Chronic pain causes substantial suffering and disability worldwide. Several studies have shown that two-fifths of the UK population live with pain that has lasted for three months or longer. The National Institute for Health and Care Excellence (NICE) recommends that clinicians consider several other medicines classes before considering opioids for patients with chronic non-cancer pain. Recent research has highlighted the increase in gabapentinoid (gabapentin and pregabalin) use in pain management.
Gabapentinoids are anticonvulsant drugs that are used for preventing seizures, managing nerve pain and anxiety (pregabalin only). However, In the UK, gabapentin and pregabalin prescribing has increased by 350% and 150% between 2013 and 2017, respectively. Safety warnings were highlighted in 2016, following an increase in misuse and deaths associated with their use. As a result, the UK government recommended the classification of gabapentinoid as controlled drugs from April 2019.
We will evaluate the impact of pregabalin and gabapentin classification on prescribing trends and utilization for patients with chronic pain between 2005 and 2020. We will investigate the association between gabapentin and pregabalin prescribing and overdose and death. The findings of our study will inform prescribers and public health decision-makers about changes in gabapentin and pregabalin prescribing for chronic pain, the association between gabapentin and pregabalin use and related deaths, and the risk of occurrence of an overdose.
In the UK, gabapentin was licensed as an adjunct antiepileptic therapy for partial seizures and treating focal seizures in 1993. In 2000, gabapentin gained its approval as an analgesic for managing neuropathic pain and postherpetic neuralgia. Pregabalin was licensed in 2004 for treating neuropathy, postherpetic neuralgia, as an add-on drug to treat resistant partial epilepsy and generalised anxiety disorder.
A dramatic increase in the number of gabapentinoid (gabapentin and pregabalin) prescriptions has been reported between 2013 and 2017. Despite their limited efficacy for unlicensed pain indications, gabapentinoids are widely used off-label; up to 90% of prescriptions for pregabalin and 83% for gabapentin.
Both pregabalin and gabapentin have been reported as having the potential for misuse, which is increased with concomitant use of other substances, including opioids, alcohol, antidepressants, and psychostimulants. Gabapentinoid misuse could lead to medical consequences such as increase in emergency department visits and overdose deaths. Therefore, the UK government has recently classified these drugs as class C schedule 3 controlled substances in April 2019 after increasing off-label use, misuse and deaths.
We will conduct a drug utilisation study using CPRD data between January 1, 2005, and December 31, 2020. We will evaluate the impact of classification on prescribing trends; patterns of doses for pain conditions using Interrupted time series analysis. We will also investigate the association between the gabapentinoid prescribing and drug-related deaths and overdose. Our results will provide insight and impact of classification as to how gabapentinoids are prescribed for chronic pain in UK primary care. Moreover, it will highlight the potential risk of overdose and the related death associated with these medicines.
1. Prescribing trends, annual rates (incidence and prevalence) of gabapentinoid users for chronic pain (gabapentinoid users/ 10,000 registrants).
2. Gabapentinoid doses pattern for chronic non-cancer pain patients expressed by annual prescribed daily dose (PDD) per user per day and annual supply days.
3. The impact of gabapentinoid classification on drug utilisation (monthly prescribing trends and monthly gabapentinoid PDD per user per day).
4. The association between gabapentinoid prescribing (treatment) and the risk of overdose expressed as unadjusted and adjusted hazard ratios with corresponding 95% CIs.
5. The association between gabapentinoid prescribing (treatment) and related mortality expressed as unadjusted and adjusted hazard ratios with corresponding 95% CIs
Roger Knaggs - Chief Investigator - University of Nottingham
Joud Alfriah - Corresponding Applicant - University of Nottingham
John Williams - Collaborator - University of Nottingham
Sonia Gran - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation