Quantity fluctuations of illicitly used opioids and overdose risk

Reduced opioid tolerance is believed to be associated with overdose risk, although this relationship has primarily been examined in the context of gaps and frequency of opioid use. We sought to assess how changes in the quantity of opioids used, as opposed to periods of abstinence or overall frequency of use, relate to overdose risk.

Among repeated visits of participants of a behavioral intervention trial from 2014 to 2016, we used multivariable logistic regression models fit with generalized estimating equations to examine the relationship between the percentage of opioid use days on which individuals used more or less than the quantity they used on average (i.e., quantity volatility) and the occurrence of opioid overdose.

Our sample included 290 four-month reporting periods among 63 participants (67% male). Opioid overdose events were reported by 28 (44%) participants during 48 (17%) reporting periods. Our measure of quantity volatility had a median of 20% (IQR 0.0-50.0). In multivariable analysis, using a quantity different than the quantity used on average on more than 20% of all opioid use days in the reporting period was significantly associated with odds of any opioid overdose (Adjusted OR = 3.55, 95%CI = 1.55-8.13, p = 0.003), controlling for confounders.

Quantity volatility of illicitly used opioids was positively associated with overdose risk and may contribute to the complex system of overlapping factors that influence overdose risk. Future observational research among opioid users should collect detailed opioid use data, including quantity used over time, to clarify the patterns that most elevate overdose risk.