Prescribed alternative stimulants among people who use unregulated stimulants: Examining the association between maximum dose reached and medication discontinuation in the first 3 years of implementation in British Columbia, Canada

BACKGROUND AND AIMS: In 2020, British Columbia (BC), Canada, introduced 'Prescribed Alternatives' (PA) as an approach to offering regulated substances to people accessing the unregulated supply. This study aimed to estimate and compare prescribing characteristics of dextroamphetamine and methylphenidate stimulant PAs in BC, to estimate medication discontinuation probabilities for each PA type by episode order, and to estimate the hazard ratio for medication discontinuation comparing episodes that reached a maximum daily stimulant PA dose of ≥60 mg/day with episodes that did not. DESIGN: Population-based retrospective cohort study using linked provincial administrative health data. The analysis included people who were identified to have received a stimulant PA prescription between 27 March 2020 (the day after guidance for prescribing PAs was released in BC) and 31 July 2023. The study was reported in accordance with the STROBE guideline. SETTING: BC, Canada (27 March 2020-31 July 2023). PARTICIPANTS: People who received stimulant PA prescriptions during the study period in BC. These were people who use unregulated stimulants and who, in the judgement of their prescriber, might benefit from prescribed psychostimulants from either a treatment or harm reduction perspective. A total of 1683 people (35.6% female) contributed 4842 stimulant PA medication episodes (dextroamphetamine or methylphenidate) to the study. MEASUREMENTS: The primary outcome was time to medication discontinuation within each stimulant PA episode. The primary exposure was reaching a daily dose of ≥60 mg. Prentice, Williams and Peterson's Gap Time survival models were used to estimate adjusted hazard ratios for discontinuation by dose, adjusting for demographic (sex, age, health authority) and clinical covariates [stimulant prescription history, opioid agonist treatment (OAT) prescription history and concurrent OAT prescription during episodes]. FINDINGS: Most episodes remained at the initial dispensed dose, with only 25.8% of dextroamphetamine and 38.4% of methylphenidate episodes reaching ≥60 mg/day. Episodes that did not reach this threshold had a higher hazard of discontinuation compared with those that did [hazard ratio (HR) = 1.21; 95% confidence interval (CI) = 1.11-1.32 for dextroamphetamine; HR = 1.12; 95% CI = 1.00-1.25 for methylphenidate]. While robust dosing was associated with improved retention, discontinuation remained high overall, and stimulant PA uptake was low relative to estimated eligibility. CONCLUSIONS: Doses of stimulant prescribed alternatives (dextroamphetamine and methylphenidate) that reach 60 mg or more per day appear to be associated with longer treatment episodes than lower doses. Discontinuation is high across both medications. Concurrent opioid agonist treatment appears to be associated with a lower hazard of discontinuation. Dosing alone is unlikely to sustain long-term engagement for all patients.