There are approximately 260,000 people in England that regularly use heroin. Heroin use is associated with increased risk of death due to overdose and infection and has a significant impact upon the user’s quality of life. Heroin users have higher rates of unemployment and often resort to theft and other crimes to fund their habit. Methadone, like heroin, is a type of drug known as an opioid. Methadone maintenance therapy (MMT) aims to reduce heroin addiction by countering the cravings and symptoms associated with heroin withdrawal. However, like all opioids, methadone can have unpleasant side effects including opioid induced constipation (OIC) which can impair quality of life and possibly cause the patient to reduce methadone either partially or totally. This increases the risk of relapse. The purpose of this study is to select patients initiating methadone within the Clinical Practice Research Datalink and to estimate how many develop OIC and how many are unable to control OIC using standard laxative treatments. We then wish to see whether presence of OIC is associated with patients to discontinue MMT and whether this in turn relates to increased rates of relapse and mortality. We also wish to estimate how OIC affects patients use of general practice and hospital services and the excess cost of these services. This study will provide valuable information about the impact of OIC related to MMR and may highlight potential treatment options that may improve MMT effectiveness and reduce overall healthcare burden in the National Health Service.
Methadone maintenance therapy (MMT) aims to reduce the cravings and withdrawal symptoms associated with illicit diamorphine (heroin) use and has proven efficacy in reducing rates of addiction. However, methadone has side effects including opioid induced constipation (OIC) which may affect patient compliance with MMT regimens. This study aims to select patients initiating MMT in the Clinical Practice Research Datalink Aurum database linked to the Hospital Episode Statistics (inpatient, outpatient and accident and emergency) and ONS (mortality and index of multiple deprivation) datasets. We then wish to estimate how many of these patients develop OIC based on diagnoses and/or prescriptions for laxatives, and to estimate how many patients are adequately controlled (stable OIC) versus uncontrolled (unstable OIC) on their current treatment regimens. The impact that OIC status has on primary and secondary care utilisation and costs, compliance with MMT regimens and mortality outcomes will be assessed. MMT episodes for patients of acceptable research quality and eligible for linkage to all datasets will be selected from 1st January 2010 to 31st December 2019. Demographic characteristics and baseline comorbidity at index date will be summarised. Time from index date to end of MMT therapy (discontinued or censored) and proportion of patients classified with OIC and stable/unstable will be reported. Inpatient, outpatient and accident and emergency department contacts will be aggregated and compared between the OIC defined sub-groups. Rates will be compared between sub-groups using Poisson Regression and costs will be compared using the Gamma distribution. For discontinuation and mortality, crude rates and Kaplan-Meier curves will be presented. OIC will be modelled as a time-dependent variable in a Cox Proportional Hazards model for both discontinuation and mortality outcomes adjusting for other co-variates including the index of multiple deprivation.
Prevalence of opioid induced constipation, primary care contacts; primary care costs; secondary care contacts, secondary care costs; methadone discontinuation; diamorphine relapse; mortality.
Christopher Morgan - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Christopher Morgan - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Andrew Cooper - Collaborator - Shionogi BV
Bethan Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
peter conway - Collaborator - Shionogi BV
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation