Pathways from Chronic Prescription Opioid Use to New Onset Mood Disorder

Project Name:
Pathways from Chronic Prescription Opioid Use to New Onset Mood Disorder
Principal Investigator:
Jeffrey F. Scherrer, PhD
Principal Investigator Contact Information:         
Principal Investigator Institution:
Saint Louis University School of Medicine
Funding Period:
Funded 4/1/2019 – 3/31/2023
Research on the association between psychopathology and prescription opioid analgesic use (OAU) has established that mental illness influences risk of chronic OAU (i.e. >90-days), high dose OAU and misuse. We explored the reverse direction of association and found longer OAU and higher opioid doses are associated with increased risk of new onset depression (NOD), independent of pain. Using Veterans Health Affairs (VA) patient data revealed >90-day OAU was associated with a 35% (in VA patients) to 105% (in private sector patients) increased risk of NOD compared to patients with 1-30 day OAU. Our additional studies revealed that OAU is associated with depression recurrence and treatment resistant depression. If these results are confirmed in the present proposal, results have potential to greatly inform interventions to reduce chronic OAU (e.g. treating depression), elucidate pathways to OAU misuse, and generate a body of evidence that informs safe opioid prescribing. To reveal pathways from OAU to NOD and related depression phenotypes (i.e. dysthymia, bipolar, anhedonia, vital exhaustion) we must measure the patients’ pre-existing risk factors and post-OAU events. We will obtain diagnoses and symptom level data and covariates that are not available in the medical record data used in our R21 and strengthen the temporal relationships between OAU and NOD. The central hypothesis driving this research is that pre-OAU risk factors such as a history of depression and post-OAU events such as onset of opioid misuse contribute to NOD.
If NOD is explained by OAU alone and not by pre-existing risk factors, then the opioid epidemic is generating new cases of depression in a large population of middle-aged adults, otherwise not at risk for NOD. Findings will disentangle consequences or correlates of chronic pain per se from those of chronic, high dose OAU. We test whether the OAU-NOD association is moderated by pre-existing depression, substance use disorder (SUD), including opioid use disorder and trauma exposure. We next propose that post-OAU opioid misuse, SUD, poor functioning, low social support and poor sleep quality promote NOD. Using 12 monthly brief assessments, we will determine if change in OAU, independent of change in pain influences, depression trajectories and determine if there is a reciprocal relationship among these variables over time. We will determine if OAU is associated with different depression phenotypes and last determine which subtypes of depression contribute to incident opioid use disorder.
Grant Number:
Participating Sites:
Saint Louis University School of Medicine
Kaiser Permanente Washington
Henry Ford Health System
Jeffrey Scherrer, PhD
Brian Ahmedani, PhD
Lynn Debar, PhD
Major Goals:
In several studies controlling for pain, we found long term, > 90-day opioid analgesic use (OAU) is associated with increased risk for depression and impairs depression treatment and recovery. This project collects data from 1,500 patients using prescription opioids to determine the risk factors, (e.g. lifetime history of depression, substance use disorder, poor functioning), that may increase risk of OAU related depression. We characterize the type of depression most strongly associated with OAU and determine depression subtypes associated with incident opioid misuse and abuse. Our results will help clinicians educate patients and provide evidence to further encourage pain patients to limit OAU as much as possible to improve their mood and quality of life. Aim 1: Determine if patients with pre-OAU depression, substance use disorder (SUD), or trauma exposure, have a greater risk of a new post-OAU depression compared to those without a history of these conditions after controlling for sociodemographics, generalized anxiety disorder, pain severity, pain functioning, sleep, depression treatment and social support.Aim 2: Determine if post-OAU events (i.e. alcohol, illicit drug, or opioid misuse, or worse pain functioning or low social support or poor sleep quality) are more likely to develop NOD after controlling for OAU duration, pre-OAU depression, SUD, trauma and other confounding factors.Aim 3: Using 12 brief monthly assessments, determine which patterns of co-developing pain (severity/function) and opioid dose trajectories are associated with increasing, decreasing, stable and no depression symptoms.Aim 4: Determine if patients with >90-day OAU vs. ≤90-day OAU have significantly different associations with NOD symptom profiles, depression comorbidity profiles and types of depression (e.g. anhedonia, dysthymia, vital exhaustion).Aim 5. Determine which depression symptom profiles, depression comorbidity profiles and types of depression (e.g. anhedonia, dysthymia, vital exhaustion) in patients with >90-day OAU are most strongly associated with incident opioid misuse and opioid use disorder.
Description of study sample:
We will survey 1,500 non-cancer, chronic pain patients entering a new (i.e. no OAU in the past 6 months) period of continuous OAU. We target enrollment of 30-day users with an opioid refill allowing them to become 60-day users. Based on our research, of those who reach 60 days of OAU, 48%-66% become > 90-day users and have 35% to 105% increased risk for depression.6 We will collect comprehensive assessments at baseline, wave 2 (6-month follow-up), and wave 3 (12-month follow-up) and separate monthly brief assessments of OAU, pain, functioning and depression.
Current Status:
Study Registration:
Lessons Learned:
What’s next?