Gabapentinoids and sleep apnea syndrome: a safety signal from the WHO pharmacovigilance database.

Abstract

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.