Gabapentin and pregabalin (gabapentinoids) are medicines used to treat epilepsy and nerve pain. Use of gabapentin and pregabalin has increased considerably. In the UK, around 12 million gabapentinoid prescriptions were issued in 2016 compared to 1.5 million in 2006. Gabapentinoids are commonly prescribed in the UK yet little is known about the patients taking them or why they are prescribed, although pain is thought to be the commonest reason. Research shows that gabapentinoids benefit only one-fifth of people with nerve pain and there is little research evidence that demonstrates their effectiveness for other pain conditions. Studies show that they do not help people with chronic back pain. Around six in every ten people experience side-effects with gabapentinoids, including dizziness, feeling sleepy and unsteadiness. There are also increasing reports that gabapentinoids are being misused or abused. Overdoses involving gabapentinoids are increasing and, in the UK, deaths involving gabapentinoids rose from 12 in 2012 to 170 in 2016. Following concerns about rising use and misuse of gabapentin and pregabalin, the UK government has reclassified gabapentinoids as controlled substances. However, little is known about the risks to patients, without a history of drug abuse, who are legitimately prescribed gabapentinoids. Using routinely collected health information from the Clinical Practice Research Datalink (CPRD), we propose to assess the prevalence and pattern of prescribing gabapentinoids and whether those prescribed these drugs are more likely to develop serious adverse events.
Background
Gabapentin and pregabalin (gabapentinoids) are medications licensed for epilepsy and neuropathic pain. Pregabalin is also licenced for anxiety disorders. Marked year-on-year increases in gabapentinoid prescribing suggest widespread off-label prescribing for other pain conditions, despite limited evidence of effectiveness. Increasing reports of misuse and gabapentinoid-related deaths have resulted in the reclassification of gabapentinoids as controlled drugs. However, most reported adverse events occur in high-risk populations and the risk of gabapentinoid-related adverse events in the wider patient population is unknown.
Aims and Objectives
We will investigate trends in UK gabapentinoid prescribing, including likely indications and determine the risks of and risk factors for major trauma/falls, drug misuse and overdose in primary care patients.
Methods
Work Package 1
We will identify patients aged ?18 years in CPRD practices and issued ?1 gabapentinoid prescription (1997-2019). Repeated cross-sectional analyses will calculate point and period prevalence of gabapentinoid prescribing each year, stratified by age and gender. We will also investigate whether the change in licensing in April 2019 has resulted in a change in incident and prevalent prescribing.
In patients with incident gabapentinoid prescriptions, we will extract information on licensed indications (epilepsy, neuropathic pain, anxiety), chronic pain conditions representing unlicensed indications (expert consensus), and concurrent prescribing (opioids, benzodiazepines, hypnotics, antidepressants). We will identify the proportions with licensed/non-licensed indications and describe therapy dose/duration, prior prescribing pathway and concurrent prescribing.
Work Package2
We will compare patients with incident gabapentinoid prescriptions to patients not prescribed gabapentinoids regarding incidence of major trauma/falls, drug misuse, and overdose.
We will use self-controlled case-series methodology to better account for between-person confounding when investigating adverse events in gabapentinoid users.
Work Package 3
We will assess potential risk factors for adverse events in patients prescribed gabapentinoids, (e.g. socio-demographics, lifestyle factors, comorbidities, co-prescriptions), using multivariable Cox regression to examine associations between potential risk factors and adverse events.
Gabapentin and pregabalin prescriptions (Workpackage 1); Serious adverse events (major trauma/falls, drug misuse/addiction, overdose) in patients prescribed gabapentinoids (Workpackage 2 and 3).
Julie Ashworth - Chief Investigator - Keele University
Ram Bajpai - Corresponding Applicant - Keele University
Christian Mallen - Collaborator - Keele University
Deborah Hickson - Collaborator - Not from an Organisation
Rebecca Whittle - Collaborator - Keele University
Sara Muller - Collaborator - Keele University
Sarah Harrisson - Collaborator - Keele University
Toby Helliwell - Collaborator - Keele University
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation