The French pharmacovigilance system is based on a decentralized collection and validation of safety data through a network of 31 regional pharmacovigilance centers and a centralized evaluation and decision-making process coordinated by the French National Agency for the Safety of Medicines and Health Products (ANSM). This organization enables ANSM to ensure the safe use of medicinal products after marketing with the objective to protect public health in France.
Introduction & Background: Due to the structural similarity between gabapentin and baclofen, gabapentin was reported to produce ‘baclofen-like’ effects. Baclofen is linked to sleep apnea syndrome (SAS), aggravating sleep-disordered breathing by depressing central ventilatory drive and/or increasing upper airway obstruction. Aims & Objectives: We hypothesized that gabapentinoids might be associated with SAS. Methods: We performed a disproportionality analysis within Vigibase, the large WHO pharmacovigilance database. The relationship between the use of each antiepileptic and the occurrence of adverse drug reaction (i.e. SAS) was assessed by calculating the reported odds ratio (ROR) [95% confidence intervals] in a case-noncase model. Results: Of the 17 519 277 Individual Case Safety Reports reported to Vigibase between December 1970 and July 2018, 8915 (0.05%) were SAS cases; 76 cases of SAS for gabapentin and 123 for pregabalin. The ROR for both drugs were significant: 2.61 [2.08 to 3.27] for gabapentin and 2.42 [2.02 to 2.89] for pregabalin, whereas no other antiepileptic drugs had a ROR with lower boundary > 2. The ROR was also significant for benzodiazepines: 3.07 [2.58 to 3.66] (Figure 1). Conclusions: Rates of gabapentinoids use in the USA tripled between 2002 and 2015, especially in opioid crisis context leading to the emergence of pregabalin and gabapentin misuse and abuse. Physicians need to be aware that sleep apnea might affect patients treated with gabapentinoids.
Baclofen is a centrally acting gamma aminobutyric acid (GABA)-B agonist, widely used for chronic spasticity in neurological disorders, available in oral and intrathecal formulations. Depending on the severity of spasticity and tolerance, standard treatment includes daily oral administration of 40–80 mg [1]. The main adverse effects reported with baclofen are sedation, sleepiness, weakness, dizziness and psychological disturbances [2]. According to the depressant effects of GABA on the central nervous system, baclofen might also induce or aggravate sleep-disordered breathing by depressing central ventilatory drive and/or increasing upper airway obstruction. A single oral low dose of baclofen did not significantly impair the apnoea–hypopnoea index (AHI) in a population with moderate obstructive sleep apnoea [3], but bolus intrathecal administration of the drug increased central sleep apnoea (CSA) in patients with severe spasticity [4]. Baclofen is associated with sleep apnoea syndrome especially the high oral doses prescribed for alcohol addiction The authors would like to thank the UMC that provided and gave permission to use the data analysed in the present study. Results and conclusions are those of the authors and not necessarily those of the National Centers, UMC or WHO. We thank Alison Foote (Grenoble Alps University Hospital, France) for critically editing the manuscript.
