Severe Central Sleep Apnea Associated With Chronic Baclofen Therapy

Abstract

Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage.

Risk of hospitalisation and death related to baclofen for alcohol use disorders: Comparison with nalmefene, acamprosate, and naltrexone in a cohort study of 165 334 patients between 2009 and 2015 in France

“…Retrospective data from French poison centres, published by Pélissier (2017), included 294 cases of poisoning with baclofen between 2008 and 2013, including nine deaths, particularly in the context of suicide, and cardiorespiratory phenomena at high doses . In 2016, Olivier reported four cases of severe central sleep apnoea in the absence of the other risk factors commonly associated with this disease …”

“…and several serious adverse reactions have been reported by the French pharmacovigilance network and case reports. [19][20][21] These studies were not designed to assess the safety of baclofen in terms of all-cause hospitalisation and death, particularly at doses much higher than those recommended for the approved indication. 22,23 This study was conducted to evaluate the risk of hospitalisation and death (specific and all-cause) of real-life use of baclofen compared to the main approved drugs for AUD.…”

Review article: pharmacotherapy for alcohol dependence – the why, the what and the wherefore

“…Fatigue, sleep disorders and vertigo/dizziness were more frequent in those taking the active drug particularly in the high‐dose studies. Reports of further adverse event such as major sedation, seizures, mania and sleep apnoea are increasing in parallel with increased use of this drug.…”

Valproic acid and sleep apnoea: A disproportionality signal from the WHO pharmacovigilance database

“…4 Owing to structural similarities, gabapentinoids can induce a 'baclofen-like' effect on respiratory centres, leading to central sleep apnoea (CSA) characterized by a lack of respiratory drive during sleep. 5,6 CSA has been recently reported in two patients treated with valproic acid. 7 These two cases were confirmed by sleep polysomnography, suggesting a potential causal role of valproic acid in inducing CSA.…”

“…Despite this potential methodological issue, we found a significant disproportionality signal. Recently, our group highlighted the increased risk of sleep apnoea associated with the centrally acting GABA-B agonist baclofen 5,6 and with second-generation antiepileptic drugs gabapentinoids. 3 Both gabapentinoids and valproic acid elevate GABA levels in the central nervous system and might depress central ventilatory drive, in line with our initial pharmacological hypothesis.…”