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Gabapentinoids for Pain: A Review of Published Comparative Effectiveness Trials and Data Submitted to the FDA for Approval

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Abstract

Use of the gabapentinoids for pain continues to increase. In 2018, the US Food and Drug Administration (FDA) strengthened the warnings for both gabapentin and pregabalin to emphasize the central nervous system side effects and the risk of respiratory depression, especially when combined with other centrally acting drugs. We reviewed the published comparative effectiveness literature for gabapentinoids for pain as well as all trials (published and unpublished) used by the FDA for the approval of the five pain indications for these agents (one for gabapentin, four for pregabalin). Among the findings of interest are the fact that the FDA rejected the application for gabapentin for diabetic peripheral neuropathy based on the risk versus benefit profile of that drug in the clinical trials that were submitted by the manufacturer. Additionally, both the comparative effectiveness trials as well as the studies used by the FDA tend to be short in duration and show only modest pain benefits for the gabapentinoids. The placebo response in these trials was frequently one-third to one-half as great as the pain benefit demonstrated by the gabapentinoid. Based on the available clinical trial evidence, we feel prescribers should be cautious when using gabapentinoids for pain, particularly when using these agents for a prolonged period or when combined with other, centrally acting agents.

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Acknowledgements

The authors would like the thank Erick Turner, MD at the VA Portland who provided valuable insight into the processes of obtaining and reviewing FDA drug reviews.

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Authors and Affiliations

  1. Oregon State University College of Pharmacy, 2730 SW Moody Ave., CL5CP, Portland, OR, USA

    C. D. Williams, Z. Al-Jammali & M. C. Herink

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  1. C. D. Williams
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  2. Z. Al-Jammali
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  3. M. C. Herink
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Correspondence to C. D. Williams.

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The data that support the findings of this study are available on request from the corresponding author.

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All authors conducted an independent review of the FDA review packets and of Pubmed for relevant clinical trials. CDW: conceptualization, supervision, writing, review, and editing. ZAJ and MCH: writing, review, and editing.

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Williams, C.D., Al-Jammali, Z. & Herink, M. Gabapentinoids for Pain: A Review of Published Comparative Effectiveness Trials and Data Submitted to the FDA for Approval. Drugs 83, 37–53 (2023). https://doi.org/10.1007/s40265-022-01810-3

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