Gabapentinoids are a class of medications originally developed to treat seizures. They are now also given to patients for different conditions, including nerve pain, mental illnesses and sleeping problems. Yet, we do not know much about their safety of use. Many people taking them are also on other drugs that could affect their safety profile. There is a knowledge gap for us to find out more about the safety related to the use of gabapentinoids.
The proposed study will study how taking gabapentinoids affects people's mental and physical health. We will compare the number of cases of mental and physical outcomes when people take gabapentinoids with the time when they don't. We will look at how the safety profile differs between the two major gabapentinoids, gabapentin and pregabalin. We will also look at whether other medical conditions such as mental illnesses, diabetes or heart diseases will affect the risk of the outcomes.
We will follow a large group of people who have taken gabapentinoids between 2000 and 2022. The study will investigate the cases of mental and physical outcomes with data from the CPRD. We hope that this study will help understand more about the safety profile related to the use of gabapentinoids. Given the increasing consumption of gabapentinoids in the UK and rest of the world, this study will have important policy, clinical, and public health implications. Doctors and patients will also be able to make better decisions about this class of medication.
Gabapentinoids, such as gabapentin and pregabalin, exert their clinical effects by inhibiting neuronal voltage-gated calcium channel currents. This occurs through impairment of the trafficking function of the α2δ subunits, which leads to a reduction in neurotransmitter release between synapses in the brain. Voltage-gated calcium channels are involved in various physiological functions throughout the body, including synaptic transmission in the central nervous system, smooth muscle contraction in the cardiovascular system, and hormone secretion in endocrine cells. With their pharmacological actions, the consumption of gabapentinoids may have effects beyond the central nervous system, impacting multiple body systems.
Our study will utilize a population-based self-controlled case series design, including individuals aged 18 or above who have received at least one prescription for gabapentinoids in the CPRD database between 1st January, 2000 and 31st December, 2022. The primary objective of our study is to compare the risk of psychiatric and somatic outcomes among patients who have been treated with gabapentinoids during periods of exposure to the medication versus unexposed periods. To compare the risks between gabapentin and pregabalin, a cohort study with propensity score matching will also be conducted.
Our analysis will involve estimating the incidence rate ratios (IRRs) using conditional Poisson regression. In addition, we will calculate adjusted IRRs along with their corresponding 95% confidence intervals to account for potential confounding factors. We will assess the overall exposure as well as examine predetermined exposure risk periods separately.
In our subgroup analysis, we will focus on patients with mental illnesses, type 2 diabetes, or cardiovascular diseases. We will also investigate whether the incidence rates ratios of the outcomes of interest differ when patients were prescribed with specific neuropsychiatric medications concomitantly.
Primary outcomes: Suicidal behaviour; Unintentional overdoses; Head/body injuries; Road traffic accidents; Hyperglycaemic event; Hypoglycaemic event; major cardiovascular events (acute coronary syndrome, stroke and myocardial infarction); Arrhythmias; Hypertension; Pulmonary Circulation Disorder
Secondary outcomes: Delirium; Respiratory failure; Asthma; Respiratory Tract Infection
Exploratory outcomes: Bleeding; Hypothyroidism; Fluid and electrolyte disorders; Peptic ulcer; Acute kidney injury; Episode of Hospitalisation
(Appendix 7-27)
Kenneth Man - Chief Investigator - University College London ( UCL )
Siu Chung Andrew Yuen - Corresponding Applicant - UCL School Of Pharmacy
Joseph Hayes - Collaborator - University College London ( UCL )
Li Wei - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation