Many people have a euphoric response to opioid painkillers because of the effect they have on the brain regions involved in reward. But new research published in the Annals of Family Medicine suggests long-term use of this painkiller could increase the risk of developing new-onset depression.

The study revealed that more than 200 million prescriptions for opioids are written in the United States annually, with known consequences of their use including abuse and accidental overdose. But researchers found that the risk of depression — a less understood adverse outcome of opioid use — increases after 30 days of use.

"Opioid-related new onset of depression is associated with longer duration of use but not dose," Jeffrey Scherrer, lead author of the study, wrote in the study. "Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression."

Researchers collected and analyzed data from 70,997 Veterans Health Administration (VHA) patients, 13,777 Baylor Scott & White Health (BSWH) patients, and 22,981 patients from the Henry Ford Health System (HFHS). The patients, whose ages ranged from 18 to 80, were classified into three mutually exclusive opioid use duration groups within their respective health systems: one to 30 days, 31 to 90 days, and more than 90 days of a continuous supply. For the study, participants were considered continuous users if no gap of more than 30 days occurred between the end of one prescription and the start of another.

The opioids the participants used included codeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, oxycodone, oxymorphone, morphine, and pentazocine.

The study found that 12 percent of the VHA sample, 9 percent of the BSWH sample, and 11 percent of the HFHS sample had a new diagnosis for depression. They found that compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use across the three health care systems.

Among the VHA patients, 11.6 percent of 1- to 30-day users, 13.6 percent of 31- to 90-day users, and 14.4 percent of longer than 90-day users had new-onset depression. Among BSWH patients, cases of new-onset depression increased from 8.4 percent among one- to 30-day users to 10.6 percent for 31- to 90-day users to 19 percent among longer than 90-day users. In HFHS patients, cases of new-onset depression increased from 10.7 percent among one- to 30-day users to 14.8 percent with 31- to 90-day users to 19.3 percent for those who used the drug for more than 90 days..

"Findings were remarkably consistent across the three health care systems even though the systems have very different patient characteristics and demographics," Scherrer said. Opioid dose was not significantly associated with the onset of depression.

Researchers said the findings may be explained by the opioids' effects on the nervous system and testosterone levels after long-term use. The link between opioid use and depression "was independent of the known contribution of pain to depression," they wrote.

Source: Scherrer J, Sala J, Copeland L, et al. Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations. Annals of Family Medicine. 2016