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.

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.

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.

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.

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.

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.

Long-term prescription opioid users' risk for new-onset depression increases with frequency of use.

ABSTRACT: Long-term opioid therapy (LTOT) is associated with increased risk for depression. It is not known if the frequency of opioid use during LTOT is associated with new-onset depression. We used Optum's de-identified Integrated Claims-Clinical dataset (2010-2018) to create a cohort of 5146 patients, 18 to 80 years of age, with an encounter or claims in the year before new LTOT. New LTOT was defined by >90-day opioid use after remaining opioid free for 6 months. Opioid use frequency during the first 90 days of LTOT was categorized into occasional use (<50% days covered), intermittent use (50% to <80% days covered), frequent use (80% to <90% days covered), and daily use (≥90% days covered). Propensity scores and inverse probability of exposure weighting controlled for confounding in models estimating risk for new-onset depression. Patients were on average 54.5 (SD ± 13.6) years of age, 55.7% were female, 72.5% were White, and 9.5% were African American. After controlling for confounding, daily users (hazard ratio = 1.40; 95% confidence interval: 1.14-1.73) and frequent users (hazard ratio = 1.34; 95% confidence interval: 1.05-1.71) were significantly more likely to develop new-onset depression compared with occasional users. This association remained after accounting for the contribution of post-index pain diagnoses and opioid use disorder. In LTOT, risk for new depression episodes is up to 40% greater in near-daily users compared with occasional users. Patients could reduce depression risk by avoiding opioid use on as many low pain days as possible. Repeated screening for depression during LTOT is warranted.

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.

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.

Opioid dosing among patients with 3 or more years of continuous prescription opioid use before and after the CDC opioid prescribing guideline.

BACKGROUND: Opioid doses declined after the Centers for Disease Control (CDC) opioid prescribing guideline was published. However, it is unknown if dose declines occurred in patients with ≥ 3 years of continuous opioid use. METHODS: Optum® de-identified integrated Electronic Health Record and claims data were used to create an adult sample (n = 400) with continuous opioid use for 18 months before and after the guideline publication. Based on the morphine milligram equivalent (MME) distribution at Month 1, patients were categorized into 1-50, 51-100, 101-200, and >200 mg baseline MME. Interrupted time series analysis using segmented mixed linear regression models stratified on baseline MME estimated average monthly changes in MME in the 18-months pre- and post-guideline, before and after adjusting for time-varying pain conditions, psychiatric disorders and benzodiazepine prescription. RESULTS: Patients were 59.6 (SD±11.8) years of age, 55.8% female and 84.0% white race. For 1-50 MME, monthly dose slope was significantly (p<0.0001) flatter post-guideline (pre b = 0.34 MME/month vs. post b = 0.12 MME/month). For 51-100 MME, the pre- and post-guideline dose slopes did not significantly differ (pre b = 0.60 MME/month vs. post b = 0.27 MME/month). For 101-200 MME, post-guideline dose slope was significantly (p<0.0001) steeper and decreasing post-guideline (pre b = 0.11 MME/month vs. post b= -1.33 MME/month). Among >200 MME, dose decreased in the pre- and post-guideline periods, and post-guideline decline was significantly (p<0.0001) steeper (b= -1. 86 MME/month vs. b= -4.13 MME/month). CONCLUSIONS: Among patients on multiyear opioid therapy, the CDC guideline was associated with a modest change in dosing, except for patients on very high doses. The guideline was not associated with decreasing MME among lower-dose, long-term users.

Depression and Buprenorphine Treatment in Patients with Non-cancer Pain and Prescription Opioid Dependence without Comorbid Substance Use Disorders.

BACKGROUND: Depression occurs in 40% of patients with prescription opioid dependence (POD). Existing studies of the association between depression and buprenorphine (BUP) treatment for POD are inconsistent and often include patients with comorbid substance use disorders (SUD). We estimated the association between depression and BUP use in patients with pain and POD and free of comorbid SUD. METHODS: Optum® de-identified Electronic Health Record dataset from 2010 to 2018 was used to identify 5,529 patients with chronic pain, with and without depression, receiving prescription opioids and free of substance use disorder diagnoses for one year before POD diagnoses. Unadjusted and adjusted Cox proportional hazard models and negative binomial regression models were computed to estimate the association between depression and time to BUP start, number of BUP prescriptions in the year after BUP start and time to >30 day BUP gap. RESULTS: Patients' mean age was 52.4 (SD±15.3) years, 62% were female and 84% were white and 4.9% (n=270) started BUP. Depression was not associated with BUP initiation.. Among BUP starters, depression vs. no depression, was significantly associated with receiving 29% fewer BUP prescriptions (RR=0.71; 95%CI: 0.51-0.98) and an increased risk for > 30 day gap (HR=1.76; 95%CI:1.01-3.09). LIMITATIONS: Missing data prevented measuring BUP dose. CONCLUSIONS: Depression is likely associated with earlier BUP treatment dropout. Depression related medication non-adherence or possible worsening of depression following BUP taper could explain results. Research is needed to determine if depression severity is associated with BUP dose trajectories and multi-year BUP retention..

PTSD improvement and substance use disorder treatment utilization in veterans: Evidence from medical record data.

BACKGROUND: Clinical trials reveal posttraumatic stress disorder (PTSD) improvement leads to decreased substance use among patients with comorbid substance use disorder (SUD). Using administrative medical record data, we determined whether clinically meaningful PTSD Checklist (PCL) (≥20 points) score decreases were positively associated with SUD treatment utilization. METHODS: We used a retrospective cohort of Veterans Health Affairs (VHA) medical record data (2008-2015). PTSD Checklist (PCL) scores were used to categorize patients into those with a clinically meaningful PTSD improvement (≥20 point decrease) or not (<20 point decrease or increase). PTSD and SUD were measured by ICD-9 codes. Propensity score weighting controlled for confounding in logistic and negative binomial models that estimated the association between clinically meaningful PTSD improvement and use of SUD treatment and number of SUD clinic visits. RESULTS: The 699 eligible patients were, on average, 40.4 (±13.2) years old, 66.2% white and 33.1% were married. After controlling for confounding, there was a 56% increased odds of any SUD treatment utilization among those with a PCL decrease ≥20 vs < 20 (OR = 1.56; 95%CI = 1.04-2.33) but there was no association with number of SUD treatment visits. CONCLUSIONS: Clinically meaningful reductions in PTSD symptoms were associated with any SUD treatment utilization but not amount of utilization. Improvement in PTSD symptoms, independent of the treatment modality, may enable SUD treatment seeking.

The association of opioid use duration and new depression episode among patients with and without insomnia.

OBJECTIVE: Insomnia commonly co-occurs with depression, chronic pain, and opioid use. Both insomnia and chronic opioid analgesic use (OAU) are independent risk factors for a new depression episode (NDE). This study determined if the association between longer OAU duration and NDE was stronger in those with versus without insomnia. DESIGN: Retrospective cohort. SETTING: Veterans Health Administration electronic medical records (2000-2012). PARTICIPANTS: New opioid users in follow-up (2002-2012), free of depression for two years prior to follow-up, and aged 18-80 (n = 70,997). METHODS: NDE was ≥ 2 ICD-9 codes in a 12-month period. Insomnia before OAU initiation was ≥1 ICD-9 code. Cox proportional hazard models stratified on insomnia assessed the relationship between initiating a 1-30, 31-90, or > 90 day period of OAU and NDE while controlling for confounders using inverse probability of treatment-weighted propensity scores (PS). RESULTS: Compared to 1-30 day OAU, 31-90 day was associated with NDE in those without (HR = 1.20; 95 percent CI: 1.12-1.28) but not with insomnia (HR = 1.06; 95 percent CI: 0.86-1.32). Results showed a stronger effect of chronic (>90) OAU in those with insomnia (HR = 1.59; 95 percent CI: 1.27-1.98) compared to those without (HR = 1.31; 95 percent CI: 1.21-1.42). However, all stratum-specific effects were not significantly different (p = 0.136). CONCLUSIONS: Although stratum-specific risks were statistically similar, there was evidence for a trend that chronic OAU is a stronger risk factor for NDE in those with versus without insomnia. Providers are encouraged to monitor sleep impairment among patients on opioid therapy, as sleep may be associated with greater risk for NDE in patients with chronic OAU.

The Prescription Opioids and Depression Pathways Cohort Study.

BACKGROUND: Results from studies using medical record data indicate chronic (>90 days) opioid analgesic use (OAU) is associated with new depressive episodes (NDE), worsening depression and risk for depression recurrence. This body of evidence is based on retrospective cohort studies and medical record data. Limitations of existing research are overcome in a new prospective cohort study of the opioid-depression relationship. METHODS: Prospective cohort of 1500 adult patients recruited from two health care systems. Eligible subjects started a new period of OAU and have 30 to 90 days of OAU at baseline. Diagnostic assessments for psychiatric disorders, structured measures of pain, pain functioning, opioid use, social support, sleep and impulsivity will be obtained at baseline, 6-month and 12-month follow-up. Baseline participants will be invited to 12 monthly brief assessments of pain-related functioning, depression symptoms and opioid use. INNOVATION: Robust control for confounding by indication and detailed phenotyping of depression and opioid use disorder. ANTICIPATED RESULTS: Chronic OAU will be associated with new onset of a depression phenotype characterized by anhedonia and somatic symptoms. This relationship will be partly, but not completely explained by impaired functioning and low social support. CONCLUSIONS: Although the annual number of opioid prescriptions in the United States has decreased, over 190 million patients have OAU each year. If chronic OAU leads to a clinically meaningful affective disorder, independent of pain, then we need to consider depression an important adverse effect of chronic OAU and adjust care for chronic pain accordingly.

PTSD improvement and incident cardiovascular disease in more than 1000 veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased risk for cardiovascular disease (CVD). Whether clinically meaningful PTSD improvement is associated with lowering CVD risk is unknown. METHODS: Eligible patients (n = 1079), were 30-70 years old, diagnosed with PTSD and used Veterans Health Affairs PTSD specialty clinics. Patients had a PTSD Checklist score (PCL) ≥ 50 between Fiscal Year (FY) 2008 and FY2012 and a second PCL score within 12 months and at least 8 weeks after the first PCL ≥ 50. Clinically meaningful PTSD improvement was defined by ≥20 point PCL decrease between the first and second PCL score. Patients were free of CVD diagnoses for 1 year prior to index. Index date was 12 months following the first PCL. Follow-up continued to FY2015. Cox proportional hazard models estimated the association between clinically meaningful PTSD improvement and incident CVD and incident ischemic heart disease (IHD). Sensitivity analysis stratified by age group (30-49 vs. 50-70 years) and depression. Confounding was controlled using propensity scores and inverse probability of exposure weighting. RESULTS: Patients were 48.9 ± 10.9 years of age on average, 83.3% male, 60.1% white, and 29.5% black. After controlling for confounding, patients with vs. without PTSD improvement did not differ in CVD risk (HR = 1.08; 95%CI: 0.72-1.63). Results did not change after stratifying by age group or depression status. Results were similar for incident IHD. CONCLUSIONS: Over a 2-7 year follow-up, we did not find an association between clinically meaningful PTSD improvement and incident CVD. Additional research is needed using longer follow-up.

Clinically meaningful posttraumatic stress disorder (PTSD) improvement and incident hypertension, hyperlipidemia, and weight loss.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with increased risk for cardiometabolic disease. Clinically meaningful PTSD improvement is associated with a lower risk for diabetes, but it is not known if similar associations exist for incident hypertension, hyperlipidemia, and clinically relevant weight loss (i.e., ≥5% loss). METHOD: Medical record data from Veterans Health Affairs patients with clinic encounters between fiscal year (FY) 2008 to 2015 were used to identify patients with worsening or no PTSD improvement (i.e., PTSD checklist (PCL) score decrease <10), small (10-19 point PCL decrease), and large (≥20 point PCL decrease) PTSD improvement. To estimate the association between degree of PTSD improvement and incident hypertension (n = 979), incident hyperlipidemia (n = 1,139) and incident ≥5% weight loss (1,330), we computed Cox proportional hazard models, controlling for confounding using inverse probability of exposure weighting (IPEW). RESULTS: Overall, patients were about 40 years of age, 80% male and 65% White. Worsening or no PCL change occurred in about 60%, small improvement in 20%, and large improvement in 20%. After weighting data, compared with worsening or no change, both small and large PTSD improvements were associated, albeit not significantly, with lower risks for hypertension (HR = 0.68; 95% confidence interval, CI [0.46, 1.01] and HR = 0.79; 95% CI [0.53, 1.18], respectively). In weighted data, PTSD improvement was not associated with incident hyperlipidemia or ≥5% weight loss. CONCLUSIONS: We observed limited evidence for an association between PTSD improvement and decreased hypertension risk. PCL decreases were not associated with hyperlipidemia or ≥5% weight loss. Further studies that measure potential physical health benefits of change in specific PTSD symptoms are needed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Large posttraumatic stress disorder improvement and antidepressant medication adherence.

BACKGROUND: Patients with vs. without posttraumatic stress disorder (PTSD) are more likely to have poor antidepressant medication (ADM) adherence but it is unclear if improved PTSD is associated with ADM adherence. We determined if clinically meaningful PTSD symptom reduction was associated with ADM adherence. METHODS: Electronic health record data (2008-2015) was obtained from 742 Veterans Health Affairs (VHA) patients using PTSD specialty clinics with a PTSD diagnosis and PTSD checklist (PCL) score ≥50. The last PCL in the exposure year after the first PCL≥50 was used to identify patients with a clinically meaningful PCL decrease (≥20 point) versus those without (< 20 point). Patients had a depression diagnosis in the 12-months before the exposure year and received an ADM in the exposure year. Proportion of days covered ≥80% in exposure year defined adherence. Confounding was controlled using propensity scores and inverse probability of treatment weighting. RESULTS: Patients were 42.2 ±â€¯13.1 years of age, 63.9% white and 18.9% had a clinically meaningful PCL decrease. After controlling for confounding variables, patients with vs. without a clinically meaningful PCL decrease were significantly more likely to be adherent (OR = 1.78; 95% CI:1.16-2.73). However, adherence remained low in both patients with and without meaningful PCL decrease (53.5% vs. 39.3%). LIMITATIONS: The sample was limited to VHA patients. Patients may not have taken medication as prescribed. CONCLUSIONS: Large reductions in PTSD symptoms are associated with ADM adherence. Prior literature suggests ADM adherence improves depression symptoms. Thus, PTSD symptom reduction may lead to better depression outcomes.

Combined effect of posttraumatic stress disorder and prescription opioid use on risk of cardiovascular disease.

AIM: Prescription opioid analgesic use (OAU) is associated with increased risk of cardiovascular disease (CVD). OAU is more common in patients with than without posttraumatic stress disorder (PTSD), and PTSD is associated with higher CVD risk. We determined whether PTSD and OAU have an additive or multiplicative association with incident CVD. METHODS AND RESULTS: Veterans Health Affairs patient medical record data from 2008 to 2015 was used to identify 2861 patients 30-70 years of age, free of cancer, CVD and OAU for 12 months before index date. We defined a four-level exposure variable: 1) no PTSD/no OAU, 2) OAU alone, 3) PTSD alone and 4) PTSD+OAU. Cox proportional hazard models estimated the association between the exposure variable and incident CVD. The mean age was 49.0 (±11.0), 85.7% were male and 58.3% were White, 34.4% had no PTSD/no OAU, 32.9% had PTSD alone, 10.6% had OAU alone, and 22.1% had PTSD+OAU. Compared with patients with no PTSD/no OAU, those with PTSD alone were not at increased risk of incident CVD (hazard ratio = 0.82; 95% confidence interval (CI): 0.63-1.17); however, OAU alone and PTSD+OAU were both significantly associated with incident CVD (hazard ratio = 1.99; 95% CI:1.36-2.92 and hazard ratio = 2.20; 95% CI: 1.61-3.02). There was no significant additive or multiplicative PTSD and OAU association with incident CVD. CONCLUSION: OAU is associated with nearly a two-fold increased risk of CVD in patients with and without PTSD. Despite no additive or multiplicative interaction effects, the high prevalence of OAU in PTSD may represent a novel contributor to the elevated CVD burden among patients with PTSD.

PTSD symptom decrease and use of weight loss programs.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with poor health behaviors, including low utilization of Veteran Health Affairs (VHA) weight loss programs. It is not known if clinically meaningful PTSD improvement is associated with increased use of weight loss programs. METHODS: Medical record data was obtained from VHA patients who received PTSD specialty care between Fiscal Year (FY) 2008 to FY2012. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease between the first PCL ≥ 50 and a second PCL at least 8 weeks later and within 12 months of the first PCL. Eligible patients, n = 993, were followed through FY2015. Propensity scores and inverse probability of exposure weighting controlled confounding. Cox proportional hazard models estimated the association between clinically meaningful PCL decrease and weight loss clinic utilization. Supplemental analysis compared both PTSD groups vs. no PTSD. RESULTS: Patients were 44.8 (SD ±14) years of age, 88.9% male and 66.8% white. Patients with vs. without a clinically meaningful PCL decrease were more likely to use a weight loss clinic (HR = 1.37; 95%CI:1.02-1.85). Among those with a weight loss encounter, PCL decrease was not associated with the number of encounters (RR = 1.13; 95%CI:0.70-1.81). Compared to no PTSD, patients with PTSD improvement had more weight loss encounters. CONCLUSIONS: Large improvements in PTSD are associated with increased utilization of weight loss programs, and PTSD is not a barrier to seeking weight loss counseling. Research to understand why improvement in PTSD is not related to better weight loss outcomes is needed.