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Misuse of Pregabalin and Gabapentin: A Second Systematic Review Update
Kirk E Evoy1, Daija Drain2, Justin Pedigo2
1College of Pharmacy, The University of Texas at Austin, San Antonio, TX, USA. evoy@uthscsa.edu.
Drugs
|June 3, 2026
Summary
Gabapentinoid misuse, including gabapentin and pregabalin, is a growing public health concern. New evidence confirms increased overdose risks, especially when combined with opioids or benzodiazepines.
Area of Science:
- Pharmacology and Toxicology
- Public Health
- Addiction Medicine
Background:
- Previous systematic reviews identified significant gabapentinoid misuse, dependence, and overdose cases.
- An update in 2021 confirmed 114 studies on gabapentinoid (gabapentin and pregabalin) misuse.
Purpose of the Study:
- To update existing systematic reviews on gabapentinoid misuse.
- To identify and analyze new insights into gabapentinoid misuse, dependence, and overdose.
Main Methods:
- Searched PubMed from September 2020 to January 2025 for studies on gabapentinoids and substance misuse.
- Included studies presenting novel data on misuse, dependence, or overdose; excluded non-English, review, and animal studies.
Main Results:
- 100 new studies (87 observational, 13 case reports) were analyzed.
- Gabapentinoid misuse often occurs with opioids or other substances, particularly in individuals with substance use and psychiatric disorders.
- Concomitant use with opioids or benzodiazepines significantly increases overdose risks.
- Emerging evidence highlights misuse in the Middle East, North Africa, among adolescents, and in chronic pain patients.
Conclusions:
- Newly published evidence confirms gabapentinoid misuse remains a significant issue.
- Increased overdose risk associated with gabapentinoids, especially when combined with opioids or benzodiazepines, is strongly supported by recent data.
- Gabapentinoid misuse is increasingly recognized in previously underrepresented populations and regions.
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