Comparative Effectiveness of Opioid Tapering or Abrupt Discontinuation vs No Dosage Change for Opioid Overdose or Suicide for Patients Receiving Stable Long-term Opioid Therapy

Key Points Question For patients receiving stable long-term opioid therapy compared with a stable opioid dosage, what is the association of opioid dosage tapering or abrupt discontinuation with opioid overdose or suicide? Findings In this comparative effectiveness study of 415 123 episodes of stable long-term opioid therapy among 199 836 individuals, opioid tapering was associated with a small absolute increase in opioid overdose or suicide compared with a stable opioid dosage. No significant difference in outcomes between abrupt discontinuation and stable opioid therapy was identified. Meaning These findings do not support opioid dosage tapering as a strategy to reduce harms for patients receiving stable long-term opioid therapy without evidence of misuse.


Calculating daily Morphine Milligram Equivalents (MME).
We used the CDC Opioid NDC and Oral MME Conversion File to identify opioid analgesics by National Drug Code (NDC) and their associated MME conversion factors. 1 We excluded liquid antitussive and intravenous formulations not used for outpatient treatment of pain, and buprenorphine given lack of an agreed upon conversion factor. Pharmacy claims contain the quantity dispensed and days supply for each prescription. We calculated the MME for each prescription by multiplying the quantity by the strength and MME conversion factor.
We attributed the MME equally over the days supply starting with the dispensing date. We summed the MME on days where more than one prescription overlapped. We calculated the mean MME for each calendar month by dividing the sum of the MME on each day divided by the number of days in each month.

Defining early refills.
We defined an early refill as a medication for the same opioid formulation and strength (e.g. 5 mg oxycodone tablets) filled more than 3 days prior to the run out date (dispensing date plus days supply) of the prior prescription.

Specification of regression models to derive weights.
Treatment weights were calculated to adjust for informative censoring of clones during the treatment assignment period. We developed separate logistic regression models for each month and treatment strategy, controlling for potential confounders identified in the Methods, and used them to calculate the predicted probability of complying with the assigned strategy in each month of the treatment assignment period. The treatment weights were calculated as the inverse of the predicted probability of complying with the assigned strategy.
Censoring weights were derived to adjust for selection bias from loss to follow-up. We used a pooled logistic regression model to estimate the probability of not being disenrolled from the health plan adjusting for potential confounders plus a term for month. Censoring weights were defined as the inverse of the probability of being uncensored in each month.
b In this sensitivity analysis, tapering was defined as a single month (rather than two consecutive months) of a dose decrease of 15% more than baseline during the treatment assignment period, and abrupt discontinuation was defined as a month meeting tapering criteria with a mean MMME of 0 mg per day.

eFigure. Illustrative Examples of Treatment Assignment, Cloning Procedures, and Censoring
Legend: 100% Mean dose as % of baseline month >85% 1-85% 0% A value of 1 indicates clone remains in the analysis, and 0 indicates censoring.
Censoring in per protocol approach when dose no longer consistent with treatment strategy.