Gabapentin and pregabalin are a group of medicines known as gabapentinoids, commonly used for treating epilepsy and neuropathic pain (a complex chronic pain condition caused by damage or disease that results in problems with signals from the nerves). Over the past decade, the number of prescriptions of gabapentinoids has increased dramatically in the United Kingdom (UK), especially in patients with various chronic pain conditions, such as lower back pain and arthritis. Meanwhile, the number of deaths involving gabapentinoids has increased too. Due to the increasing concerns in misuse and overuse, gabapentinoids were classified as controlled drugs from April 2019, and thereafter all prescriptions need to be hand-signed by doctors. Studies in other countries had found a higher risk of opioid-related deaths when patients combined gabapentinoids with opioids. However, the risks of other serious events potentially associated with gabapentinoids, such as bone fracture, suicide and drug-related death, are still unknown in the UK. With the increasing number of gabapentinoids prescribed every year it is important to study the safety issues related to gabapentinoids and factors that potentially cause harm to patients. This study will investigate the risks of serious adverse events associated with the prescribing of gabapentinoids in patients with chronic pain conditions and identify factors that may increase the risk. The results will help general practitioners to recognise patients at higher risk of developing the adverse outcomes and avoid potential harms when prescribing these medicines.
Gabapentin and pregabalin (known as “gabapentinoids”) are medicines indicated for focal seizure and neuropathic pain. In the past decade, there has been a marked increase of gabapentinoids prescribed in the United Kingdom (UK) primary care setting predominantly for patients with chronic non-cancer pain (CNCP). There is also an increase in drug-related deaths involving gabapentinoids. Due to the concern in misuse, abuse and illegal diversion, gabapentinoids were classified as controlled C drugs in the UK from 1st April 2019. Previous literature found gabapentinoids increased the risk of death in opioid users, probably by enhancing the respiratory inhibition led by opioids. Furthermore, case reports found a risk of suicide in gabapentinoid users. However, there is currently no study assessing these safety issues using healthcare databases in the UK. This study aims to evaluate the risk of serious adverse events in gabapentinoid users with CNCP by different epidemiology study designs using a UK primary care database. Firstly, a cross-sectional study will describe the trend and pattern of gabapentinoid utilisation in patients with CNCP by using data from CPRD. Secondly, a matched-cohort study will assess the prevalence of bone fracture, drug-related death and suicide between gabapentinoids users and their matched control by using CPRD linking to HES and ONS death registry. Thirdly, a nested case-control study will investigate the effect of combining gabapentinoids with other analgesics on drug-related death. Finally, two self-controlled studies will assess the risk of bone fracture and suicide (both suicidal behaviour and completed suicide) in different periods of exposure in gabapentinoid users with CNCP. The results of the study will provide important medication safety information to inform clinical decision-making. It will help general practitioners identify risk factors that may increase the risk of adverse events during the period that needs strict monitoring and reduce the risk of gabapentinoids.
Serious adverse events related to gabapentinoids: hospital admission due to bone fracture of major arthrosis (exclude stress and pathological bone fracture); drug-related death; hospital admission or death due to suicide.
Li-Chia Chen - Chief Investigator - University of Manchester
Li-Chia Chen - Corresponding Applicant - University of Manchester
Darren Ashcroft - Collaborator - University of Manchester
Douglas Steinke - Collaborator - University of Manchester
Teng-Chou Chen - Collaborator - University of Manchester
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation