Dissertation/Thesis Abstract

The Influence of Opioid Dose Escalation and Discontinuation on Pain Scores, Drug Overdoses, Substance Use Disorders, and Healthcare Utilization
by Hayes, Corey J., Ph.D., University of Arkansas for Medical Sciences, 2018, 412; 13421390
Abstract (Summary)

Chronic non-cancer pain (CNCP) is pervasive in the U.S. with approximately 20% of the population experiencing some form of pain that lasts at least 6 months. Chronic opioid use is common among those with CNCP with estimates of up to 30% among those with low back pain. During chronic opioid use, many patients transition to either higher doses, to intermittent use, or discontinue altogether. A better understanding of the effects of altering chronic opioid therapy is warranted. These studies used a longitudinal, retrospective cohort study design. Veterans with CNCP and chronic opioid use were identified. First (Specific Aim 1), Veterans who escalated (?20% increase) their doses were compared to those who maintained their doses (±20% change). Outcomes evaluated included Numeric Rating Scale pain scores and opioid-related adverse outcomes (AOs) including substance use disorders (SUDs). The primary analyses were conducted among a 1:1 greedy matched sample. Sensitivity analyses were conducted with stabilized inverse probability of treatment weighting and instrumental variable models. There were 32,420 dose maintainers and 20,767 dose escalators with 19,358 (93.2%) dose escalators matched to dose maintainers. Pain scores were persistently higher among dose escalators as compared to dose maintainers at each 90 day time point after the index date (0–90 Days After Index Date: Dose Escalators: 4.6779, 95% CI: 4.6395, 4.7166; Dose Maintainers: 4.3228, 95% CI: 4.2833, 4.3627, p < 0.0001; 91–180 Days After Index Date: Dose Escalators: 4.5313, 95% CI: 4.4925, 4.5705; Dose Maintainers: 4.2454, 95% CI: 4.2055, 4.2857, p < 0.0001) but were not different in the 90 days prior to the index date (Dose Escalators: 4.6430, 95% CI: 4.6046, 4.6818; Dose Maintainers: 4.5895, 95% CI: 4.5507, 4.6286, p = 0.0551). Composite AOs (OR = 1.311, 95% CI: 1.227, 1.401) and composite SUDs (OR = 1.311, 95% CI: 1.223, 1.406) were higher among dose escalators as compared to dose maintainers. Second (Specific Aim 2), Veterans who discontinued (180 days without opioid use) or switched to intermittent opioid use (less than 90 days of opioid use within a 180 day period) were compared to those Veterans who continued to use opioids chronically. Outcomes evaluated were the same as with Specific Aim 1 in addition to measures of service utilization (physical therapy, chiropractic care, pain clinic, primary care, and mental healthcare visits) and non-opioid medication use (antidepressants, benzodiazepines, skeletal muscle relaxants, non-opioid analgesics, hypnotics/non-benzodiazepine sedatives). The analytic approaches described in Aim 1 were also used for Aim 2. There were 58,927 Veterans continuing chronic opioid use, 40,184 switching to intermittent opioid use, and 7,225 who discontinued opioid use. A total of 37,170 (92.5%) intermittent opioid users matched to continued chronic users while 7,212 (99.8%) discontinuers matched. Small differences in average pain scores in the 90 days before the index date were seen between intermittent opioid users and continued chronic opioid users (Intermittent Opioid Users: 3.9445, 95% CI: 3.9158, 3.9733; Continued Chronic Opioid Users: 4.0330, 95% CI: 4.0045, 4.0618, p < 0.0001) and between discontinuers and continued chronic users (Discontinuers: 3.3785, 95% CI: 3.3148, 3.4435; Continued Chronic Opioid Users: 3.5256, 95% CI: 3.4625, 3.5898, p = 0.0014). Pain scores between the two groups diverge with intermittent opioid users and discontinuers reporting lower pain scores as compared to continued chronic users in each of the follow-up time periods (0–90 After Index Date: Intermittent Opioid Users: 3.7577, 95% CI: 3.7288, 3.7869; Continued Chronic Opioid Users: 4.0596, 95% CI: 4.0308, 4.0886, p < 0.0001; Discontinuers: 2.9674, 95% CI: 2.9036, 3.0326; Continued Chronic Opioid Users: 3.7507, 95% CI: 3.6856, 3.8169, p ≤ 0.0001; 91–180 Days After the Index Date: Intermittent Opioid Users: 3.7472, 95% CI: 3.7182, 3.7764; Continued Chronic Opioid Users: 3.9780, 95% CI: 3.9490, 4.0072, p < 0.0001; Discontinuers: 2.9141, 95% CI: 2.8500, 2.9796; Continued Chronic Opioid Users: 3.6895, 95% CI: 3.6238, 3.7563, p ≤ 0.0001). AOs were slightly higher among intermittent users (OR = 1.052, 95% CI: 1.002, 1.103) and lower among discontinuers (OR = 0.771, 95% CI: 0.686, 0.867) as compared to continued chronic users. SUDs were lower for intermittent users (OR = 0.919, 95% CI: 0.870, 0.971) as compared to continued chronic users. Pain clinic, primary care, and mental healthcare visits were similar between discontinuers and continued chronic users and intermittent users and continued chronic users before the transition; however, after transitioning, visit rates were lower for intermittent users and discontinuers. Each class of non-opioid medication use was lower for discontinuers as compared to continued chronic users; the same was true in comparing intermittent users to continued chronic users except for non-opioid analgesics which were higher (OR = 1.044, 95% CI: 1.003, 1.087). (Abstract shortened by ProQuest.)

Indexing (document details)
Advisor: MARTIN, Bradley C.
Commitee: Brown, Joshua, Hudson, Teresa J., Krebs, Erin E., Li, Chenghui
School: University of Arkansas for Medical Sciences
Department: Pharmaceutical Sciences
School Location: United States -- Arkansas
Source: DAI-B 80/08(E), Dissertation Abstracts International
Subjects: Pharmaceutical sciences
Keywords: Chronic opioid use, Discontinuation, Opioid dose escalation, Opioids
Publication Number: 13421390
ISBN: 978-1-392-00956-7
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