Upscheduling codeine in Australia

Codeine is a weak opioid that is used predominantly to treat mild to moderate pain. It is no more effective than other non-opioid analgesics for short-term pain relief, and non-medical use of over-the-counter (OTC) medications containing codeine is associated with severe harm. In light of this evidence, on December 20th, 2016, the Australian Therapeutic Goods Administration (TGA) announced that from the 1 st of February 2018, medications containing codeine would require a prescription (Schedule 4). This rescheduling decision was contentious, and public submissions to the TGA highlighted divergent varied perspectives and concerns about what this change would mean when implemented. This thesis presents an investigation of the anticipated and actual impacts of rescheduling OTC codeine medications in Australia for individuals who use them regularly, and advances the identification of codeine dependence through validation of a codeine dependence screening tool.
The research described in this thesis consisted of three studies. In the first study (Chapter 2), based on the public submissions submitted to the TGA, a brief questionnaire about the most common issues raised was completed by individuals who regularly used codeine (codeine consumers; n=354), pharmacists (n=220), and general practitioners (GPs; n=120). Most consumers and pharmacists opposed the rescheduling, whereas only one-third of GPs held this position. Consumers and pharmacists reported concern about whether the rescheduling would assist in minimising codeine-related harms and rates of dependence. Pharmacists were also concerned about the burden regular GP appointments would create in terms of finances for consumers and time for GPs. However, most GPs did not report these concerns. This study helped to identify critical targets for educational campaigns when codeine was rescheduled, particularly regarding effective alternatives to OTC codeine. Additionally, differing views between consumers, pharmacists, and GPs reinforced the importance of pharmacovigilance in monitoring and evaluating the effectiveness of codeine rescheduling when the change came into effect in 2018.
The second and primary study (Chapters 3 and 4) consisted of a longitudinal cohort study of individuals who reported regular OTC codeine use before (N=260), during and after the rescheduling, and measured multiple outcomes. A baseline questionnaire was completed by participants in November 2017, before codeine was rescheduled (1st of February 2018), and follow-up questionnaires administered one month (end February 2018), four months (June 2018) and 12 months (February 2019) after rescheduling came into effect. The study achieved a retention rate of 67% at 12 months post rescheduling. Outcome measures included estimates of daily average codeine use (mg) and overall daily average opioid use (calculated using an oral morphine equivalent daily dose, in mg), assessment of opioid use disorder (OUD) (calculated using a modified Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV), pain and pain self-efficacy scores, anxiety and depression scores, and visits to their general medical practitioners and emergency department. A protocol paper outlining the planned methodology and analysis was published before work commenced.
The findings of the second study did not support the concerns raised by GPs and regular consumers of codeine in the first study. The cohort study demonstrated that rescheduling codeine in Australia was associated with significant reductions in average daily codeine consumption (mg) (from 64.3mg at baseline to 27.6mg 15 months later) and reduced prevalence of OUD (from 51% to 33%) in a cohort of individuals who regularly used the medication, without apparent adverse impacts on pain or measures of anxiety and depression.
In the final study (Chapter 5), a screening tool for codeine dependence was developed for use in countries where codeine remains available in low-dose formulations in pharmacies (at the time of writing, these countries include places such as the United Kingdom (UK), Canada, Denmark, Ireland, and South Africa). The aim was to design a brief screening tool that could accurately identify individuals with problematic codeine use and was appropriate for routine use in a community pharmacy. A previously developed prototype was validated against an established measure of substance use and dependence using outcome data from the longitudinal cohort study. This screening tool may support screening and brief interventions in countries where codeine remains available in pharmacies without a prescription.
In conclusion, despite predictions that rescheduling codeine would worsen outcomes for regular consumers, this PhD research generated evidence that rescheduling contributed to reduced rates of codeine use and codeine-related OUD, without measurable impacts on pain or mental health. The work demonstrates that longitudinal cohort studies following a drug policy change are critical: they provide insight into its effect on target populations at an individual level and complement population-level data in monitoring outcomes of interest. Finally, the research produced a valuable contribution in the form of a brief and validated screening tool appropriate for use in community pharmacies in countries where codeine remains available without prescription.