Gabapentinoids in Pain Management
Gabapentinoids were first developed and marketed in the 1990s as an anticonvulsant [1]. Not long after this introduction, they were approved for the treatment of chronic neuropathic pain conditions [1]. Now, they are widely recognized for their use in treating some types of post-operative pain [1]. The most commonly recognized drugs in the gabapentinoid class are gabapentin (Neurontin) and pregabalin (Lyrica) [1].
Due partly to the patent expiration of gabapentin and the search for non-opioid pharmacotherapeutics, gabapentinoids’ off-label prescription rates have tripled in the US over the last 15 years [2]. In 2015, about 4% of adults in the United States were treated with this class of medications [3]. In several other countries, off-label prescription rates have increased as well [1]. Prescribed to treat acute nociceptive/neuropathic pain, gabapentinoids have become a fixture in perioperative multimodal analgesia routines [1],[4].
Despite their wide-spread use, gabapentinoid functionality, indications, and abuse liability are still being investigated [2]. Biologically, these drugs target the calcium channel α-2-δ (CCα2δ), a crucial physiological locus for managing neuropathic pain [2]. Consequently, physicians have unanimously agreed that the prescription of this class of medication makes sense in alleviating patients’ neuropathic pain [2]. Although clinicians are aware of the connection between gabapentinoids and CCα2δ, practitioners may not fully understand the complex channel, resulting in over-prescription or utility in inapplicable settings [2].
The inappropriate usage of gabapentinoids has been documented across several studies. For instance, they have been used to treat carpal tunnel syndrome [5]. This application is not substantiated by enough evidence to justify its widespread use and may even endanger patients: one study found that prolonged use after surgery (80 to 91 days post-release) was common among patients prescribed gabapentinoids pre-surgery [5]. Other medical conditions for which gabapentinoid treatments have not been effective include acute zoster pain, back pain, central neuropathic pain, HIV neuropathy, phantom limb pain, and pain due to spinal cord injury or traumatic nerve injury [3].
Now, recent studies call into question the efficacy of gabapentinoids in treating neuropathic pain. A 2020 meta-analysis of 281 trials compared these medications with controls to gauge patients’ postoperative pain intensity [1]. The difference between the gabapentinoids and the controls was not clinically significant and, at the height of chronic and subacute pain levels, they did not affect pain intensity at all [1]. These results conflict with the regular use of gabapentinoids in perioperative settings [1].
Data suggesting gabapentinoid overuse are troubling when considering the wide range of mild to adverse side-effects that these drugs can produce. In the aforementioned meta-analysis, gabapentinoid prescription correlated with a higher risk of postoperative dizziness and visual disturbance [1]. Other possible side effects include confusion, ataxia, respiratory depression, and delirium [4]. There is also a risk of addiction to gabapentinoids, especially in patients with a history of opioid use [3]. The combination of opioids and gabapentinoids can augment the risk of hospitalization and death [3]. Prescribing gabapentinoids to older adults or people with several comorbidities should be followed by careful monitoring [3].
Given in the increased scrutiny of gabapentinoids for pain management, clinicians are advised to reconsider their routine use of this form of medication [3]. Increased selectivity when using gabapentinoids during surgery, as well as a recognition of the particular risk factors associated with individual patients, will promote improved use of gabapentinoids [3].
References
[1] M. Verret et al., “Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis,” Anesthesiology, vol. 133, no. 2, p. 265-79, August 2020. [Online]. Available: http://doi.org/10.1097/ALN.0000000000003428. [Accessed September 3, 2020].
[2] H. McAnally, U. Bonnet, and A. D. Kaye., “Gabapentinoid Benefit and Risk Stratification: Mechanisms over Myth,” Pain and Therapy, p. 1-12, July 2020. [Online]. Available: http://doi.org/10.1007/s40122-020-00189-x. [Accessed September 3, 2020].
[3] C. W. Goodman and A. S. Brett, “Gabapentinoids for Pain: Potential Unintended Consequences,” American Family Physician, vol. 100, no. 11, p. 672-675, December 2019. [Online]. Available: https://www.aafp.org/afp/2019/1201/p672.html. [Accessed September 3, 2020].
[4] A. H. Kumar and A. S. Habib., “The Role of Gabapentinoids in Acute and Chronic Pain After Surgery,” Current Opinion in Anaesthesiology, vol. 32, no. 5, p. 629-634, October 2019. [Online]. Available: http://doi.org/10.1097/ACO.0000000000000767. [Accessed September 3, 2020].
[5] J. I. Billig et al., “Inappropriate Preoperative Gabapentinoid Use Among Patients With Carpal Tunnel Syndrome,” Journal of Hand Surgery, vol. 45, no. 8, p. 677-689, August 2020. [Online]. Available: http://doi.org/10.1016/j.jhsa.2020.04.011. [Accessed September 3, 2020].