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Biological Approaches
Published in Tricia L. Chandler, Fredrick Dombrowski, Tara G. Matthews, Co-occurring Mental Illness and Substance Use Disorders, 2022
Tricia L. Chandler, Mary C. Hoke, Tara G. Matthews, Elizabeth Reyes-Fournier
Baclofen is a gamma-aminobutyric acid (GABA) agonist primarily used as a skeletal muscle relaxant for the relief of painful and uncomfortable muscle spasms caused by a variety of conditions. Baclofen has more recently been studied for the management of alcohol withdrawal; however, a conclusion has not been made regarding Baclofen efficacy for this condition. The pharmacodynamics of Baclofen with GABA-B receptor activation produce neurological effects, including anti-inflammatory properties of interest in addiction treatment. Studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, and anxiety. Neuroimaging studies in humans indicate that Baclofen produces region-specific alterations in brain activity. Because Baclofen is partially metabolized in the liver, patients with impaired liver function should be regularly monitored with liver function tests. Baclofen is excreted mainly by the kidney as an unchanged drug. The half-life is 5.5 hours (Fu et al., 2012).
Systemic, Intrathecal, and Intravesical Pharmacologic Treatment of Neurogenic Lower Urinary Tract Dysfunction
Published in Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg, Essentials of the Adult Neurogenic Bladder, 2020
To date, the most commonly studied intrathecal therapy for NLUTD has been carried out in patients with baclofen pumps. Baclofen is thought to inhibit spinal cord transmission via its activation of γ-aminobutyric acid (GABA) receptors. In those with neurologic disability, baclofen is used primarily to control skeletal muscle spasticity.19 A noted concurrent effect is a decrease in external striated sphincter activity, which allows some patients, whose prior spasticity prevented catheter passage, to perform intermittent catheterization with greater ease.20 Unfortunately, however, the practical use of baclofen to decrease bladder outlet resistance and promote volitional voiding in those with detrusor-sphincter dyssynergia is limited by the concurrent side effects of ever-increasing doses (i.e., drowsiness and weakness) and is not of practical use.21
Overview of Neurotransmission: Relationship to the Action of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
While it is clear that the GABAA agonists are effective anticonvulsant compounds, the value of GABAB agonists as anticonvulsants is less clear. For example, while (-) baclofen has been shown to suppress seizures in several experimental models of epilepsy, its value in humans is questionable.100 However, recent studies suggest that a more careful examination of the effects of baclofen on seizures in children may be warranted.101
Clinical assessment, management, and rehabilitation of walking impairment in MS: an expert review
Published in Expert Review of Neurotherapeutics, 2020
Bernardita Soler, Cintia Ramari, Maxime Valet, Ulrik Dalgas, Peter Feys
Gait dysfunction that is primarily a result of lower limb spasticity may be treated with medication like Baclofen, which is a derivative of γ aminobutyric acid (GABA) and it is a GABA B receptor and glycine receptor agonist that acts at spinal and supraspinal sites. The side effects of oral baclofen are dizziness, weakness, fatigue, and seizures. It is generally effective and tolerated. When spasticity is severe or the oral treatment dose is not tolerated, but control of spasticity could improve function and quality of life, intrathecal baclofen pump may be recommended. Intrathecal baclofen is administered by a programmable, subcutaneously implanted drug delivery system with a reservoir and catheter, delivering low doses of baclofen (<1% of the oral dose) [59], directly to the spinal cord. Intrathecal baclofen therapy should be considered when spasticity is inadequately managed by other treatments or side effects of such are unacceptable.
Effect of oral baclofen on spasticity poststroke: responders versus non-responders
Published in Topics in Stroke Rehabilitation, 2018
Shiho Mizuno, Kotaro Takeda, Shinichiro Maeshima, Sonoda Shigeru
Previously, Chu et al. investigated ankle torque and the activity of the gastrocnemius during the hold period, after passive fast stretch in 10 participants with spinal cord injuries. The authors concluded that reduced stretch reflex activity was observed after a single dose of baclofen at 30 mg.12 Hinderer et al. compared the degree of viscoelastic stiffness after the oral administration of baclofen (40 and 80 mg/day) and after placebo administration in five adults with traumatic spinal cord injuries. Oral administration of baclofen caused no change in stiffness, suggesting that baclofen is not a universal treatment of choice for all patients with spasticity resulting from a spinal cord injury.13 Furthermore, the effect of baclofen on spasticity in persons poststroke remains unknown.
N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research
Published in Expert Opinion on Investigational Drugs, 2018
Kirsten C. Morley, Andrew Baillie, Wim Van Den Brink, Kate E. Chitty, Kathleen Brady, Sudie E. Back, Devanshi Seth, Greg Sutherland, Lorenzo Leggio, Paul S. Haber
Baclofen has emerged as popular pharmacotherapy and while results are somewhat mixed, a recent metaanalysis has reported some efficacy, particularly in patients with higher levels of alcohol consumption before randomization [13]. There have been only two formal placebo-controlled studies of an alcohol pharmacotherapy in patients specifically diagnosed with ALD and both of these trials demonstrated efficacy of baclofen at low to medium doses 30–75 mg/day [14,15]. Some studies have observed an adverse event profile including fatigue, sleepiness, and sedation in medium to higher doses 75–150 mg/day [14,16]. It is important to note the risk of overdose following deliberate self-poisoning with baclofen [14,17]. This can be a concern in the case of comorbid psychiatric conditions such as bipolar or borderline personality disorder [18,19]. Since the emergence of interest in baclofen there have been increased reports to poison control agencies both in Australia [17] and France [20]. This uncertain harm-benefit balance arguably precludes widespread use of baclofen in the community whereby it is not recommended for patients with mood disorders or risk of deliberate self-poisoning. Accordingly, there are few safe and effective medications aimed at reducing alcohol consumption for ALD patients that can be widely prescribed.