Student thesis: Phd


Background: The varying association between different periods of exposure to Opioid Agonist Treatment (OAT) and fatal drug-poisoning risk has been widely studied worldwide. However, little is known about the risk of non-fatal overdose during OAT initiation and cessation and during co-prescription of OAT with other medications, especially between methadone and buprenorphine recipients. Patients with substance use disorders have complex healthcare needs that often remain unmet. Research on primary and secondary healthcare utilisation can be informative, thereby enhancing our understanding of the frequency at which patients have primary care consultations, inpatient stays, outpatient visits, and emergency department attendances. To date, research on non-fatal overdose is scarce, especially for methadone and buprenorphine recipients and no relevant studies have examined the potential association between increased healthcare utilisation and elevated costs in England. Methods: Patient-level data from general practices in England in the Clinical Practice Research Datalink (CPRD) were interlinked to secondary care records, ecological deprivation measures and mortality records. The initial study cohort included 20,898 patients, aged 18-64 years who were prescribed OAT. Multiple statistical methods have been applied, including inverse probability of treatment weighting, and Poisson, negative binomial, and Cox regression. Results: Patients who were prescribed OAT were at an elevated risk of non-fatal overdose during the first four weeks of treatment initiation and four weeks following treatment cessation. In addition, buprenorphine was associated with lower non-fatal overdose risk compared to methadone, especially during the first four weeks of treatment. An elevated non-fatal overdose risk has also been observed among patients who had been co-prescribed OAT with benzodiazepines, gabapentinoids, z-drugs, or antipsychotics. More frequent healthcare utilisation and consequent higher average costs have been observed for methadone recipients across primary and secondary care. Conclusion: It is known that overdose is a risk factor for subsequent non-fatal or fatal overdose. The findings from this doctoral research programme highlighted the increased non-fatal overdose risk during treatment initiation and cessation in relation to methadone versus buprenorphine treatment and during co-prescription of OAT with other medications. The observed differences in healthcare utilisation and related costs of care are potentially related to differences between methadone and buprenorphine recipients, leading to the following important recommendations: (1) the need for collaborative delivery of healthcare for patients with complex opioid use disorder who have physical and mental health comorbidities; (2) increased OAT engagement of patients following a non-fatal overdose; and (3) regular revision of patients treatment plans. Prevention of overdose among patients with co-occurring opioid use disorder and physical or mental illness needs closer attention and both primary and secondary healthcare services can play a pivotal role in identifying patients at high risk of overdose and then referring them to specialist services.
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorTimothy Millar (Supervisor), Roger Webb (Supervisor), Darren Ashcroft (Supervisor) & Matthew Carr (Supervisor)


  • Opioid use disorder
  • Clinical Practice Research Datalink
  • Electronic Health Records
  • Substance misuse
  • Buprenorphine
  • Methadone
  • Overdose

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