Analysing the impact of gabapentinoid reclassification on prescribing rates in the UK

Background & Aims
Neuropathic pain can arise from a disease or lesion effecting the somatosensory system[1]. To help manage such pain, gabapentinoids are recommended as first-line medications[2]. In April 2019, following an increase in deaths and drug misuse[3], gabapentinoids such as gabapentin and pregabalin were reclassified as Class C drugs in the UK[4]. The use of gabapentinoids was found to lead to an increased risk of unintentional overdoses, suicidal behaviour and road accidents, with pregabalin being associated with higher hazards than gabapentin[5]. This study aims to identify changes in prescription trends in the UK based on number of defined daily doses (DDDs) for gabapentin and pregabalin since the reclassification in April 2019.

Methods
Prescribing data was obtained through open-source NHS data for Scotland[6], England[7], Wales[8], and Northern Ireland[9]. Interrupted time series analysis (ITSA) was performed using linear regression modelling, looking at number of DDDs per 1000 population per month for years 2018-2022 for England, Wales, and Northern Ireland, with the intervention (i.e. gabapentinoid reclassification) occurring in April 2019. Scottish data from years 2016-2022 was used, which allowed for a more robust analysis than that for England, Wales and Northern Ireland. If DDDs were not present in original data, they were obtained using strength of prescription and item quantities, divided by the World Health Organisation’s (WHOs) DDD for gabapentin (1800mg) and pregabalin (300mg)[10]. Relative change was calculated by comparing the real data post-reclassification to counterfactual values had the intervention hypothetically not occurred.

Results
In England, Wales and Scotland, we observed a significant positive prescribing trend in pregabalin DDDs per 1,000 population (2.40, 3.10 and 2.80 DDDs per 1,000 population per month, respectively, p<0.05), no significant changes in level, and significant negative changes in trend following reclassification (-1.52, -2.37 and -0.62 DDDs per 1,000 population per month, respectively, p<0.05). No significant changes were found in Northern Ireland. A negative relative change was observed for all four countries, between -24.09% and -0.59% for both gabapentinoids. Although a negative relative change was seen, the number of DDDs per 1,000 population post-reclassification continued to show a significant positive trend (p<0.05), except in Northern Ireland where a significant negative trend was observed (p<0.05). No significant changes in level or trend post-reclassification for gabapentin were seen in any country, except in Scotland where a significant negative change in level was seen (p<0.05).

Conclusions
Based on the results obtained from the ITSA analysis, we found that although a negative relative change was seen for Scotland, England and Wales, the only significant changes in prescription trends were found for pregabalin, whereas no significant changes could be seen for prescription trends for gabapentin post-reclassification in April 2019. The reclassification of gabapentinoids in April 2019 has not resulted in any significant changes in prescribing rates. Although Northern Ireland had a significant post-reclassification trend in prescribing for both gabapentinoids (positive for gabapentin and negative for pregabalin), the change in prescribing trend from pre- to post-reclassification was not significant, and neither was the change in level. The trends are consistent across Scotland, England and Wales, but with a contrast in Northern Ireland. Further work will examine the changes in rates of gabapentinoid-related deaths for all countries within the UK, based on monthly numbers.