A recent population-based cohort study conducted in Canada has revealed a concerning link between the use of gabapentinoids and an increased risk of severe exacerbations in patients with chronic obstructive pulmonary disease (COPD). The study, led by Christel Renoux, MD, PhD, of the Lady Davis Institute and Jewish General Hospital in Montreal, analyzed data from over 27,000 COPD patients and found that those who initiated treatment with gabapentinoids for conditions such as epilepsy, neuropathic pain, or other chronic pain had a 39% higher risk of experiencing severe exacerbations compared to a matched group of non-users. These findings cut across various demographic variables, including age, sex, and severity of COPD. The increased risk was consistent among the three subgroups studied: epilepsy, neuropathic pain, and other chronic pain.
Implications for Clinical Practice and Guidelines
The study’s findings have significant implications for clinical practice and the management of patients with COPD. While public health agencies have warned of the potential respiratory depression associated with gabapentinoids, this information has not yet been adequately reflected in clinical practice guidelines for COPD and neuropathic pain. Many guidelines still recommend gabapentinoids as first-line pharmacotherapeutic options for managing neuropathic pain. However, this study suggests that healthcare professionals should exercise caution when prescribing gabapentinoids to COPD patients. By shedding light on the increased risk of severe exacerbations, this research may help inform the appropriate and safe use of gabapentinoids in this patient population.
The rising use of gabapentinoids, both on and off-label, in North America is concerning, particularly in the context of the opioid epidemic. These drugs are often perceived as a safer alternative to opioids, leading to their increasing prescription rates. However, the study emphasizes that gabapentinoids have limited effectiveness in many off-label indications, despite exposing patients to potentially serious adverse effects. Central nervous system depression, resulting in sedation and respiratory depression, has been reported in both animal and human studies. It is essential to consider the risks associated with gabapentinoid use and evaluate their benefits carefully, especially in patients with COPD.
To conduct the study, Renoux and colleagues utilized three digital health insurance databases in Quebec and included 13,504 COPD patients aged 55 and older who were exposed to gabapentinoids between 1994 and 2015. These patients were matched with an equal number of COPD patients with epilepsy, neuropathic pain, or other chronic pain, but who did not receive gabapentinoids. The primary outcome measured was a severe COPD exacerbation requiring hospital admission or resulting in death. The study also found that gabapentinoid use was associated with an increased risk of moderate or severe exacerbations and respiratory failure in patients with neuropathic or other chronic pain. However, precision regarding the association in patients with epilepsy was limited.
It is important to note that the study had some limitations. The data used did not include information on race/ethnicity and smoking status, and there could have been potential misclassification of COPD if patients were prescribed long-acting beta-agonists/inhaled corticosteroids for asthma. Additionally, the study may have included a larger proportion of patients aged 65 and older due to the insurance coverage of prescription medication in Quebec for this age group.
This new study provides valuable insights into the association between gabapentinoid use and an increased risk of severe exacerbations in patients with COPD. The findings highlight the importance of considering the potential respiratory adverse effects of gabapentinoids when prescribing them to COPD patients. It is crucial for healthcare professionals to weigh the benefits against the risks and to ensure that guidelines for managing COPD and neuropathic pain reflect the latest evidence. Future studies are needed to further investigate these findings and to identify strategies for optimizing the management of COPD in patients with comorbidities requiring pharmacotherapy.