Gabapentinoids, including gabapentin and pregabalin are medications used to treat seizures, anxiety and pain caused by nerve damage. Recently, their prescription has increased in North America and Europe, partly due to use for unapproved indications. However, these medications are ineffective for many unapproved uses and can cause serious adverse effects, including sleepiness and respiratory problems. Breathing difficulties have been reported in some patients using gabapentinoids, raising concerns for those with respiratory diseases like chronic obstructive pulmonary disease (COPD), who are at higher risk. Several health agencies have warned about the potential respiratory risks associated with gabapentinoids, especially in patients with COPD. However, there is no population-based study investigating these effects in patients with COPD. Thus, the main objective of our study is to assess whether gabapentinoid use is associated with severe COPD episodes among patients with COPD. We will form two groups of patients with COPD, one group comprising gabapentinoid users and the other group with non-users. We will compare the number of patients who have severe COPD episodes during follow-up among gabapentinoids users versus non-users. We will also study the difference according to the duration of use, age, sex, and COPD severity. This study will provide important information to guide gabapentinoid use in patients with COPD.
Gabapentinoids are indicated for the treatment of epilepsy, neuropathic pain and generalized anxiety disorder. Despite surging off-label use in Europe and North America, gabapentinoids are ineffective for many off-label indications while posing potentially severe adverse effects like central nervous system (CNS) depression, sedation, and respiratory depression. Case reports and prior studies have also reported severe respiratory difficulties associated with gabapentinoid use. Patients with COPD are of specific concern due to their increased susceptibility to adverse respiratory events amid the high prevalence of pain-related diagnoses and frequent analgesic use in this population. Regulatory agencies have issued warnings about the potential respiratory risks associated with gabapentinoids, especially in patients with COPD, yet no population-based study has investigated gabapentinoid-related respiratory adverse effects in this population. We will conduct a population-based cohort study to assess whether gabapentinoid use is associated with severe exacerbation among patients with COPD. Within a base cohort of all patients in the CPRD, newly diagnosed with COPD between 1993 and 2021, we will identify patients initiating gabapentinoids during follow-up, matched 1:1 on time-conditional propensity scores to non-users. Using the Poisson distribution, we will estimate crude incidence rates and 95% confidence intervals (CIs) for severe COPD exacerbation in each exposure group. We will use Cox proportional hazards models to estimate the hazard ratio and 95% CI for severe exacerbation associated with gabapentinoid use versus non-use. In secondary analyses, we will assess whether the risk varies with the duration of gabapentinoid use, age, sex, and COPD severity. Sensitivity analyses will be performed to assess the robustness of our results.
The primary outcome will be severe COPD exacerbation.
The secondary outcome will be respiratory failure.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Omotayo Olaoye - Collaborator - McGill University
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation