title: New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation.
abstract: Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely, other studies, not accounting for duration, found that higher MED increased probability of depressive symptoms. To determine whether rate of MED increase is associated with NOD, a retrospective cohort analysis of Veterans Health Administration data (2000-2012) was conducted. Eligible patients were new, chronic (>90 days) opioid users, aged 18 to 80, and without depression diagnoses for 2 years before start of follow-up (n = 7051). Mixed regression models of MED across follow-up defined 4 rate of dose change categories: stable, decrease, slow increase, and rapid increase. Cox proportional hazard models assessed the relationship of rate of dose change and NOD, controlling for pain, duration of use, maximum MED, and other confounders using inverse probability of treatment-weighted propensity scores. Incidence rate for NOD was 14.1/1000PY (person-years) in stable rate, 13.0/1000PY in decreasing, 19.3/1000PY in slow increasing, and 27.5/1000PY in rapid increasing dose. Compared with stable rate, risk of NOD increased incrementally for slow (hazard ratio = 1.22; 95% confidence interval: 1.05-1.42) and rapid (hazard ratio = 1.58; 95% confidence interval: 1.30-1.93) rate of dose increase. Faster rates of MED escalation contribute to NOD, independent of maximum dose, pain, and total opioid duration. Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression. Clinicians should avoid rapid dose increase when possible and discuss risk of depression with patients if dose increase is warranted for pain.
authors.affiliation: Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.|Harry S. Truman Veterans Administration Medical Center, Columbia, MO, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Salas
authors.affiliation: Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.|Harry S. Truman Veterans Administration Medical Center, Columbia, MO, USA.|Saint Louis University Center for Outcomes Research, St. Louis, MO, USA.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Scherrer
authors.affiliation: Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Frank David
authors.initials: FD
authors.lastname: Schneider
authors.affiliation: Department of Psychiatry and Behavioral Health, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sullivan
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Bucholz
authors.affiliation: Saint Louis University Center for Outcomes Research, St. Louis, MO, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Burroughs
authors.affiliation: Center for Applied Health Research, Baylor Scott & White Health, and Central Texas Veterans Health Care System, Temple, TX, USA.|Texas A&M Health Science Center, Bryan, TX, USA.|UT Health Science Center, San Antonio, TX, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Copeland
authors.affiliation: Henry Ford Health System, Center for Health Policy and Health Services Research and Behavioral Health Services Detroit, MI, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Ahmedani
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.|The Bell Street Clinic, VA St. Louis Health Care System-John Cochran Division, St. Louis, MO, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lustman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects*; D016009:Chi-Square Distribution; D059350:Chronic Pain / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology*; D015331:Cohort Studies; D003863:Depression / Q000139:chemically induced* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D057286:Electronic Health Records / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D013997:Time Factors; D014481:United States; D014493:United States Department of Veterans Affairs; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid