The trends and rates of gabapentin and pregabalin

Abstract

Background: Gabapentinoids were initially introduced for the treatment of epilepsy, then became more widely used in neurology, psychiatry and primary healthcare for the treatment of neuropathic pain. However, gabapentinoids have frequent and debilitating side effects, including viral infection, visual disturbance, nystagmus, fever and fatigue, andrecent evidence suggests that they are increasingly misused. What is more, recent studies have found the number of drug-related deaths in which gabapentinoids are implicated is rising. Detailed and published evidence on the prescribing rates and trends of gabapentin and pregabalin is limited. Identifying the prescribing rates and trends of gabapentinoids will help us to quantify the scale of the issue and allow us to examine whether there are associations with demographic factors and subsequent health outcomes.

Objective: This research work consists of two projects. (Part 1) The systematic review, aims to summarise the current published evidence on the trends and rates of gabapentin and pregabalin prescribing among the general population. (Part 2) The data-linkage analysis, aims to summarise the gabapentin and pregabalin prescribing patterns in Tayside over 11 years (2006 to 2016) and Fife over seven years (2010 to 2016). As well as the association of prescribing patterns with sociodemographic factors, the use of related health services was also examined by using routinely available linked data for 2015 and 2016.
Methods: (Part 1) Current published evidence was collected by the following steps: constructing a search strategy for searching selected key databases; selecting papers based on the selection criteria, data abstraction and quality assessment; preparing a table summary for the included papers; and summarizing the included citations.(Part 2) A large dataset including 1,091,199 prescriptions and data-linkage from data prepared by Health Informatics Centre (HIC) services was analysed. The prescribing patterns of gabapentinoids in Tayside over 11 years (2006 to 2016) and Fife for seven years (2010 to 2016) were summarised and compared with Scottish national data using Excel and SPSS. The 36,800 patients who were prescribed at least one gabapentin orpregabalin in Tayside and Fife during 2015 and 2016 were linked with the demographic file, SMR06 cancer register file, SMR01 hospital admission file, GRO death data, accident and emergency data and SMR00 outpatient file, using routine data obtained from HIC at the University of Dundee. The association of prescribing patterns with socio-demographic factors was examined using both logistic regression modelling and Poisson modelling; while their association with using the health services was investigated by a correlation graph. The age standardised mortality and the underlying cause of death were also calculated and summarised.
Results: (Part 1) 529 non-duplications were retrieved and 17 citations were included following the process of paper selection. The trends of gabapentin and pregabalin prescribing varied from country to country: rise, decrease and fluctuation. The rates of gabapentin and pregabalin prescribing varied in different countries within the same year. Among the 17 papers, there were five papers of high quality, nine papers of medium quality and three papers of low quality.(Part 2) The number of gabapentin prescriptions in Scotland rose 4-fold from 164,630 in 2006 to 694,293 in 2016. In Tayside these figures were 16,481 in 2006 to 57,472 in 2016 (x3.5). In Fife, there were 20,465 prescriptions issued in 2010, rising to 65,241 in 2016 (x3.2). Similar rises in the number of pregabalin prescriptions were charted in Scotland (x16.1), Tayside (x21.4) and Fife (x2.4). Health board, age and The Scottish Index of Multiple Deprivation (SIMD) were significantly related to rates of gabapentin and pregabalin prescribing. The age standardised death rate among the population prescribed gabapentinoids was significantly higher than that reported among the Scottish general population (p<0.001).
Conclusion: (Part 1) The systematic review found that trends of gabapentin and pregabalin prescribing varied in different countries. Because of the limitations of these papers, a further and more comprehensive epidemiological study is needed to identify the trends of gabapentin and pregabalin prescribing in a general population.(Part 2) The overall trends were for gabapentin and pregabalin prescribing rates to rise in Tayside and Scotland from 2006 to 2016 and in Fife from 2010 to 2016. Age, SIMD, health board and some levels of rurality were associated with gabapentin and pregabalin prescribing rates. Associated mortality was higher than that in the Scottish general population which implied an association between gabapentinoids use and death.rate. Further research to investigate the reasons for these findings is needed.

Date of Award	2019
Original language	English
Supervisor	Blair Smith (Supervisor) & Jennifer Watson (Supervisor)