Toxicological considerations in the prescription of baclofen for the treatment of substance use disorders

Reynoard, Julien; Schmitt, C.; Torrents, Romain; Simon, Nicolas

doi:10.1080/17425255.2020.1740681

Cited by 4 publications

(5 citation statements)

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“…Acamprosate and baclofen are both renally cleared and caution is advised in renal failure [13,25]. In our cohort, few patients had evidence of kidney disease or hepatorenal syndrome.…”

Section: Resultsmentioning

confidence: 99%

“…Given the limitations of this retrospective audit, the higher rate of admissions observed cannot be inferred to have been caused by baclofen use, but we did note an increased number of admissions attributed to hepatic encephalopathy or confusion in patients taking baclofen in contrast to those taking acamprosate – albeit this did not reach significance. Concomitant alcohol use is a historical concern in patients treated with baclofen off-label for AUD as it is felt to increase the risk of sedation and overdose [13,28]. Furthermore, a higher rate of hospitalisation has previously been seen in otherwise healthy patients without liver disease treated with baclofen for AUD, in contrast to those treated with medications such as acamprosate [16].…”

Section: Discussionmentioning

confidence: 99%

“…Aside from efficacy, there are concerns about the safety of baclofen, especially at high dose [13]. Clinical trials using high doses of baclofen (titrated to 150–300 mg total dose per day) have reported more frequent side effects [14] and serious adverse events [15] in the treatment arms, with only modest [15] or insignificant [14] benefits.…”

Section: Introductionmentioning

confidence: 99%

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Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice

Tyson

Cheng

Kelleher

et al. 2021

European Journal of Gastroenterology &Amp; Hepatology

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Objectives Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients. Methods The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression. Results In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Subgroup analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed. Conclusions In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns.

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“…Acamprosate and baclofen are both renally cleared and caution is advised in renal failure [13,25]. In our cohort, few patients had evidence of kidney disease or hepatorenal syndrome.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice

Tyson

Cheng

Kelleher

et al. 2021

European Journal of Gastroenterology &Amp; Hepatology

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“…Intrathecal Baclofen is an effective and safe long-term treatment used worldwide to treat severe spasticity [ 50 , 51 ]. Oral baclofen is less effective and has significant rates of side effects, like sedation, somnolence, vertigo and headache especially when prescribed off-label for drug addiction (because higher doses are commonly used) [ 51 , 52 ] . .…”

Section: Converging Actions On Brain Reward Pathway Elicit Its Remodellingmentioning

confidence: 99%

“…Thus, self-poisoning that could lead to severe toxicity and death represents one the major concern of baclofen use in drug addiction. Therefore, baclofen should be prescribed with caution and close monitoring [ 52 , 57 ].…”

Section: Converging Actions On Brain Reward Pathway Elicit Its Remodellingmentioning

confidence: 99%

Drug addiction: from bench to bedside

Cheron

d’Exaerde

2021

Transl Psychiatry

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Drug addiction is responsible for millions of deaths per year around the world. Still, its management as a chronic disease is shadowed by misconceptions from the general public. Indeed, drug consumers are often labelled as “weak”, “immoral” or “depraved”. Consequently, drug addiction is often perceived as an individual problem and not societal. In technical terms, drug addiction is defined as a chronic, relapsing disease resulting from sustained effects of drugs on the brain. Through a better characterisation of the cerebral circuits involved, and the long-term modifications of the brain induced by addictive drugs administrations, first, we might be able to change the way the general public see the patient who is suffering from drug addiction, and second, we might be able to find new treatments to normalise the altered brain homeostasis. In this review, we synthetise the contribution of fundamental research to the understanding drug addiction and its contribution to potential novel therapeutics. Mostly based on drug-induced modifications of synaptic plasticity and epigenetic mechanisms (and their behavioural correlates) and after demonstration of their reversibility, we tried to highlight promising therapeutics. We also underline the specific temporal dynamics and psychosocial aspects of this complex psychiatric disease adding parameters to be considered in clinical trials and paving the way to test new therapeutic venues.

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