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BMJ Case Reports May 2017Baclofen is a new and promising pharmacological compound for the treatment of alcohol dependence (AD). Although several randomised trials found a reduction of craving...
Baclofen is a new and promising pharmacological compound for the treatment of alcohol dependence (AD). Although several randomised trials found a reduction of craving and higher abstinence rates with low and high doses of baclofen, others failed to show positive effects. In this case study, the successful treatment of a patient with AD with daily 120 mg of baclofen is described. In addition to a decrease in alcohol use, we observed the cessation of stuttering during treatment with baclofen, reoccurrence of stuttering following discontinuation, and cessation of stuttering after reinstatement of the treatment. Based on this observation, the direct effects of baclofen on muscle relaxation and anxiety reduction and its indirect effect on dopaminergic inhibition, we believe that baclofen might be a new treatment for stuttering. Further research into the effect of baclofen on stuttering is warranted.
Topics: Alcohol Abstinence; Alcohol Drinking; Alcoholism; Anxiety; Baclofen; GABA-B Receptor Agonists; Humans; Male; Middle Aged; Netherlands; Randomized Controlled Trials as Topic; Stuttering; Treatment Outcome
PubMed: 28495786
DOI: 10.1136/bcr-2016-218714 -
Journal of the Formosan Medical... Apr 2011Spasticity is a common disability in children with cerebral palsy. Pharmacological and non-pharmacological treatments, including physical therapy, occupational therapy,... (Review)
Review
Spasticity is a common disability in children with cerebral palsy. Pharmacological and non-pharmacological treatments, including physical therapy, occupational therapy, orthotics, rhizotomy, and orthopedic surgery, all play important roles in the management of spasticity. The purpose of this article is to provide an overview of available medications for treatment of spasticity in children with cerebral palsy. Common medications include benzodiazepines, dantrolene sodium, baclofen, tizanidine, botulinum toxins, phenol, alcohol and intrathecal baclofen. In general, oral medications and intrathecal baclofen are used for treating generalized spasticity, whilst chemodenervation agents (botulinum toxins, phenol, and alcohol) are used to treat localized spasticity. There is more sufficient evidence for the recommendation of botulinum toxin A as an effective anti-spasticity treatment in children with cerebral palsy. However, more data concerning safety and long-term effects of botulinum toxin A is needed. Further study is needed to determine which kinds of medications can cause substantial improvement in daily activity, participation level, self-competence, or quality of life in children with cerebral palsy.
Topics: Baclofen; Benzodiazepines; Cerebral Palsy; Child; Clonidine; Dantrolene; Humans; Muscle Spasticity; Neuromuscular Blocking Agents
PubMed: 21540003
DOI: 10.1016/S0929-6646(11)60033-8 -
Alcohol (Fayetteville, N.Y.) Sep 2022Baclofen is a GABA receptor agonist with proposed use as a treatment for alcohol use disorder (AUD). In preclinical studies, racemic baclofen decreases alcohol...
Baclofen is a GABA receptor agonist with proposed use as a treatment for alcohol use disorder (AUD). In preclinical studies, racemic baclofen decreases alcohol consumption in both mice and rats; however, there is a significant disparity in the efficacy of the drug across species. We previously demonstrated that baclofen is enantioselective, with the racemic enantiomer successfully reducing binge-like alcohol consumption during Drinking-in-the-Dark (DID) in C57BL/6J (B6) mice, as well as 24-h consumption during two-bottle choice (2BC) preference drinking in replicate 1 High Alcohol Preferring (HAP) mice. Here we extend these findings by investigating the effects of racemic baclofen on the acquisition and maintenance of alcohol consumption, locomotor activity, and saccharin drinking in two different mouse genotypes and drinking paradigms. Adult male and female B6 mice were allowed free access to 20% (v/v) alcohol for 2 h daily in a 14-day DID procedure. Adult male and female replicate 2 HAP (HAP2) mice were allowed 24-h access to 10% (v/v) alcohol versus tap water in a 2BC procedure for 14 days. Systemic injections of baclofen (0.0 or 3.0 mg/kg) were given 3 h into the dark cycle on days 1-5 in alcohol acquisition experiments and days 6-10 in alcohol maintenance experiments. We found that racemic baclofen significantly reduces acquisition of DID and 2BC alcohol drinking in male and female B6 and HAP2 mice, whereas it only significantly reduces the maintenance of DID alcohol intake in B6 mice. Racemic baclofen did not alter home cage locomotor activity but did alter saccharin intake, suggesting it may have nonspecific effects. The current data add to literature suggesting that smaller doses of racemic baclofen may be an effective treatment of AUD. Future work should focus on the longitudinal efficacy of racemic baclofen in high-drinking mouse genotypes to further investigate whether it is effective for those with a genetic predisposition to AUD.
Topics: Alcohol Drinking; Alcoholism; Animals; Baclofen; Ethanol; Female; GABA-B Receptor Agonists; Male; Mice; Mice, Inbred C57BL; Rats; Saccharin; Water
PubMed: 35870740
DOI: 10.1016/j.alcohol.2022.06.003 -
The Journal of Clinical Psychiatry Jan 2021
Topics: Alcohol Drinking; Baclofen; Humans
PubMed: 33434960
DOI: 10.4088/JCP.20lr13642a -
Behavioural Pharmacology Apr 2021In humans, there is profound individual variation in the risk of alcohol use disorder (AUD). Because GABA, opioid and glutamate neurotransmission have been implicated in... (Comparative Study)
Comparative Study
In humans, there is profound individual variation in the risk of alcohol use disorder (AUD). Because GABA, opioid and glutamate neurotransmission have been implicated in AUD, functional differences in these neural systems may underlie the individual vulnerability to AUD. We therefore determined the effects of drugs affecting GABA, opioid and glutamatergic neurotransmission on alcohol consumption in rats that differed in baseline alcohol intake. Subgroups of low-, medium- and high-alcohol-drinking rats were selected on the basis of alcohol consumption using an intermittent alcohol access procedure. The subgroups were treated with the GABAB receptor agonist baclofen, the opioid receptor antagonist naltrexone and the cysteine precursor N-acetylcysteine, and the effects on alcohol intake and preference were determined. Both baclofen and naltrexone reduced alcohol consumption, but N-acetylcysteine did not. These effects were comparable for low-, medium- and high-alcohol-drinking rats. However, there was a substantial degree of individual variation in the responsivity to baclofen and naltrexone, across the subgroups. Taken together, these results suggest that variation in alcohol consumption does not predict the responsivity to baclofen and naltrexone. This implies that individual variability in alcohol consumption on the one hand and sensitivity to treatment with these drugs on the other hand represent separate processes that likely involve distinct biological mechanisms.
Topics: Acetylcysteine; Alcohol Drinking; Animals; Baclofen; Ethanol; GABA-B Receptor Agonists; Male; Naltrexone; Narcotic Antagonists; Rats
PubMed: 33315615
DOI: 10.1097/FBP.0000000000000615 -
Developmental Medicine and Child... Apr 2018To systematically review evidence for pharmacological/neurosurgical interventions for managing dystonia in individuals with cerebral palsy (CP) to inform a care pathway. (Review)
Review
AIM
To systematically review evidence for pharmacological/neurosurgical interventions for managing dystonia in individuals with cerebral palsy (CP) to inform a care pathway.
METHOD
Searches included studies with a minimum of five participants with dystonia in CP receiving oral baclofen, benzodiazepines (clonazepam, diazepam, lorazepam), clonidine, gabapentin, levodopa, trihexyphenidyl, botulinum toxin, intrathecal baclofen (ITB), or deep brain stimulation (DBS). Evidence was classified according to American Academy of Neurology guidelines.
RESULTS
Twenty-eight articles underwent data extraction: one levodopa, five trihexyphenidyl, three botulinum toxin, six ITB, and 13 DBS studies. No articles for oral baclofen, benzodiazepines, clonidine, or gabapentin met the inclusion criteria. Evidence for reducing dystonia was level C (possibly effective) for ITB and DBS; level C (possibly ineffective) for trihexyphenidyl; and level U (inadequate data) for botulinum toxin.
INTERPRETATION
For dystonia reduction, ITB and DBS are possibly effective, whereas trihexyphenidyl was possibly ineffective. There is insufficient evidence to support oral medications or botulinum toxin to reduce dystonia. There is insufficient evidence for pharmacological and neurosurgical interventions to improve motor function, decrease pain, and ease caregiving. The majority of the pharmacological and neurosurgical management of dystonia in CP is based on clinical expert opinion.
WHAT THIS PAPER ADDS
Intrathecal baclofen and deep brain stimulation are possibly effective in reducing dystonia. Current evidence does not support effectiveness of oral medications or botulinum toxin to reduce dystonia. Evidence is inadequate for pharmacological/neurosurgical interventions impact on improving motor function, pain/comfort, and easing caregiving. The majority of the care pathway rests on expert opinion.
Topics: Baclofen; Cerebral Palsy; Deep Brain Stimulation; Dystonia; Humans; Muscle Relaxants, Central; Neurosurgical Procedures
PubMed: 29405267
DOI: 10.1111/dmcn.13652 -
Developmental Medicine and Child... Jul 2010
Topics: Baclofen; Cerebral Palsy; Humans; Infusion Pumps, Implantable; Injections, Spinal; Muscle Hypertonia; Muscle Relaxants, Central; Patient Selection
PubMed: 19832881
DOI: 10.1111/j.1469-8749.2009.03515.x -
Neuropsychopharmacology : Official... Dec 2021Identification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABA agonist, has been identified as a... (Randomized Controlled Trial)
Randomized Controlled Trial
Identification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABA agonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90 mg/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd = 10.1) years, 51.7% male) were randomized after exclusion for unstable medical/psychiatric illness and/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112) = 4.16, p = 0.018, d = 0.51 95%CI (0.06-0.95), 13.6 fewer HDD) and %ABST (F(2,112) = 3.68, p = 0.028, d = 0.49 95%CI (0.04-0.93), 12.9 more abstinent days)] and was driven by the 90 mg/day dose. A sex × dose interaction effect was present for both %HDD (F(2,110) = 5.48, p = 0.005) and %ABST (F(2,110) = 3.19, p = 0.045). Men showed a marginally positive effect for 90 mg/day compared to PBO (%HDD t(110) = 1.88, p = 0.063, d = 0.36 95%CI (-0.09-0.80), 15.8 fewer HDD days; %ABST t(110) = 1.68 (p = 0.096, d = 0.32 95%CI (-0.12-0.76), 15.7 more ABST)) with no effect for 30 mg/day. Women showed a positive effect for 30 mg/day (%HDD, t(110) = 3.19, p = 0.002, d = 0.61 95%CI (0.16-1.05), 26.3 fewer HDD days; %ABST t(110) = 2.73, p = 0.007, d = 0.52 95%CI (0.07-0.96), 25.4 more ABST days) with marginal effects for 90 mg/day on %ABST (p = 0.06) with drop-outs/dose reduction from sedative side-effects of 59% in women at 90 mg/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.
Topics: Alcoholism; Baclofen; Double-Blind Method; Female; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 34155332
DOI: 10.1038/s41386-021-01055-w -
Alimentary Pharmacology & Therapeutics Dec 2014
Topics: Baclofen; Esophageal Sphincter, Lower; Female; GABA-B Receptor Agonists; Gastroesophageal Reflux; Humans; Male; Stomach
PubMed: 25376199
DOI: 10.1111/apt.12996 -
Neuroscience Apr 2019The aims of the study were to compare effects of baclofen, a GABA receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting...
The aims of the study were to compare effects of baclofen, a GABA receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting changes in the excitability of afferent fibers traversing the dorsal columns and their terminal branches in the spinal cord, and to examine whether baclofen interferes with the development and expression of these changes. The experiments were performed on deeply anesthetized rats by analyzing the effects of DC before, during and following baclofen administration. Muscle and skin afferent fibers within the dorsal columns were stimulated epidurally and changes in their excitability were investigated following epidural polarization by 1.0-1.1 μA subsequent to i.v. administration of baclofen. Epidural polarization increased the excitability of these fibers during post-polarization periods of at least 1 h. The facilitation was as potent as in preparations that were not pretreated with baclofen, indicating that the advantages of combining epidural polarization with epidural stimulation would not be endangered by pharmacological antispastic treatment with baclofen. In contrast, baclofen-reduced effects of intraspinal stimulation combined with intraspinal polarization (0.3 μA) of terminal axonal branches of the afferents within the dorsal horn or in motor nuclei, whether administered ionophoretically or intravenously. Effects of DC on monosynaptically evoked synaptic actions of these fibers (extracellular field potentials) were likewise reduced by baclofen. The study thus provides further evidence for differential effects of DC on afferent fibers in the dorsal columns and the preterminal branches of these fibers and their involvement in spinal plasticity.
Topics: Animals; Baclofen; Electric Stimulation; Female; GABA-B Receptor Agonists; Male; Neuronal Plasticity; Neurons, Afferent; Rats; Rats, Wistar; Spinal Cord
PubMed: 30710669
DOI: 10.1016/j.neuroscience.2019.01.047