The length of time that a patient is put on prescription painkillers, and not the dosage level, is the biggest association with developing misuse problems, according to a population-level study of patients who underwent surgery and were prescribed opioids.

The more prescriptions written out and filled for patients means a gradually increasing risk factor for abuse and dependence, according to the study in the BMJ.

“Each refill and week or opioid prescription is associated with a large increase in opioid misuse among opioid naïve patients,” write the researchers, led by a group from Harvard Medical School. “The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period.”

The data involved 1 million people who had no experience with opioids who underwent surgery between 2008 and 2016 in the United States. (The data was from an administrative database at Aetna, an insurer involved in the research).

Just over half of those million were prescribed opioids after the procedures – 568,612 people. Of those, about one percent were eventually marked with a code for abuse in their records.

The prescription history was then cross-referenced with the people who had, and did not have, abuse problems. Variables included the amount of the drugs, and how long they were continued by the doctors’ prescriptions.

The outcome: the adjust risk of abuse went up 44 percent with each refill, and 20 percent with each additional week on the drugs.

They also tested the data over different years and within different states, to ensure that the trends hadn’t been affected by time period or geography. The effect of duration over dose appeared to have the same association across the board, they said.

“Our findings are important as they offer a potential lever for intervention and behavior change after surgery,” they conclude. “Clinicians are trapped between guidelines that recommend shorter duration and lower dosing of opioid drugs and a subset of patients who request or require opioids beyond the initial prescriptions.

“With these seemingly conflicting forces at play, our analysis provides a broad evidentiary framework to inform clinician behavior and promote protocol development,” they add.

More than 183,000 Americans died of opioid overdoses between 1999 and 2015, and the number continues to climb. Two studies published last year pointed to a trail of how the epidemic began decades ago: one pointed to a five-sentence letter published in The New England Journal of Medicine in 1980, which bolstered safety arguments for prescribing opiates for decades; the other found that one in 12 doctors in the United States are being paid by pharmaceutical companies on topics related to opioids, as they explained in the American Journal of Public Health last summer.