Funder: NIH, NIDA
Grant Number: R01ActDA043811
Grant Period: 4/1/2019 – 3/31/2023
Narrative: 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.
Lead Site: St. Louis University (PI Jeffrey Scherrer)
Participating Sites: HFHS (Site PI Brian Ahmedani)