ALFRIAH, JOUD
(2024)
Gabapentinoid use, risks, and the impact of reclassification for chronic pain patients in the United Kingdom.
PhD thesis, University of Nottingham.
Abstract
Background: Chronic pain is a significant health concern in the UK, leading to increased use of pregabalin and gabapentin beyond their original indications for epilepsy, anxiety, and neuropathic pain. This expanded, often unlicensed use has raised concerns due to limited efficacy evidence and misuse risks, especially with opioids. Consequently, gabapentinoids were reclassified as Schedule III controlled drugs in the UK in 2019. This study utilised CPRD data to examine gabapentinoid prescribing patterns from January 2005 to December 2020 and assessed the impact of reclassification on prescribing trends, focusing on chronic pain patients. Moreover, it explored the association between gabapentinoid use and harms from August 2012 to July 2020.
Methods: This study employed pharmacoepidemiological approaches, comprising a repeated cross-sectional analysis to examine prescribing patterns in chronic pain patients, an interrupted time series to assess the impact of gabapentinoid reclassification, and a cohort study to investigate the association with overdose and mortality.
Results: There was a significant increase in gabapentinoid prescriptions in a cohort of 415,179 people with chronic pain. The prevalence of gabapentin and pregabalin users escalated from 38.8 to 125, and from 12.8 to 108.9 per 10,000 registrants, respectively. Incidence rates of new users also surged, with gabapentin increasing from 13.8 to 49.7, and pregabalin from 8 to 38.5 per 10,000 registrants. Over 60% of prescriptions were for unlicensed indications, primarily chronic back pain, while nearly 20% were for licensed uses. The reclassification of gabapentinoids resulted in a 13% and 18% decrease in the monthly prevalence of pregabalin and gabapentin users per 10,000 registrants, respectively. Time-varying analysis showed a significant association between current gabapentinoid use and harms, with hazard ratios (HRs) of 1.61 and 1.57 for overdose, and 1.19 and 1.12 for all-cause mortality, for gabapentin and pregabalin, respectively.
Conclusion: There was a significant rise in gabapentinoid prescriptions for chronic pain from 2005 to 2020, notably for unlicensed purposes. Reclassification led to a reduction in both gabapentinoid users and doses. Significant associations between gabapentinoid use and increased overdose and mortality risks were also identified. These findings inform policy and prescribing guidelines for safer gabapentinoid use in chronic pain patients, highlighting the need for targeted misuse prevention and intervention programmes
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