The effect of a methadone reformulation on opioid agonist treatment outcomes: A population-based study in British...

The province of British Columbia, Canada, changed the existing oral anhydrous methadone solution to a 10-times more concentrated pre-mixed solution, Methadose®, on February 1, 2014. We aimed to assess the immediate effects of the methadone reformulation on missed doses, days off methadone, changes in medication dosing and dispensations of opioids for pain, and hospitalizations and mortality among all people receiving treatment at or near the time of the change.

We conducted a population-based retrospective cohort study including all individuals receiving at least one methadone dispensation in the 12 months prior to the study period. We executed a difference-in-differences analysis by estimating a multivariate regression model to compare outcomes in the three months before and after the reformulation (November 1, 2013 to April 30, 2014) versus a time-lagged control cohort with similar characteristics observed during an equivalent nonoverlapping interval. We used daily individual-level linked health administrative data capturing missed doses, days off methadone, changes in methadone dosing, concurrent dispensations of opioids for pain, hospitalizations, and mortality. We stratified the cohorts into three subgroups: (i) those receiving OAT for ≥12 months; (ii) those receiving OAT for <12 months; and (iii) those not receiving OAT at the start of the study period. We conducted sensitivity analyses and placebo tests to assess the robustness of our results.

Among the 16,339 individuals receiving methadone during the study period, the reformulation was associated with more instances of methadone dose increases (34.5% [95% Confidence Interval (CI): 27.4%, 41.5%]). For those retained in treatment ≥12 months prior to the study period (n = 7449), the reformulation was associated with more instances of methadone dose increases (50.2% [39.5%, 60.8%]) and dispensations of opioids for pain (62.2% [40.8%, 83.5%]), as well as an increase in missed doses (41.9% [29.1%, 54.7%]) and days off methadone (62.6% [39.7%, 85.4%]). We found no statistically significant change in risk of hospitalization or mortality. Sensitivity analyses supported our results.

Our results reinforce the need expressed by people receiving methadone for greater client involvement in the planning and implementation of regulatory changes that may impact client care, especially those patients with a relatively long treatment history.