Awareness among prescribers, pharmacists, and persons managing pharmacy benefits that authorization of a second opioid prescription doubles the risk for opioid use 1 year later might deter overprescribing of opioids. Knowledge that the risks for chronic opioid use increase with each additional day supplied might help clinicians evaluate their initial opioid prescribing decisions and potentially reduce the risk for long-term opioid use. Discussions with patients about the long-term use of opioids to manage pain should occur early in the opioid prescribing process.

In a representative sample of opioid naïve, cancer-free adults who received a prescription for opioid pain relievers, the likelihood of chronic opioid use increased with each additional day of medication supplied starting with the third day, with the sharpest increases in chronic opioid use observed after the fifth and thirty-first day on therapy, a second prescription or refill, 700 morphine milligram equivalents cumulative dose, and an initial 10- or 30-day supply. The highest probability of continued opioid use at 1 and 3 years was observed among patients who started on a long-acting opioid followed by patients who started on tramadol.

Based on the CDC Guideline for Prescribing Opioids for Chronic Pain, literature supporting long-term opioid therapy for pain is limited; research suggests an increased risk for harms with long-term opioid use. Early opioid prescribing patterns for opioid-naïve patients have been found to be associated with the likelihood of long-term use.

Because long-term opioid use often begins with treatment of acute pain (1), in March 2016, the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2). However, data quantifying the transition from acute to chronic opioid use are lacking. Patient records from the IMS Lifelink+ database were analyzed to characterize the first episode of opioid use among commercially insured, opioid-naïve, cancer-free adults and quantify the increase in probability of long-term use of opioids with each additional day supplied, day of therapy, or incremental increase in cumulative dose. The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy; the second prescription; 700 morphine milligram equivalents cumulative dose; and first prescriptions with 10- and 30-day supplies. By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics, these findings might inform opioid prescribing practices.

A random 10% sample of patient records during 2006–2015 was drawn from the IMS Lifelink+ database, which includes commercial health plan information from a large number of managed care plans and is representative of the U.S. commercially insured population (3). The data are provided in a deidentified format and the institutional review board at the authors’ institution deemed the study was not human subject research. Records were selected of patients aged ≥18 years who had at least one opioid prescription during June 1, 2006–September 1, 2015, and ≥6 months of continuous enrollment without an opioid prescription before their first opioid prescription. Patients excluded were those who had any cancer (other than nonmelanoma skin cancer) or a substance abuse disorder diagnosis in the 6 months preceding their first opioid prescription, or whose first prescription was for any buprenorphine formulation indicated for treatment of substance abuse.

Patients were followed from the date of their first prescription until loss of enrollment, study end date, or discontinuation of opioids, which was defined as ≥180 days without opioid use. The duration of use and number of prescriptions and cumulative dose (expressed in morphine milligram equivalents*) for the first episode of opioid use (defined as continuous use of opioids with a gap of no greater than 30 days) were calculated. The number of days’ supply and average daily dose in morphine milligram equivalents for the first prescription were also calculated. The first opioid prescription was categorized into six mutually exclusive categories: long-acting; oxycodone short-acting; hydrocodone short-acting; other Schedule II short-acting; Schedule III–IV and nalbuphine; and tramadol.†

The Kaplan-Meier statistic was used to estimate median time to discontinuation of opioid use; probability of continued opioid use at 1 year and 3 years for different treatment duration thresholds (daily for 1–40 days and weekly for 1–26 weeks); number of prescriptions (1–15); and cumulative dose of the first episode of opioid use (50–2000 morphine milligram equivalents). Similarly, the relationship between the number of days’ supply, choice of first opioid prescription, and probability of continued opioid use at 1 and 3 years was also examined. Sensitivity analyses were conducted by modifying the discontinuation definition from ≥180 opioid-free days to ≥90 opioid-free days, changing the allowable gap in the first episode of opioid use from 30 days to 7 days, and excluding patients whose average daily dose of the first prescription exceeded 90 morphine milligram equivalents.

A total of 1,294,247 patients met the inclusion criteria, including 33,548 (2.6%) who continued opioid therapy for ≥1 year. Patients who continued opioid therapy for ≥1 year were more likely to be older, female, have a pain diagnosis before opioid initiation, initiated on higher doses of opioids, and publically or self-insured, compared with patients who discontinued opioid use in <365 days (Table). Among persons prescribed at least 1 day of opioids, the probability of continued opioid use at 1 year was 6.0% and at 3 years was 2.9% (supplemental figure 1; https://stacks.cdc.gov/view/cdc/44182) (supplemental figure 2; https://stacks.cdc.gov/view/cdc/44550) with a median time to discontinuation of 7 days (supplemental figure 3; https://stacks.cdc.gov/view/cdc/44551). Approximately 70% of patients have an initial duration of opioids of ≤7 days and 7.3% were initially prescribed opioids for ≥31 days. The largest incremental increases in the probability of continued opioid pain reliever use were observed when the first prescription supply exceeded 10 or 30 days (Figure 1), when a patient received a third prescription (Figure 2), or when the cumulative dose was ≥700 morphine milligram equivalents (supplemental figure 4; https://stacks.cdc.gov/view/cdc/44552). Substantial increases in probabilities of continued opioid use occurred when the initial duration reached 6 and 31 days (supplemental figure 2; https://stacks.cdc.gov/view/cdc/44550); the findings of the sensitivity analyses were similar (supplemental figures 5–10; https://stacks.cdc.gov/view/cdc/44183).

The highest probabilities of continued opioid use at 1 and 3 years were observed among patients who initiated treatment with a long-acting opioid (27.3% at 1 year; 20.5% at 3 years), followed by those whose initial treatment was with tramadol (13.7% at 1 year; 6.8% at 3 years) or a Schedule II short-acting opioid other than hydrocodone or oxycodone (8.9% at 1 year; 5.3% at 3 years) (supplemental table; https://stacks.cdc.gov/view/cdc/44181). The probabilities of continued opioid use at 1 and 3 years for persons starting on hydrocodone short acting (5.1% at 1 year; 2.4% at 3 years), oxycodone short-acting (4.7% at 1 year; 2.3% at 3 years), or Schedule III–IV (5.0% at 1 year; 2.2% at 3 years) opioids were similar (supplemental table; https://stacks.cdc.gov/view/cdc/44181).