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

BACKGROUND: The COVID-19 pandemic has been associated with increased opioid prescribing. It is not known if perceived COVID-19 related stress is associated with increased odds of long-term opioid use. OBJECTIVE: To determine if greater COVID-19-related stress and worsening pain attributed to the pandemic was associated with LTOT over a 6-month observation period. DESIGN: Longitudinal cohort. PARTICIPANTS: Patients (n=477) from two midwestern health care systems, with any acute or chronic non-cancer pain, starting a new period of 30-90-day prescription opioid use, were invited to participate in the Prescription Opioids and Depression Pathways Cohort Study, a longitudinal survey study of pain, opioid use, and mental health outcomes. MAIN MEASURES: Baseline and 6-month follow-up assessments were used to measure the association between perceived COVID-19 stressors, the perception that pain was made worse by the pandemic and the odds of persistent opioid use, i.e., remaining a prescription opioid user at 6-month follow-up. Multivariate models controlled for demographics, opioid dose, and change in pain characteristics, mental health measures, and social support. KEY RESULTS: Participants were, on average, 53.9 (±11.4) years of age, 67.1% White race, and 70.9% female. The most frequently endorsed COVID-19 stressor was "worry about health of self/others" (85.7% endorsed) and the least endorsed was "worsened pain due to pandemic" (26.2%). After adjusting for all covariates, "worsened pain due to pandemic" (OR=2.88; 95%CI: 1.33-6.22), change in pain interference (OR=1.20; 95%CI: 1.04-1.38), and change in vital exhaustion (OR=0.90; 95%CI: 0.82-0.99) remained significantly associated with persistent opioid use. CONCLUSIONS: Patients who attribute worsening pain to the COVID-19 pandemic are more likely to be persistent opioid users. Further research is warranted to identify mechanisms underlying this association. Clinicians may consider discussing pain in the context of the pandemic to identify patients at high risk for persistent opioid use.

PTSD symptom improvement and smoking cessation among a sample of veterans.

Context: Poor health behaviors are common in persons with posttraumatic stress disorder (PTSD). PTSD symptom improvement has been followed by better health behaviors such as medication adherence and use of nutrition, weight loss, and substance abuse treatment programs. Whether PTSD improvement is associated with smoking cessation is uncertain. Objective: To determine if patients with, compared to without, clinically meaningful improvement (≥20 points vs. <20 points) in PTSD Checklist (PCL) scores are more likely to stop smoking. Study Design: Retrospective cohort using entropy balancing to control for confounding in Cox proportional hazard models overall and stratified by depression and alcohol abuse/dependence. Dataset: Veterans Health Affairs (VHA) medical record data from 2008-2015. Population studied: Patients aged 18-70 years with PTSD who had ≥ 1 visit to PTSD specialty care with a PCL score ≥50, at least one PCL score from ≥8 weeks to 12 months following first PCL≥50 ('exposure year'), and persistent smokers in the exposure year (n=449). Index date is the end of the exposure year. Intervention/Instrument: Change from first to last PCL score in exposure year classified as clinically meaningful vs. less than clinically meaningful improvement (≥20 point decrease vs. <20 point decrease). Outcome measures. Time to smoking cessation as documented in VHA administrative medical record data in the 2-years after index. Follow-up time was measured as months from index to either smoking cessation or censoring. Results: Overall, patients were 39.4 (±12.9) years old, 71.5% white, 86.6% male, 19.8% had a clinically meaningful PCL score decrease, and 32.7% quit smoking in the 2-years after index. After entropy weighting, PCL decrease ≥ 20 vs. < 20 was associated with a 57% increased likelihood of smoking cessation (HR=1.57; 95% CI=1.04-2.36). The relationship of PTSD improvement with smoking cessation was similar in patients with vs. without depression and with and without alcohol abuse/dependence. Among patients who quit smoking, about half remained non-smokers in the 12-months after initial quit date. Conclusions: A clinically meaningful reduction in PTSD symptoms was associated with smoking cessation in the 2-years after PTSD improvement. Not all patients with PTSD have access to PTSD treatment modalities that integrate smoking cessation therapy; however, PTSD treatment alone may improve patient self-efficacy and enable smoking cessation.

Increased Smoking Cessation Among Veterans With Large Decreases in Posttraumatic Stress Disorder Severity.

INTRODUCTION: Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. AIMS AND METHODS: Veterans Health Affairs (VHA) medical record data (2008-2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. RESULTS: On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04-2.36). CONCLUSIONS: Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. IMPLICATIONS: Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

Characteristics of Patients with Non-Cancer Pain and Perceived Severity of COVID-19 Related Stress.

Synopsis Patients with non-cancer pain reported increased pain and pain interference during the first months of the COVID-19 pandemic. We determined if pain, prescription opioid use, and comorbidities were associated with perceived COVID-19-related stress as the pandemic peaked. Analysis of survey data revealed that depression/anxiety, pain severity, and pain interference were most strongly and consistently associated with greater stress due to COVID-19 related changes in lifestyle, worsening of emotional/mental health and worsening pain. Identifying specific stressful experiences that most impacted patients with non-cancer pain may help target public health and treatment interventions. Background: During the first months of the COVID-19 pandemic, patients with chronic pain reported increased pain severity and interference. This study measured the association between pain, prescription opioid use, and comorbidities with perceived COVID-19-related stress as the pandemic peaked in the United States. Methods: From 9/2020 to 3/2021, the first 149 subjects from a prospective cohort study of non-cancer pain, completed a survey which contained the Complementary and Integrative Research (CAIR) Pandemic Impact Questionnaire (C-PIQ). Respondents also reported whether the pandemic has contributed to their pain or opioid use. Bivariate comparisons explored patient characteristics with each CAIR domain. Results: Respondents mean age was 54.6 (±11.3) years, 69.8% were female, 64.6% were White. Respondent characteristics were not associated with reading/watching/thinking about the pandemic or with worry about health. Depression/anxiety (p=0.003), using any prescription opioid in the prior three months (p=0.009), higher morphine milligram equivalent used (p=0.005), higher pain severity (p=0.011), and higher pain interference (p=0.0004) were all positively and significantly associated with moderate to severe stress due to COVID-19 related lifestyle changes. Depression/anxiety, pain severity, and pain interference were positively associated with COVID-19-related worsening emotional/mental health. Depression/anxiety were significantly (p<0.0001) associated with reporting that the pandemic made their pain worse. Conclusion: Depression, anxiety, pain severity, and pain interference were most strongly and consistently associated with COVID-19 changes in way of life, worsening of emotional/mental health, and worsening pain. Identifying specific stressful experiences that most impacted patients with noncancer pain may inform public health and treatment interventions.

A Trial of Sertraline or Cognitive Behavior Therapy for Depression in Epilepsy.

OBJECTIVE: Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS: We randomly assigned 140 adult outpatients with epilepsy and current major depressive disorder to sertraline or weekly CBT for 16 weeks. The primary outcome was remission from depression based on the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) seizure rates, the Adverse Events Profile (AEP), the Beck Depression Inventory, and MINI Suicide Risk Module. RESULTS: In the intention-to-treat analysis, 38 (52.8%; 95% confidence interval [CI] = ±12) of the 72 subjects assigned to sertraline and 41 (60.3%; 95% CI = ±11.6) of the 68 subjects in the CBT group achieved remission; the lower bound of efficacy for both groups was greater than our historical placebo control group upper bound of 33.7%. Difference in time to remission between groups was 2.8 days (95% CI = ±0.43; p = 0.79). The percent improvement of mean QOLIE-89 scores was significant for both the CBT (25.7%; p < 0.001) and sertraline (28.3%; p < 0.001) groups. The difference in occurrence of generalized tonic-clonic seizures between groups was 0.3% (95% CI = ±8.6; p = 0.95). Suicide risk at final assessment was associated with persistent depression (p < 0.0001) but not seizures or sertraline. INTERPRETATION: Depression remitted in just over one-half of subjects following sertraline or CBT. Despite the complex psychosocial disability associated with epilepsy, improving depression benefits quality of life. Serotonin reuptake inhibition does not appear to increase seizures or suicidality in persons with epilepsy. ANN NEUROL 2019;86:552-560.

Impact of adherence to antidepressants on long-term prescription opioid use cessation.

BACKGROUND: Depression contributes to persistent opioid analgesic use (OAU). Treating depression may increase opioid cessation. Aims To determine if adherence to antidepressant medications (ADMs) v. non-adherence was associated with opioid cessation in patients with a new depression episode after >90 days of OAU. METHOD: Patients with non-cancer, non-HIV pain (n = 2821), with a new episode of depression following >90 days of OAU, were eligible if they received ≥1 ADM prescription from 2002 to 2012. ADM adherence was defined as >80% of days covered. Opioid cessation was defined as ≥182 days without a prescription refill. Confounding was controlled by inverse probability of treatment weighting. RESULTS: In weighted data, the incidence rate of opioid cessation was significantly (P = 0.007) greater in patients who adhered v. did not adhered to taking antidepressants (57.2/1000 v. 45.0/1000 person-years). ADM adherence was significantly associated with opioid cessation (odds ratio (OR) = 1.24, 95% CI 1.05-1.46). CONCLUSIONS: ADM adherence, compared with non-adherence, is associated with opioid cessation in non-cancer pain. Opioid taper and cessation may be more successful when depression is treated to remission. Declaration of interest None.

The influence of prescription opioid use duration and dose on development of treatment resistant depression.

Long-term prescription opioid use is associated both with new-onset and recurrence of depression. Whether chronic opioid use interferes with depression management has not been reported, therefore we determined whether patients' longer duration of opioid use and higher opioid dose are associated with new-onset treatment resistant depression (TRD) after controlling for confounding from pain and other variables. Data was obtained from Veteran Health Administration (VHA) de-identified patient medical records. We used a retrospective cohort design from 2000-2012. Eligible subjects (n=6169) were 18-80years of age, free of cancer and HIV, diagnosed with depression and opioid-free for the 24-month interval prior to the observation period. Duration of a new prescription for opioid analgesic was categorized as 1-30days, 31-90days and >90days. Morphine-equivalent dose (MED) during follow-up categorized as ≤50mg versus >50mg per day. Pain and other sources of confounding were controlled by propensity scores and inverse probability of treatment weighting. Cox proportional hazard models were computed to estimate the association between duration and dose of opioid and onset of TRD. After controlling for confounding by weighting data, opioid use for 31-90days and for >90days, compared to 1-30days, was significantly associated with new onset TRD (HR=1.25; 95% CI: 1.09-1.45 and HR=1.52; 95% CI: 1.32-1.74, respectively). MED was not associated with new onset TRD. The risk of developing TRD increased as time spent on opioid analgesics increased. Long-term opioid treatment of chronic pain may interfere with treatment of depression.

Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations.

PURPOSE: Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid analgesic use is a function of the dose prescribed or the duration of use or both. METHODS: Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott & White Health (BSWH) and the Henry Ford Health System (HFHS). Patients (70,997 VHA patients, 13,777 BSWH patients, and 22,981 HFHS patients) were new opioid users, aged 18 to 80 years, without a diagnosis of depression at baseline. Opioid analgesic use duration was defined as 1 to 30, 31 to 90, and more than 90 days, and morphine equivalent dose (MED) was defined as 1 to 50 mg/d, 51 to 100 mg/d, and greater than 100 mg/d of analgesic. Pain and other potential confounders were controlled for by inverse probability of treatment-weighted propensity scores. RESULTS: New-onset depression after opioid analgesic use occurred in 12% of the VHA sample, 9% of the BSWH sample, and 11% of the HFHS sample. Compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use. Risk of new-onset depression with 31 to 90 days of opioid analgesic use ranged from hazard ratio [HR] = 1.18 (95% CI, 1.10-1.25) in VHA to HR = 1.33 (95% CI, 1.16-1.52) in HFHS; in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26-1.44) in VHA to HR = 2.05 (95% CI, 1.75-2.40) in HFHS. Dose was not significantly associated with a new onset of depression. CONCLUSIONS: Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood.

New depression diagnosis following prescription of codeine, hydrocodone or oxycodone.

PURPOSE: Longer duration of prescription opioid use is associated with risk of major depression after controlling for daily morphine equivalent dose and pain. It is not known if risk of depression varies as a function of the type of opioid prescribed. METHODS: A retrospective cohort design was used to model onset of new depression diagnosis among 11 462 Veterans Health Administration (VA) patients who were prescribed only codeine, only hydrocodone or only oxycodone for >30 days. Patients were free of prevalent opioid use and depression at baseline (2000-2001). Follow-up was 2002-2012. Propensity scores and weighting were used to balance covariates across opioid type. Cox-proportional hazard models were computed, using weighted data and additional adjustment for morphine equivalent dose (MED), duration of use, and pain after opioid initiation, to estimate the risk of new depression diagnosis among patients prescribed only codeine, only oxycodone vs. those prescribed only hydrocodone. RESULTS: After controlling for confounding, we observed that patients prescribed codeine, compared to hydrocodone, were significantly more likely to have a new depression diagnosis (HR = 1.27; 95%CI: 1.12-1.43). Oxycodone was significantly associated with onset of new depression diagnosis when exposure was modeled as total days exposed in post-hoc analysis, but not when exposure was duration of incident period of use. CONCLUSIONS: Although codeine is a less potent opioid, after controlling for MED, chronic use of this agent is associated with nearly a 30% greater risk of depression compared to hydrocodone. Additional research is needed to determine the mechanisms for this association. Copyright © 2016 John Wiley & Sons, Ltd.

Antidepressant medication use and glycaemic control in co-morbid type 2 diabetes and depression.

OBJECTIVE: Depression is prevalent in diabetes and is associated with increased risks of hyperglycaemia, morbidity and mortality. The effect of antidepressant medication (ADM) on glycaemic control is uncertain owing to a paucity of relevant data. We sought to determine whether the use of ADM is associated with glycaemic control in depressed patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective cohort study (n = 1399) was conducted using electronic medical record registry data of ambulatory primary care visits from 2008 to 2013. Depression and type 2 diabetes were identified from ICD-9-CM codes; ADM use was determined from prescription orders; and glycaemic control was determined from measures of glycated haemoglobin (A1c). Good glycaemic control was defined as A1c < 7.0% (53 mmol/mol). Generalized estimating equations were used to determine the effect of depression and ADM use on glycaemic control. RESULTS: Good glycaemic control was achieved by 50.9% of depressed subjects receiving ADM versus 34.6% of depressed subjects without ADM. After adjusting for covariates, depressed patients receiving ADM were twice as likely as those not receiving ADM to achieve good glycaemic control (odds ratio = 1.95; 95% confidence interval: 1.02-3.71). CONCLUSIONS: In this retrospective cohort study of a large sample of primary care patients with type 2 diabetes, ADM use was associated with improved glycaemic control.

Racial differences in the association between nonmedical prescription opioid use, abuse/dependence, and major depression.

BACKGROUND: African Americans (AAs) have lower rates of depressive disorders and are less likely to receive opioid analgesics for chronic pain than whites. Given the evidence that prescription opioid use is associated with depression, we hypothesized that the opioid abuse/dependence and depression comorbidity would be less common among AAs compared with whites. METHODS: A cross-sectional secondary analysis of the public use files for the 2012 (n = 55,268) and 2013 (n = 55,160) National Survey on Drug Use and Health (NSDUH) was used to obtain past-year, DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria diagnoses of nonmedical prescription opioid use (NMPOU), abuse/dependence, and major depressive episode (MDE). Covariates included anxiety disorder, alcohol and illicit drug abuse/dependence, smoking, age, gender, education, marital status, health insurance, county urbanicity, and income. Logistic regression models estimating the association between opioid use and MDE were computed before and after adjusting for covariates and separately for AAs and whites. RESULTS: AAs and whites had similar past-year prevalence of NMPOU (3.5% vs. 3.7%) and abuse/dependence (0.7% vs. 0.9%). MDE was significantly more prevalent among whites (7.4% vs. 5.5%; P < .0001). Among whites, NMPOU and abuse/dependence were associated with MDE (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.12-1.64 and OR = 2.22, 95% CI = 1.67-2.94, respectively). Among AAs, there were no significant associations between NMPOU, abuse/dependence, and MDE (OR range: 0.80-0.95). CONCLUSIONS: In a nationally representative sample, co-occurrence of past-year depression, NMPOU, and abuse/dependence was determined in whites but not AAs. Additional research is needed to establish the contribution of pain and temporal relationships.

Association of anxiety disorders and depression with incident heart failure.

OBJECTIVE: Depression has been associated with increased risk of heart failure (HF). Because anxiety is highly comorbid with depression, we sought to establish if anxiety, depression, or their co-occurrence is associated with incident HF. METHODS: A retrospective cohort (N = 236,079) including Veteran's Administration patients (age, 50-80 years) free of cardiovascular disease (CVD) at baseline was followed up between 2001 and 2007. Cox proportional hazards models were computed to estimate the association between anxiety disorders alone, major depressive disorder (MDD) alone, and the combination of anxiety and MDD, with incident HF before and after adjusting for sociodemographics, CVD risk factors (Type 2 diabetes, hypertension, hyperlipidemia, obesity), nicotine dependence/personal history of tobacco use, substance use disorders (alcohol and illicit drug abuse/dependence), and psychotropic medication. RESULTS: Compared with unaffected patients, those with anxiety only, MDD only, and both disorders were at increased risk for incident HF in age-adjusted models (hazard ratio [HR] = 1.19 [ 95% confidence interval {CI} = 1.10-1.28], HR = 1.21 [95% CI = 1.13-1.28], and HR = 1.24 [95% CI = 1.17-1.32], respectively). After controlling for psychotropics in a full model, the association between anxiety only, MDD only, and both disorders and incident HF increased (HRs = 1.46, 1.56, and 1.74, respectively). CONCLUSIONS: Anxiety disorders, MDD, and co-occurring anxiety and MDD are associated with incident HF in this large cohort of Veteran's Administration patients free of CVD at baseline. This risk of HF is greater after accounting for protective effects of psychotropic medications. Prospective studies are needed to clarify the role of depression and anxiety and their pharmacological treatment in the etiology of HF.

Prescription opioid analgesics increase the risk of depression.

BACKGROUND: Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations. OBJECTIVE: The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression. DESIGN: Retrospective cohort study, new user design. PATIENTS: Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000. MAIN MEASURES: Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007. KEY RESULTS: Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90-180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05-1.46 for 90-180 days, and HR = 1.51; 95 % CI:1.31-1.74 for > 180 days). CONCLUSIONS: In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.

Prescription Opioid Analgesics Increase Risk of Major Depression: New Evidence, Plausible Neurobiological Mechanisms and Management to Achieve Depression Prophylaxis.

More than 200 million prescriptions are written annually for opioid analgesics despite limited evidence of their long-term efficacy. These medications currently are prescribed to 10% - 15% of Americans with use of long-acting opioids projected to double in the next three to four years. Despite this widespread use, little is known about the risks of opioids, particularly with chronic use. New data from our research group published in the Journal of General Internal Medicine provides clear evidence that prescription opioid used for non-cancer, non-HIV pain increases significantly the risk of development of major depressive disorder in opioid naïve individuals with no recent history of depression and substance used disorders. The risk of depression increased as the dose and/or the duration of opioid use increased. The purpose of the present paper is to elucidate the details of this study, to examine potential neurobiological mechanisms responsible for the depressogenic effect of opioid analgesics, and to discuss management options that emphasize depression prophylaxis.

Baseline Characteristics From a New Longitudinal Cohort of Patients With Noncancer Pain and Chronic Opioid Use in the United States.

Retrospective cohort studies have consistently observed that long-term prescription opioid use is a risk factor for new major depressive episodes. However, prospective studies are needed to confirm these findings and establish evidence for causation. The Prescription Opioids and Depression Pathways cohort study is designed for this purpose. The present report describes the baseline sample and associations between participant characteristics and odds of daily versus nondaily opioid use. Second, we report associations between participant characteristics and odds of depression, dysthymia, anhedonia, and vital exhaustion. Patients with noncancer pain were eligible if they started a new period of prescription opioid use lasting 30 to 90 days. Participants were 54.8 (standard deviation ± 11.3) years of age, 57.3% female and 73% White race. Less than college education was more common among daily versus nondaily opioid users (32.4% vs 27.3%; P = .0008), as was back pain (64.2% vs 51.3%; P < .0001), any nonopioid substance use disorder (12.8% vs 4.8%; P < .0001), and current smoking (30.7% vs 18.4% P < .0001). High pain interference (50.9% vs 28.4%; P < .0001) was significantly associated with depression, as was having more pain sites (6.9 ± 3.6 vs 5.7 ± 3.6; P < .0001), and benzodiazepine comedication (38.2% vs 23.4%; P < .0001). High pain interference was significantly more common among those with anhedonia (46.8% vs 27.4%; P < .0001), and more pain sites (7.0 ± 3.7 vs 5.6 ± 3.6; P < .0001) were associated with anhedonia. Having more pain sites (7.9 ± 3.6 vs 5.5 ± 3.50; P < .0001) was associated with vital exhaustion, as was back pain (71.9% vs 56.8%; P = .0001) and benzodiazepine comedication (42.8% vs 22.8%; P < .0001). Patients using prescription opioids for noncancer pain have complex pain, psychiatric, and substance use disorder comorbidities. Longitudinal data will reveal whether long-term opioid therapy leads to depression or other mood disturbances such as anhedonia and vital exhaustion. PERSPECTIVE: This study reports baseline characteristics of a new prospective, noncancer pain cohort study. Risk factors for adverse opioid outcomes were most common in those with depression and vital exhaustion and less common in dysthymia and anhedonia. Baseline data highlight the complexity of patients receiving long-term opioid therapy for noncancer pain.

Factors Associated With Interest in Engaging in Psychological Interventions for Pain Management.

OBJECTIVE: Engagement in evidence-based psychological interventions for pain management is low. Identifying characteristics associated with interest in interventions can inform approaches to increase uptake and engagement. The purpose of this study was to examine factors associated with interest in psychological interventions among persons with chronic noncancer pain receiving prescription opioids. METHODS: Participants with chronic noncancer pain and a new 30 to 90 day opioid prescription were recruited from 2 health systems. Participants (N=845) completed measures regarding pain, opioid use, psychiatric symptoms, emotional support, and interest in psychological interventions for pain management. RESULTS: There were 245 (29.0%) participants who reported a high interest in psychological interventions for pain management. In bivariate analyses, variables associated with interest included younger age, female sex, greater pain severity, greater pain interference, greater number of pain sites, lower emotional support, depression, anxiety, and post-traumatic stress disorder ( P <0.05). In a multivariate model, greater pain severity (odds ratio [OR]=1.17; CI: 1.04-1.32), depression (OR=2.10; CI: 1.39-3.16), post-traumatic stress disorder (OR=1.85; CI: 1.19-2.95), and lower emotional support (OR=0.69; CI: 0.5-0.97) remained statistically significant. DISCUSSION: The rate of interest in psychological interventions for pain management was low, which may indicate that patients initiating opioid treatment of chronic noncancer pain have low interest in psychological interventions. Greater pain severity and psychiatric distress were related to interest, and patients with these characteristics may especially benefit from psychological interventions. Providers may want to refer to psychological interventions before or when opioids are initiated. Additional work is needed to determine whether this would reduce long-term opioid use.

Characteristics of patients with non-cancer pain and long-term prescription opioid use who have used medical versus recreational marijuana.

OBJECTIVE: Marijuana use is increasingly common among patients with chronic non-cancer pain (CNCP) and long-term opioid therapy (LTOT). We determined if lifetime recreational and medical marijuana use were associated with more frequent and higher dose prescription opioid use. DESIGN: Cross-sectional SUBJECTS: Eligible patients (n=1,037), who had a new period of prescription opioid use lasting 30-90 days, were recruited from two midwestern health care systems to a study of long-term prescription opioid use and mental health outcomes. The present cross-sectional analyses uses baseline data from this on-going cohort study. METHODS: Primary exposures were participant reported lifetime recreational and medical marijuana use versus no lifetime marijuana use. Prescription opioid characteristics included daily versus non-daily opioid use and ≥50 morphine milligram equivalent (MME) dose per day vs. <50 MME. Multivariate, logistic regression models estimated the association between lifetime recreational and medical marijuana use vs. no use and odds of daily and higher dose prescription opioid use, before and after adjusting for confounding. RESULTS: The sample was an average of 54.9 (SD±11.3) years of age, 57.3% identified as female gender, 75.2% identified as White, and 22.5% identified as Black race. Among all participants, 44.4% were never marijuana users, 21.3% were recreational only, 7.7% medical only and 26.6% were both recreational and medical marijuana users. After controlling for all confounders, lifetime recreational marijuana use, as compared to no use, was significantly associated with increased odds of daily prescription opioid use (OR=1.61; 95%CI:1.02-2.54). There was no association between lifetime recreational or medical marijuana use and daily opioid dose. CONCLUSION: Lifetime medical marijuana use is not linked to current opioid dose, but lifetime recreational use is associated with more than a 60% odds of being a daily prescription opioid user. Screening for lifetime recreational marijuana use may identify patients with chronic pain who are vulnerable to daily opioid use which increases risk for adverse opioid outcomes. Prospective data is needed to determine how marijuana use influences the course of LTOT and vice versa.

Social support and the association between post-traumatic stress disorder and risk for long-term prescription opioid use.

ABSTRACT: Post-traumatic stress disorder (PTSD) is common in patients with chronic pain, adversely affects chronic pain outcomes, and is associated with opioid use and adverse opioid outcomes. Social support is a robust predictor of PTSD incidence and course as well as chronic pain outcome. We determined whether the association between PTSD and persistent opioid use was modified by emotional support in a cohort of patients receiving opioids for noncancer pain. Eligible participants were ≥18 years and had completed a new period of prescription opioid use lasting 30 to 90 days. Bivariate associations between cohort characteristics and each key variable was assessed using χ2 tests for categorical variables and t-tests for continuous variables. Interaction between PTSD and emotional support was assessed by a priori stratification on low vs high emotional support. Participants (n = 808) were 53.6 (SD ± 11.6) years of age, 69.8% female, 69.6% White, and 26.4% African American. Overall, 17.2% had probable PTSD. High emotional support was significantly (P < 0.0001) more common among those without probable PTSD. Prescription opioid use at 6-month follow-up was significantly (P = 0.0368) more common among patients with vs without probable PTSD. In fully adjusted models, PTSD was no longer associated with opioid use at 6-month follow-up among participants with high emotional support. Among those with lower emotional support, PTSD was significantly associated with opioid use at 6-month follow-up in unadjusted (odds ratio = 2.40; 95% confidence interval: 1.24-4.64) and adjusted models (odds ratio = 2.39; 95% confidence interval: 1.14-4.99). Results point to the hypothesis that improvement of emotional support in vulnerable patients with chronic pain and PTSD may help reduce sustained opioid use.

Witnessed versus unwitnessed random urine tests in the treatment of opioid dependence.

BACKGROUND AND OBJECTIVES: Clinics licensed to provide pharmacotherapy for opiate dependence disorder are required to perform random urine drug screen (RUDS) tests. The results provide the empirical basis of individual treatment and programmatic effectiveness, and public health policy. Patients consent to witnessed testing but most tests are unwitnessed. The purpose of the present study was to compare treatment effectiveness estimates derived from witnessed versus unwitnessed urine samples. METHODS: We adopted a policy requiring visually witnessed urine drug screens (WUDS) and studied its impact (a single group, pretest-posttest design) on the RUDS test results in 115 male veterans enrolled in the St. Louis VA Opioid Treatment Program. RESULTS: The percentage of opioid-positive urine samples increased significantly following implementation of WUDS (25% vs. 41%, χ(2) = 66.5, p < .001). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Results of this preliminary study suggest that random testing alone does not ensure the integrity of UDS testing. Outcome calculations based on random unwitnessed tests may overestimate the effectiveness of opioid dependence disorder treatment.

Severity of posttraumatic stress disorder, type 2 diabetes outcomes and all-cause mortality: A retrospective cohort study.

BACKGROUND: Some evidence suggests patients with comorbid PTSD and type 2 diabetes (T2D) have worse T2D outcomes than those with T2D alone. However, there is no evidence regarding PTSD severity and risk for starting insulin, hyperglycemia, microvascular complications, and all-cause mortality. METHODS: In this retrospective cohort study, Veterans Health Affairs (VHA) medical record data from fiscal year (FY) 2012 to FY2022 were used to identify eligible patients (n = 23,161) who had a PTSD diagnosis, ≥1 PTSD Checklist score, controlled T2D (HbA1c ≤ 7.5) without microvascular complications at baseline. PTSD Checklist for DSM-5 (PCL-5) scores defined mild, moderate, and severe PTSD. Competing risk and survival models estimated the association between PTSD severity and T2D outcomes before and after controlling for confounding. RESULTS: Most (70%) patients were ≥ 50 years of age, 88% were male, 64.2% were of white race and 17.1% had mild, 67.4% moderate and 15.5% severe PTSD. After control for confounding, as compared to mild PTSD, moderate (HR = 1.05; 95% CI:1.01-1.11) and severe PTSD (HR = 1.15; 95%CI:1.07-1.23) were significantly associated with increased risk for microvascular complication. Hyperarousal was associated with a 42% lower risk of starting insulin. Negative mood was associated with a 16% increased risk for any microvascular complication. Severe PTSD was associated with a lower risk for all-cause mortality (HR = 0.76; 95%CI:0.63-0.91). CONCLUSIONS: Patients with comorbid PTSD and T2D have an increased risk for microvascular complications. However, they have lower mortality risk perhaps due to more health care use and earlier chronic disease detection. PTSD screening among patients with T2D may be warranted.