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.

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.

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.

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).

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.

Association Between Clinically Meaningful Posttraumatic Stress Disorder Improvement and Risk of Type 2 Diabetes.

Importance: Posttraumatic stress disorder (PTSD) is associated with increased risk of type 2 diabetes (T2D). Improvement in PTSD has been associated with improved self-reported physical health and hypertension; however, there is no literature, to our knowledge, on whether PTSD improvement is associated with T2D risk. Objective: To examine whether clinically meaningful PTSD symptom reduction is associated with lower risk of T2D. Design, Setting, and Participants: This retrospective cohort study examined Veterans Health Affairs medical record data from 5916 patients who received PTSD specialty care between fiscal years 2008 and 2012 and were followed up through fiscal year 2015. Eligible patients had 1 or more PTSD Checklist (PCL) scores of 50 or higher between fiscal years 2008 and 2012 and a second PCL score within the following 12 months and at least 8 weeks after the first PCL score of 50 or higher. The index date was 12 months after the first PCL score. Patients were free of T2D diagnosis or an antidiabetic medication use for 12 months before the index date and had at least 1 visit after the index date. Data analyses were completed during January 2019. Exposures: Reduction in PCL scores during a 12-month period was used to define patients as those with a clinically meaningful improvement (≥20-point PCL score decrease) and patients with less or no improvement (<20-point PCL score decrease). Main Outcomes and Measures: Incident T2D diagnosed during a 2- to 6-year follow-up. Results: Medical records from a total of 1598 patients (mean [SD] age, 42.1 [13.4] years; 1347 [84.3%] male; 1060 [66.3%] white) were studied. The age-adjusted cumulative incidence of T2D was 2.6% among patients with a clinically meaningful PCL score decrease and 5.9% among patients without a clinically meaningful PCL score decrease (P = .003). After control for confounding, patients with a clinically meaningful PCL score decrease were significantly less likely to develop T2DM compared with those without a clinically meaningful decrease (hazard ratio, 0.51; 95% CI, 0.26-0.98). Conclusions and Relevance: The findings suggest that clinically meaningful reductions in PTSD symptoms are associated with a lower risk of T2D. A decrease in PCL score, whether through treatment or spontaneous improvement, may help mitigate the greater risk of T2D in patients with PTSD.

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.

Factors Associated With Receipt of Cognitive-Behavioral Therapy or Prolonged Exposure Therapy Among Individuals With PTSD.

OBJECTIVE: The aim of this study was to systematically review variables associated with initiation of trauma-centered cognitive-behavioral therapy (TC-CBT) among individuals with posttraumatic stress disorder (PTSD). METHODS: PubMed, PsycINFO, Web of Science, Published International Literature on Traumatic Stress (PILOTS), and Scopus were searched in a systematic manner up to 2018, and 26 relevant studies were recovered and analyzed. RESULTS: The average weighted initiation rate was 6% in larger hospital systems with a high rate of trauma and 28% in outpatient mental health settings (range 4%-83%). Older age (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.51-1.61), female gender (OR=1.18, 95% CI=1.08-1.27), black or other racial-ethnic minority group (OR=1.16, 95% CI=1.03-1.28), Veterans Affairs PTSD service connection status (OR=2.30, 95% CI=2.18-2.42), mental health referral (OR=2.28, 95% CI=1.05-3.50), greater staff exposure to TC-CBT (OR=2.30, 95% CI=2.09-2.52), adaptability of TC-CBT to staff workflow (OR=4.66, 95% CI=1.60-7.72), greater PTSD severity (OR=1.46, 95% CI=1.13-1.78), and comorbid depression (OR=1.21, 95% CI=1.14-1.29) increased the likelihood of TC-CBT initiation, whereas delayed treatment reduced the likelihood of TC-CBT initiation (OR=0.93, 95% CI=0.92-0.95). Qualitative studies showed that mental health beliefs (stigma and lack of readiness), provider organizational factors (low availability, privacy issues), and patient lack of time (logistics) were perceived as barriers to initiation by patients and providers. CONCLUSIONS: TC-CBT initiation increased among patients who were older and female. Initiation was also higher among providers who had more exposure to TC-CBT in their work environment and when TC-CBT fit into their existing workflow.

Comorbid Conditions Explain the Association Between Posttraumatic Stress Disorder and Incident Cardiovascular Disease.

Background Posttraumatic stress disorder ( PTSD ) is associated with risk of cardiovascular disease ( CVD ). Biopsychosocial factors associated with PTSD likely account for some or all of this association. We determined whether 1, or a combination of comorbid conditions explained the association between PTSD and incident CVD . Methods and Results Eligible patients used 1 of 5 Veterans Health Affairs medical centers distributed across the United States. Data were obtained from electronic health records. At index date, 2519 Veterans Health Affairs ( VA ) patients, 30 to 70 years of age, had PTSD diagnoses and 1659 did not. Patients had no CVD diagnoses for 12 months before index date. Patients could enter the cohort between 2008 and 2012 with follow-up until 2015. Age-adjusted Cox proportional hazard models were computed before and after adjusting for comorbidities. Patients were middle aged (mean=50.1 years, SD ±11.0), mostly male (87.0%), and 60% were white. The age-adjusted association between PTSD and incident CVD was significant (hazard ratio=1.41; 95% CI : 1.21-1.63). After adjustment for metabolic conditions, the association between PTSD and incident CVD was attenuated but remained significant (hazard ratio=1.23; 95% CI : 1.06-1.44). After additional adjustment for smoking, sleep disorder, substance use disorder, anxiety disorders, and depression, PTSD was not associated with incident CVD (hazard ratio=0.96; 95% CI : 0.81-1.15). Conclusions PTSD is not an independent risk factor for CVD . Physical and psychiatric conditions and smoking that co-occur with PTSD explain why this patient population has an increased risk of CVD . Careful monitoring may limit exposure to CVD risk factors and subsequent incident CVD .

The influence of anxiety sensitivity on opioid use disorder treatment outcomes.

Given the high rates of relapse among patients with opioid use disorder (OUD), it is crucial to identify modifiable risk factors for negative treatment outcomes. Anxiety sensitivity (AS) is 1 such risk factor that may be associated with negative OUD treatment outcomes. The present study examined the potential impact of AS on the withdrawal process, subsequent treatment engagement, and relapse among individuals with OUD. Adults undergoing inpatient detoxification (N = 90) completed self-report and researcher-administered questionnaires on Day 4 of a 5-day buprenorphine-assisted detoxification protocol, and 1 month later a follow-up evaluation assessed treatment engagement and relapse. Although 68% of the sample engaged in subsequent treatment, 76% demonstrated poor adherence. Over half the sample (57%) reported opioid relapse 1 month later. Results revealed that greater AS and younger age predicted greater fear of withdrawal during detoxification. Contrary to the research hypotheses, AS was not a significant predictor of other treatment outcomes; rather, fear of withdrawal and prior number of opioid detoxifications predicted greater subjective withdrawal severity. During detoxification, younger age was related to greater cravings, and being a male was associated with a higher likelihood of receiving prescription anxiolytics. Following detoxification treatment, referral to residential treatment predicted greater treatment engagement, whereas greater opioid craving, number of days in an uncontrolled environment, and any nonopioid substance use postdischarge predicted greater opioid relapse. Failure to find a relationship between AS and the withdrawal process is potentially a function of the buprenorphine protocol. Overall, findings may have important implications for the treatment of OUD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).