Frequency of Use Increases Risk for Depression Among Long-Term Prescription Opioid Users

ST. LOUIS, MO - Reducing the frequency of opioid use in chronic opioid therapy may limit the risk for depression, a Saint Louis University School of Medicine study shows.

The study, “Long-term Prescription Opioid Users Risk New Onset Depression Increases with Frequency of Use,” published in Pain, the Journal of the International Association for the Study of Pain.

Jeffrey Scherrer, Ph.D., a professor in Family and Community Medicine at Saint Louis University, and his co-authors find that among chronic opioid uses, daily and near-day prescription opioid use is associated with a greater risk for new onset depression, compared to occasional use.

“In long-term opioid therapy, the risk for new depression episodes is up to 40 percent greater in near daily users, compared to occasional users,” said Scherrer, who is also the senior director of research for SLU’s AHEAD (Advanced HEAlth Data) Institute. “Patients could reduce depression risk by avoiding opioid use on as many low-pain days as possible.”

The study found the association for new onset depression in the large, nationally distributed patient cohort was independent of pain conditions, co-morbid psychiatric disorders physical conditions and demographics. The cohort was made available through a Research Growth Fund Award and SLU’s AHEAD Institute, both supported by SLU’s Research Institute.

Since 2012, the number of new opioid prescriptions in the United States has declined, however, between 2006-2017, the proportion of 30-day opioid prescriptions and the average duration of prescriptions increased.

Scherrer and his co-authors used de-identified patient data from 2010-2018 from a commercial integrated claims-clinical data set to create a cohort of 5,146 patients.

This study compared patients with a new period of long-term prescription opioid use who used opioids occasionally, intermittently, frequently and daily. New long-term opioid therapy was defined by more than 90 days of LTOT following a six-month period of being opioid free.

The cohort’s patients were aged 18-80 with a claim in the year before of long-term opioid therapy. They were required to be free of depression diagnoses for one year prior to the start of the new period of opioid use. Patients with cancer of HIV were excluded.

Opioid drugs in the study included codeine, dihydrocodeine, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, oxymorphone, pentazocine, tapentadol and tramadol.

“This work advances years of existing research that has established an association between long-term prescription opioid use and risk for depression by indicating a possible reason why some but not all long-term users develop depression,” Scherrer said.

The researchers recommended long-term prescription opioid users try to reduce the number of days they take their opioid medication to attenuate risk for depression as well as repeated screenings for depression during long-term opioid therapy.

Future research is needed, the authors say, to model the risk of depression using variables that are measured prospectively and map onto the measures applied in retrospective cohort studies. Such a study is currently being directed by Scherrer with data collection at SLU and the Henry Ford Health System.

Other authors include Joanne Salas, MPH, of the Department of Family and Community Medicine at Saint Louis University and SLU’s AHEAD Research Institute; Lisa R. Miller-Matero, Ph.D., Center for Health Policy and Health Services Research and Behavioral Health Services, Henry Ford Health System, Detroit, Mich.; Mark D. Sullivan, M.D., Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, Wash.; Jane C. Ballantyne, M.D., Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Wash.; Lynn Debar, Ph.D., Kaiser Permanente Washington Health Research Institute, Seattle, Wash.; Richard A. Grucza, Ph.D., Department of Family and Community Medicine at Saint Louis University and SLU’s AHEAD Research Institute; Patrick J. Lustman, Ph.D., Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo.; and Brian K. Ahmedani, Ph.D., Center for Health Policy and Health Services Research and Behavioral Health Services, Henry Ford Health System, Detroit, Mich.

An internal award to Scherrer from the Saint Louis University Research Institute provided support to obtain commercial medical record and claims data. The funder had no role in the design and conduct of the study.

AHEAD Institute

The Advanced HEAlth Data (AHEAD) Research Institute at Saint Louis University is a comprehensive center for data-driven innovation and research aimed at improving the health of individuals and populations. 

The institute brings together researchers from various fields and disciplines to help improve patient and population health, advance the quality of health care and decrease health care costs. The new institute will utilize and develop data resources; novel analytic methods; predictive modeling; machine learning; and integrated, wearable health devices and will collaborate with national research networks.

Saint Louis University School of Medicine

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.