A Preliminary Study of Stress, Mental Health, and Pain Related to the COVID-19 Pandemic and Odds of Persistent Prescription Opioid Use

Patient Recruitment

Participants were enrolled in the Prescription Opioids and Depression Pathways Cohort Study, henceforth termed the Pathways Study, which is designed to determine the mental health consequences of LTOT and risk factors for prescription opioid use disorder. The study protocol has been reported in detail.15 In brief, eligible patients were identified from the electronic health records of Saint Louis University’s academic medical practice in St. Louis, MO, and Henry Ford Health in Detroit, MI. Patients were eligible to enroll in the study if they were starting a new period of prescription opioid use, defined as no opioid use in the prior 3 months, and were free of cancer. Opioid use and cancer status were identified in electronic health records and confirmed in screening questions. Patients who completed the baseline assessment were invited to complete 6- and 12-month follow-up surveys. The current 6-month retention rate is approximately 82%. The present study uses data from the first 477 patients who completed baseline, 6-month follow-up assessments, and answered questions about COVID-19 stressors. Baseline enrollment began in November 2019. Measures of COVID-19-related stress were added to the 6-month follow-up survey in September 2020. Prior to incorporating the COVID-19 questions, 62 participants completed baseline. Therefore, the current study uses data from 477 participants who completed baseline and 6-month follow-up between September 2020 and January 2022.

All assessments were administered in REDCap and either completed by the subject on the internet or by a telephone interviewer entering answers into REDCap. Patients provided informed consent prior to participation. Patients were given a $50 gift card for each survey completed. All procedures were approved by Saint Louis University and Henry Ford Health’s Institutional Review Boards.

VariablesOutcome

Prescription opioid use at baseline and 6-month follow-up was based on self-report of the opioid type, frequency (daily vs. non-daily), and dose. Persistent opioid use was defined as using a prescription opioid at 6-month follow-up.

Primary Exposure

COVID-19-related stressors were derived from the Complementary and Integrative Research (CAIR) Pandemic Impact Questionnaire (C-PIQ).16 The C-PIQ measures experiences in the past 2 weeks and includes the following questions: (1) How much are you reading, watching, listening, talking or thinking about coronavirus/COVID-19? (2) How much do you worry about your health or the health of your friends or family? (3) How stressful have changes in social contacts, like family or friends, been for you? (4) How stressful have changes in your way of life, like changes in finances, education, living situation, childcare, etc. been for you? (5) How much has your mental/emotional health been worsened by the COVID-19 pandemic? We created a sixth question based on C-PIQ format which was as follows: (6) How much has your pain been worsened by the COVID-19 pandemic? For questions 1 and 2, binary (no/yes) variables were computed by combining response options never/rarely (no) vs. occasionally/often/most of the time (yes). Binary variables for questions 3 through 6 were created by combining response options not at all/ slightly (no) vs. moderately/very/extremely (yes).

Covariates

Demographic measures included age, race, gender, and marital status.

Pain Measures

The Brief Pain Inventory (BPI)17,18 measured pain site, severity, and pain interference. Participants reported whether they had pain in 17 different body locations (e.g., neck, lower back, upper back, legs etc.) which was used to define number of pain sites. Pain severity was measured via 4-items: worst in last 30 days, least in last 30 days, pain on average, and current pain. Pain severity was the average of these 4-items on a scale from “0=no pain” to “10=pain as bad as you can imagine.” Seven pain interference questions assessed whether pain has interfered with general activity, mood, walking ability, normal work, relationships, sleep, and enjoyment of life in the last 30 days. The pain interference score was the average of these 7-items on a scale of “0=does not interfere” to “10=completely interferes.”

Prescription Opioid Measures

We adjusted for baseline morphine equivalent dose (MME) and the baseline score on the Prescribed Opioids Difficulty scale (PODS).19 We used only the baseline MME and PODS because patients no longer using opioids at 6-month follow-up did not receive these assessments in follow-up surveys. The PODS measures psychosocial problems and concerns about opioid use. Higher scores indicate greater problems with opioids with scores ≥ 16 considered high.

Mental Health Measures

Mental health measures included generalized anxiety measured via the GAD-7, anhedonia measured via the Snaith-Hamilton Pleasure Scale (SHAPS) and vital exhaustion measured using the Maastricht Vital Exhaustion brief form. The GAD-7 measures general anxiety with higher scores indicating worse anxiety and a score ≥ 15 indicating severe anxiety.20 The SHAPS measures anhedonia with higher scores indicating more severe anhedonia. A score ≥ 3 indicates high anhedonia.21 Vital exhaustion is a measure of “unusual fatigue, increased irritability and feelings of demoralization,” and higher scores indicate worse vital exhaustion. A score of ≥10 indicates high vital exhaustion.22

Social Support and Date of Survey Completion

The PROMIS SF v2.0–Emotional Support 4a scale measured emotional support.23 Higher scores indicate more social support. Using ≥60 as a cut-off, we dichotomized the measure into low and high social support. Last, because the pandemic has waxed and waned, we controlled for the following time periods when surveys were completed: 3/2/20–12/31/20, 1/1/21–11/1/21, 11/2/21–present, or unknown. Measures obtained from baseline and 6-month follow-up are shown in Fig. 1.

Figure 1figure 1

Timing of assessments used in present study.

Analytic Approach

Change scores were computed for pain severity, pain interference, number of pain sites, generalized anxiety, anhedonia, vital exhaustion, and emotional support by subtracting baseline scores from 6-month scores. Therefore, a change score of 1-point represents an increase from baseline to 6-month follow-up. For all measures, except emotional support, decreasing scores represent improvement. All other covariates were measured at baseline only.

Analyses were performed with SAS v9.4 (SAS Institute, Cary, NC) at an alpha level of 0.05. A repeated measures difference-in-difference analysis, using a 2 (baseline, 6-month) × 2 (persist, stop) factorial repeated measures ANOVA for each pain, mental health, and social support variable, was conducted to assess whether change in these variables from baseline to 6-month follow-up is different based on whether patients persisted or stopped opioid use (see e-Table 1).

Bivariate Analyses

Chi-square tests estimated the bivariate association of each COVID-19 item and persistent opioid use at 6-month follow-up. Separate, bivariate logistic regression analyses estimated the association between COVID-19 stressors, demographics, change in pain measures, baseline MME and baseline PODS and change in mental health measures and persistent opioid use using odds ratios and 95% confidence intervals.

Multivariate Analyses

Multivariate logistic regression models estimated the association between COVID-19 stressors and odds of persistent opioid use. Subsequent models first adjusted for demographic variables, then change in pain variables, followed by adjustment for baseline MME and baseline PODS and change in mental health and social support measures. A fully adjusted model included all covariates. The associations between COVID-19 items, covariates, and persistent opioid use were expressed as odds ratios with 95% confidence intervals. Collinearity was evaluated by computing the variance inflation factor (VIF) and tolerance, both of which revealed no evidence of collinearity.

Sensitivity Analyses

Persistent opioid use may include a mix of intermittent and daily opioid users. To determine if COVID-19-related stressors were more strongly associated with persistent daily vs. persistent non-daily opioid use, we computed a fully adjusted multivariate, multinomial model. The primary outcome was no opioid use, non-daily opioid use, and daily opioid use at 6-month follow-up.

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