioid analgesia in multiple models of pain but has not been tested for effects on bladder nociception.
METHODS
A series of experiments examined the effects of systemic and spinally administered baclofen on bladder nociception in female anesthetized rats. Models of bladder nociception included those which employed neonatal and adult bladder inflammation to produce bladder hypersensitivity.
RESULTS
Cumulative intraperitoneal dosing (1-8 mg/kg IP) and cumulative intrathecal dosing (10-160 ng IT) of baclofen led to dose-dependent inhibition of visceromotor responses (VMRs) to urinary bladder distension (UBD) in all tested models. There were no differences in the magnitude of the analgesic effects of baclofen as a function of inflammation versus no inflammation treatments. Hemodynamic (pressor) responses to UBD were similarly inhibited by IT baclofen as well as UBD-evoked excitatory responses of spinal dorsal horn neurons. The GABA receptor antagonist, CGP 35,348, antagonized the antinociceptive effects of IT baclofen on VMRs in all tested models but did not affect the magnitude of the VMRs by itself suggesting no tonic GABA activity was present in this preparation. Tolerance to a seven day continuous IT infusion of baclofen was not observed.
CONCLUSIONS
These data provide support for a clinical trial of baclofen as a non-opioid treatment of human bladder pain.
Topics: Animals; Baclofen; Female; GABA-B Receptor Agonists; Injections, Spinal; Nociception; Rats; Rats, Sprague-Dawley; Urinary Bladder
PubMed: 34607587
DOI: 10.1186/s12894-021-00899-0 -
Drug Design, Development and Therapy 2021This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis. (Comparative Study)
Comparative Study
Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method.
PURPOSE
This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis.
METHODS
Direct compression method was used to prepare ODTs using three types of co-processed excipients (Prosolv ODT G2, F-melt, and Pharmaburst500). ODTs were evaluated according to weight variation, thickness, friability, hardness, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution test, and palatability. To enhance the in-vitro dissolution of meloxicam and palatability of ODT, a six sigma methodology was used, and an improvement phase was established where ODTs were prepared using lyophilization and levigation techniques. Finally, a pharmacokinetic study of the improved ODT was accomplished in comparison to the conventional oral tablet.
RESULTS
Pharmaburst-based formula (F4) showed the shortest wetting time and, consequently, the shortest disintegration time and the highest percentage of drug dissolved within 3 min compared to the other formulae. All the improved ODTs had a bitterness taste score vary from (0) palatable and (+1) tasteless. The current sigma level was 3.628 σ and 3.33 σ for palatability and solubility of ODT, respectively, which indicated the process was successfully improved compared with the previous sigma level of 2.342 σ of both processes. Pharmacokinetic study of the improved ODTs showed a significant decrease of T to 120 and 30 min instead of 180 and 120 min for meloxicam and baclofen, respectively.
CONCLUSION
ODTs were successfully improved using the six sigma methodology, the pharmacokinetic parameters of both drugs were enhanced due to rapid absorption through the oral mucosa.
Topics: Administration, Oral; Adult; Baclofen; Drug Compounding; Drug Liberation; Excipients; Female; Freeze Drying; Humans; Male; Meloxicam; Muscle Relaxants, Central; Solubility; Tablets; Taste; Total Quality Management
PubMed: 34690500
DOI: 10.2147/DDDT.S327193 -
Alimentary Pharmacology & Therapeutics Dec 2014
Topics: Baclofen; Esophageal Sphincter, Lower; Female; GABA-B Receptor Agonists; Gastroesophageal Reflux; Humans; Male; Stomach
PubMed: 25376198
DOI: 10.1111/apt.12987 -
The Journal of Clinical Psychiatry Aug 2020Alcohol use disorders (AUD) are common and impairing. Many pharmacologic interventions have been approved for AUD; baclofen is one among these. More than a dozen... (Review)
Review
Alcohol use disorders (AUD) are common and impairing. Many pharmacologic interventions have been approved for AUD; baclofen is one among these. More than a dozen randomized controlled trials (RCTs) have examined the safety and efficacy of baclofen in AUD; these RCTs have been pooled in 4 recent meta-analyses, each with different study selection criteria, different objectives, different methods, and different results. The general impression from these meta-analyses is that the benefits with baclofen are unimpressive in patients with AUD. With the background that individualized, rather than fixed, high dosing with baclofen could be critical for success, a large (n = 320), industry-independent, 62-center French RCT (the Bacloville trial) examined whether individually uptitrated, high-dose baclofen could reduce alcohol consumption in heavy drinkers across a year of treatment. The study design, the high dropout rate, and the statistical methods of this trial threw up several complexities; in consequence, the main primary and secondary outcomes could not be satisfactorily interpreted. However, there were many other secondary outcomes that seemed to favor baclofen over placebo, though certain concerns remained. This RCT is explained and its findings are carefully dissected and interpreted. It is concluded that individualized treatment with high-dose baclofen (30-300 mg/d) may be a useful second-line approach in heavy drinkers who wish to reduce levels of alcohol intake; baclofen may be particularly useful in patients with liver disease, for whom certain other pharmacologic interventions are relatively contraindicated. However, the risk of serious adverse events with high-dose baclofen, and its pharmacodynamic interaction with alcohol, must both be kept in mind. Practical issues are discussed.
Topics: Alcohol Drinking; Alcoholism; Baclofen; GABA-B Receptor Agonists; Humans; Meta-Analysis as Topic
PubMed: 32757504
DOI: 10.4088/JCP.20f13606