Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.

BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine. METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38). RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study. DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.

Problematic Alcohol Use Trajectories in U.S. Military Veterans during a Public Health Crisis: Results from a 3-year, Nationally Representative, Longitudinal Study.

A growing number of studies have examined alcohol use during the COVID-19 pandemic. However, few longitudinal studies evaluated the prevalence and correlates of different trajectories of problematic alcohol use in vulnerable segments of the population, such as US veterans, over the 3-year course of the COVID-19 pandemic. Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative, longitudinal study of 2,441 US veterans. Latent growth mixture modeling was used to identify the trajectories and correlates of problematic alcohol use. Four trajectories were identified: consistent (N = 170, weighted 7.2%), decreasing (N = 38, weighted 2.2%), increasing (N = 22, weighted 1.2%), and low (N = 2,211, weighted 89.4%) problematic alcohol use. Greater household income, pre-pandemic drug use disorder (DUD), lower social support, and COVID-19 infection to self or non-household members were associated with an increasing relative to decreasing problematic alcohol use trajectory. Greater household income, adverse childhood experiences (ACEs), pre-pandemic DUD, lower social support, and greater COVID-related social restriction stress were associated with an increasing relative to a low problematic alcohol use trajectory. Younger age, male sex, ACEs, pre-pandemic DUD, lower pre-pandemic and greater decline in protective psychosocial characteristics, COVID-19 infection to non-household member, and lower COVID-related financial stress were associated with a consistent relative to a low problematic alcohol use trajectory. Overall, pre-pandemic greater income, DUD, and lower social support were associated with an increase in problematic alcohol use among US veterans during the COVID-19 pandemic. Results may help inform prevention efforts to mitigate problematic alcohol use during prolonged crises in this population.

Positive personality traits moderate persistent high alcohol consumption, determined by polygenic risk in U.S. military veterans: results from a 10-year, population-based, observational cohort study.

BACKGROUND: Understanding the interplay between psychosocial factors and polygenic risk scores (PRS) may help elucidate the biopsychosocial etiology of high alcohol consumption (HAC). This study examined the psychosocial moderators of HAC, determined by polygenic risk in a 10-year longitudinal study of US military veterans. We hypothesized that positive psychosocial traits (e.g. social support, personality traits, optimism, gratitude) may buffer risk of HAC in veterans with greater polygenic liability for alcohol consumption (AC). METHODS: Data were analyzed from 1323 European-American US veterans who participated in the National Health and Resilience in Veterans Study, a 10-year, nationally representative longitudinal study of US military veterans. PRS reflecting genome-wide risk for AC (AUDIT-C) was derived from a Million Veteran Program genome-wide association study (N = 200 680). RESULTS: Among the total sample, 328 (weighted 24.8%) had persistent HAC, 131 (weighted 9.9%) had new-onset HAC, 44 (weighted 3.3%) had remitted HAC, and 820 (weighted 62.0%) had no/low AC over the 10-year study period. AUDIT-C PRS was positively associated with persistent HAC relative to no/low AC [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI) = 1.23-1.67] and remitted HAC (RRR = 1.63, 95% CI = 1.07-2.50). Among veterans with higher AUDIT-C PRS, greater baseline levels of agreeableness and greater dispositional gratitude were inversely associated with persistent HAC. CONCLUSIONS: AUDIT-C PRS was prospectively associated with persistent HAC over a 10-year period, and agreeableness and dispositional gratitude moderated this association. Clinical interventions designed to target these modifiable psychological traits may help mitigate risk of persistent HAC in veterans with greater polygenic liability for persistent HAC.

Analysis of Drugs in Saliva of US Military Veterans Treated for Substance Use Disorders Using Supported Liquid Extraction and Surface-Enhanced Raman Spectral Analysis.

According to the Center for Disease Control, there were more than 107,000 US drug overdose deaths in 2021, over 80,000 of which due to opioids. One of the more vulnerable populations is US military veterans. Nearly 250,000 military veterans suffer from substance-related disorders (SRD). For those seeking treatment, buprenorphine is prescribed to help treat opioid use disorder (OUD). Urinalysis is currently used to monitor buprenorphine adherence as well as to detect illicit drug use during treatment. Sometimes sample tampering occurs if patients seek to generate a false positive buprenorphine urine test or mask illicit drugs, both of which can compromise treatment. To address this problem, we have been developing a point-of-care (POC) analyzer that can rapidly measure both medications used for treatment and illicit drugs in patient saliva, ideally in the physi-cian's office. The two-step analyzer employs (1) supported liquid extraction (SLE) to isolate the drugs from the saliva and (2) surface-enhanced Raman spectroscopy (SERS) to detect the drugs. A prototype SLE-SERS-POC analyzer was used to quantify buprenorphine at ng/mL concentrations and identify illicit drugs in less than 1 mL of saliva collected from 20 SRD veterans in less than 20 min. It correctly detected buprenorphine in 19 of 20 samples (18 true positives, 1 true negative and 1 false negative). It also identified 10 other drugs in patient samples: acetaminophen, amphetamine, cannabidiol, cocaethylene, codeine, ibuprofen, methamphetamine, methadone, nicotine, and norbuprenorphine. The prototype analyzer shows evidence of accuracy in measuring treatment medications and relapse to drug use. Further study and development of the system is warranted.

Alcohol Craving and Psychiatric Disorders Among Current Drinkers.

BACKGROUND AND OBJECTIVES: Previous research has shown that alcohol craving is associated with psychiatric comorbidities. However, no population studies have examined the odds of psychiatric disorders in cravers and noncravers. The purpose of this study was to investigate current prevalence rates and odds ratios of psychiatric disorders among alcohol drinkers with and without alcohol craving in a population-based sample. We also compared four craving groups (cravers with and without alcohol use disorder [AUD], noncravers with and without AUD) for psychiatric comorbidities. METHODS: The study data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). A subset of the NESARC sample (N = 22 000) who reported alcohol use during the past 12 months was included. Prevalence rates of psychiatric disorders were compared among current drinkers with alcohol craving (N = 900) and without alcohol craving (N = 21 500). RESULTS: Cravers had higher prevalence rates of current psychiatric disorders than noncravers. Even after adjustment for other psychiatric disorders including AUD, cravers had significantly higher odds of any substance use disorder (adjusted odds ratio [AOR], 9.01), any mood disorder (AOR, 1.78), any anxiety disorder (AOR, 1.86), and any personality disorder (AOR, 1.92) than noncravers. Interestingly, cravers without AUD had even higher rates of any anxiety disorder and any personality disorder than noncravers with AUD. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Alcohol craving is associated with a higher prevalence of various psychiatric disorders. These findings suggest that alcohol craving may be related to transdiagnostic features that are present across various psychiatric disorders. (Am J Addict 2021;30:34-42).

Sex Differences in Opioid Use Disorder Prevalence and Multimorbidity Nationally in the Veterans Health Administration.

OBJECTIVE: Opioid use disorder (OUD) is a significant problem among US veterans with increasing rates of OUD and overdose, and thus has substantial importance for service delivery within the Veterans Health Administration (VHA). Among individuals with OUD, several sex- specific differences have begun to emerge regarding co-occurring medical, psychiatric and pain-related diagnoses. The rates of such multimorbidities are likely to vary between men and women with OUD and may have important implications for treatment within the VHA but have not yet been studied. Methods: The present study utilized a data set that included all veterans receiving VHA health care during Fiscal Year (FY) 2012 (October 1, 2011 through September 30, 2012), who were diagnosed during the year with opioid dependence or abuse. VHA patients diagnosed with OUD nationwide in FY 2012 were compared by sex on proportions with OUD, and among those with OUD, on sociodemographic characteristics, medical, psychiatric and pain-related diagnoses, as well as on service use, and psychotropic and opioid agonist prescription fills. Results: During FY 2012, 48,408 veterans were diagnosed with OUD, 5.77% of whom were women. Among those veterans with OUD, few sociodemographic differences were observed between sexes. Female veterans had a higher rate of psychiatric diagnoses, notably mood, anxiety and personality disorders, as well as higher rates of pain-related diagnoses, such as headaches and fibromyalgia, while male veterans were more likely to have concurrent, severe medical co-morbidities, including hepatic disease, HIV, cancers, peripheral vascular disease, diabetes and related complications, and renal disease. There were few differences in health service utilization, with women reporting greater receipt of prescriptions for anxiolytic/sedative/hypnotics, stimulants and lithium. Men and women did not differ in receipt of opioid agonist medications or mental health/substance use treatments. Conclusions: There are substantial sex-specific differences in patterns of multimorbidity among veterans with OUD, spanning medical, psychiatric and pain-related diagnoses. These results illustrate the need to view OUD as a multimorbid condition and design interventions to target such multimorbidities. The present study highlights the potential benefits of sex-specific treatment and prevention efforts among female veterans with OUD and related co-occurring disorders.

Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE: Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS: For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS: Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS: In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.

Alcohol Abstainer Status and Prazosin Treatment in Association with Changes in Posttraumatic Stress Disorder Symptoms in Veterans with Comorbid Alcohol Use Disorder and Posttraumatic Stress Disorder.

BACKGROUND: The noradrenergic system has been implicated in alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD), with adrenergic agents reducing drinking in individuals with AUD and improving sleep disturbances in individuals with PTSD. In a recent clinical trial, prazosin, an α1-adrenergic antagonist, was not superior to placebo in reducing PTSD symptoms, sleep problems, or alcohol consumption in a comorbid population; however, patients in both treatment conditions improved in all symptom domains over the course of treatment. It remains unknown whether alcohol abstinence is related to changes in PTSD symptoms and medication effects in individuals with this comorbidity. METHODS: Veterans with comorbid alcohol dependence and PTSD (n = 96) were randomized to prazosin (16 mg) or placebo in a 12-week outpatient, double-blind clinical trial. In this secondary data analysis, we examined main effects of alcohol abstainer status (abstainer vs. nonabstainer), treatment, and their interaction on changes in PTSD symptoms over time using linear mixed models. RESULTS: There was a main effect of alcohol abstainer status on symptoms of PTSD (p = 0.03), such that nonabstainers had lower total Clinician-Administered PTSD Scale (CAPS) scores than abstainers. There was a significant treatment by alcohol abstainer status interaction (p = 0.01); specifically, among placebo-treated individuals, those who did not abstain from alcohol had lower total CAPS scores compared to alcohol abstainers. Within the prazosin-treated group, abstainers and nonabstainers did not differ on total CAPS scores. Results were similar for the avoidance (p = 0.02), reexperiencing (p = 0.01), and hyperarousal (p = 0.04) subscales, such that placebo-treated nonabstainers had lower CAPS scores overall. CONCLUSIONS: Overall, prazosin treatment was not significantly related to changes in PTSD symptoms over the course of the 12-week clinical trial in a comorbid population. Interestingly, placebo-treated alcohol nonabstainers had a significant reduction in PTSD symptoms. Whether placebo-treated individuals continued to use alcohol because of ongoing symptoms of PTSD is not known.

Suicidal ideation in military veterans with alcohol dependence and PTSD: The role of hostility.

BACKGROUND AND OBJECTIVES: Suicide is a significant public health problem among US military Veterans with rates exceeding civilian samples. Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) are both associated with increases in suicidality. Given that risk of suicide is higher among those with both disorders, the study of relevant risk factors among those in this group is important. The current investigation focused on one such factor, hostility, and examined both overt hostility (ie, hostility that is more behavioral in nature and directed outwardly) and covert hostility (ie, hostility that is cognitive in nature and introspective) and their relationships to suicidal ideation. METHODS: Ninety-three Veterans participating in a randomized, double-blind, placebo-controlled treatment study evaluating the efficacy of the alpha-adrenergic agonist prazosin completed measures assessing overt hostility, covert hostility, and suicidal ideation at baseline. Depression symptoms and PTSD symptom severity also were assessed. RESULTS: Of the total sample, 60 participants (63.8%) indicated that they experienced suicidal ideation at some point in their lives. Covert hostility, in addition to PTSD symptom severity were found to be associated with the presence of lifetime suicidal ideation. Furthermore, depression symptoms were found to be associated with greater intensity of that ideation. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Findings highlight the importance of covert hostility as it relates to suicidal ideation among those with comorbid PTSD and AD and provides information which may help inform treatment approaches for high-risk military Veterans. (Am J Addict 2018;27:124-130).

Partnering with Psychiatry to Close the Education Gap: An Approach to the Addiction Epidemic.

Addiction has reached epidemic proportions in the U.S., yet the workforce prepared to care for this population is woefully inadequate. Of the 23 million Americans suffering from addiction, only 11% receive treatment, creating a substantial treatment gap. There have been calls to improve addiction education at all levels of training in order to prepare medical providers with the skills to identify patients with substance use, briefly treat if indicated, and/or refer more complex cases to specialty care. These calls have been put forth to address the education gap, wherein physicians in training are exposed to numerous patients who are suffering from addiction but have few curricular hours dedicated to the identification and management of this population. We propose that strategic partnerships between psychiatry and internal medicine can address the education gap that exists with regard to addiction, ultimately addressing the treatment gap which is plaguing this country.

Posttraumatic Stress Disorder and Alcohol Use Disorder: A Critical Review of Pharmacologic Treatments.

Treatment of alcohol use disorder (AUD) is complicated by the presence of psychiatric comorbidity including posttraumatic stress disorder (PTSD). This is a critical review of the literature to date on pharmacotherapy treatments of AUD and PTSD. A systematic literature search using PubMed MESH terms for alcohol and substance use disorders, PTSD, and treatment was undertaken to identify relevant randomized controlled trials (RCTs). The studies were independently evaluated (ILP and TLS) and those that evaluated the efficacy of a pharmacotherapy for individuals diagnosed with AUD and PTSD and were RCTs were selected. Studies were grouped in 3 categories: (i) those that evaluated first-line treatments for PTSD, (ii) those that evaluated medications to target AUD, and (iii) those that evaluated medications hypothesized to be effective in targeting alcohol consumption as well as PTSD symptoms. Nine RCTs were identified; 3 focused on medications to treat PTSD, 4 focused on AUD, and 3 to target both. One study included both a medication to treat PTSD and 1 to treat AUD so was discussed twice. All but 1 of the studies found that PTSD symptoms and drinking outcomes improved significantly over time. There is not 1 agent with clear evidence of efficacy in this comorbid group. The results for medications to treat PTSD are inconclusive because of contradictory results. There was weak evidence to support the use of medications to treat AUD among those with comorbidity with PTSD. Findings for medications that were hypothesized to treat both disorders were also contradictory. Most studies provided a combination of interventions to treat both disorders. Despite the contradictory results, this review suggests that individuals with AUD and comorbid PTSD can safely be prescribed medications used in noncomorbid populations and patients improve with treatment.

No Wrong Doors: Findings from a Critical Review of Behavioral Randomized Clinical Trials for Individuals with Co-Occurring Alcohol/Drug Problems and Posttraumatic Stress Disorder.

Prior reviews of behavioral treatments for individuals with comorbid alcohol and drug use disorders (substance use disorder SUD) and posttraumatic stress disorder (PTSD) have not systematically considered whether comparison conditions are matched to target treatments on time and attention. A systematic literature search using PubMed MESH terms for alcohol and substance use disorders, PTSD, and treatment identified relevant behavioral randomized clinical trials (RCTs) that evaluated PTSD-oriented exposure-based treatments, addiction-focused treatments, and coping-based treatments that do not involve exposure to trauma memories. Information pertaining to within-subject changes over time and between-subject differences, quality of control condition, recruitment efficiency, and assessment and treatment retention was synthesized. Alcohol and drug outcomes were described separately when possible. Twenty-four behavioral RCTs were identified: 7 exposure based, 6 addiction focused, and 11 coping based. Seven studies included SUD intervention comparison conditions matched to the target intervention on time and attention. Most of the 24 studies found that participants in both the experimental and control conditions improved significantly over time on SUD and PTSD outcomes. No study found significant between-group differences in both SUD and PTSD outcomes favoring the experimental treatment. Despite greater treatment dropout, there was greater improvement in some PTSD outcomes for exposure-based interventions than the control conditions, including when the control conditions were matched for time and attention. Addiction-focused and coping-based interventions did not generally show an advantage over comparably robust controls, although some coping-based interventions yielded better drug use outcomes than control conditions. When available, interventions that integrate exposure-based PTSD treatment and behavioral SUD treatment are recommended as they are associated with better PTSD outcomes than SUD care matched for time and attention. However, the results of this critical review also suggest that people with SUD/PTSD can benefit from a variety of treatment options, including standard SUD care.

GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose-Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers.

BACKGROUND: The heritable risk for alcohol use disorder (AUD) is expressed partly through alterations in subjective alcohol response. In this study, we investigated the effects of 2 AUD-risk-associated single nucleotide polymorphisms, GABRA2 rs279858 and GRIK1 rs2832407, on the subjective response to alcohol administered intravenously to healthy social drinkers in a laboratory setting. METHODS: In total, 93 self-identified European American social drinkers underwent 3 blinded laboratory sessions in which they received intravenous infusions of ethanol at 3 target blood alcohol levels (0.00 mg%, 40 mg%, and 100 mg%) using a "clamp" procedure. The self-reported Biphasic Alcohol Effects Scale (BAES) stimulation and sedation subscales were the primary outcome measures. We examined the effects of these 2 genetic variants on subjective response to alcohol. RESULTS: For the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the GABRA2 rs279858 C "risk" allele for AUD exhibited the greatest stimulant responses to high-dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p = 0.001, post hoc contrast for C-allele, p = 0.012). For the BAES sedation subscale scores, adjusting for the same covariates, we detected a dose-by-allele count interaction effect (p = 0.0044) such that subjects with 2 copies of the GRIK1 C "risk" allele reported the greatest sedative response to the higher alcohol dose. CONCLUSIONS: This study suggests that gene variants contributing to the risk for AUD may alter features of the alcohol dose-response relationship in specific ways. GABRA2 rs279858*C enhances stimulant responses to higher levels of alcohol, while the GRIK1 rs2832407*C-allele increases sedative responses. In summary, GRIK1 and GABRA2 variants have distinct effects on the dose-related subjective response to intravenous alcohol in humans.

Effect of Intravenous Ethanol on Capsaicin-Induced Hyperalgesia in Human Subjects.

BACKGROUND: The objective of this study was to assess ethanol's (EtOH's) effects on capsaicin-induced hyperalgesia in healthy participants. Specifically, we investigated the change in area of capsaicin-induced hyperalgesia following 3 interventions: intravenous EtOH at 2 targeted breath alcohol concentrations (BrAC), or placebo. METHODS: Eighteen participants participated in 3 test days in a randomized order. Each test day, participants received an intradermal capsaicin injection on the volar surface of the forearm, followed by either infusion of high concentration EtOH (targeted BrAC = 0.100 g/dl), low concentration EtOH (targeted BrAC = 0.040 g/dl), or placebo. The area of hyperalgesia was determined by von Frey technique at 2 time points, prior to EtOH infusion, and again when target BrAC was reached. The primary outcome was the percent change in the area of capsaicin-induced hyperalgesia. Additional outcome measures included the visual analogue scale of mood states (VAS), which was administered at each time point. RESULTS: There was a marked 30% reduction in the area of capsaicin-induced hyperalgesia with infusion of a high concentration of EtOH (p < 0.05). Low concentration EtOH produced a 10% reduction in hyperalgesia area, although this finding did not reach significance. Further, participants reported significant feelings of euphoria and drowsiness at high concentrations of EtOH (p < 0.05), as measured by the VAS. CONCLUSIONS: In a human model examining pain phenomena related to central sensitization, this study is the first to demonstrate that capsaicin-induced hyperalgesia is markedly attenuated by EtOH. The capsaicin experimental pain paradigm employed provides a novel approach to evaluate EtOH's effects on pain processing. The antihyperalgesic effects of EtOH observed have important clinical implications for the converging fields of substance abuse and pain medicine and may inform why patients with chronic pain often report alcohol use as a form of self-medication.

Prazosin for Veterans with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence: A Clinical Trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) is an important and timely clinical issue particularly for combat veterans. Few pharmacologic options are available to treat PTSD, particularly among military personnel, and they are not based on rational neurobiology. The evidence for noradrenergic dysregulation in PTSD is strong, and the alpha-adrenergic agonist prazosin is one of the most promising medications to treat sleep disturbances associated with PTSD as well as PTSD symptoms among both veterans and civilians. Evidence also implicates noradrenergic dysregulation in the pathophysiology of alcohol dependence (AD); prazosin also may have efficacy in treating this disorder. The use of prazosin represents a rational and compelling approach for the treatment of PTSD and comorbid AD. Given the high rates of comorbid AD in trauma survivors with PTSD, and the enormous impact that these comorbid disorders have on psychosocial function and well-being, finding effective treatments for this population is of high clinical importance. METHODS: Ninety-six veterans with PTSD and comorbid AD were randomized to receive prazosin (16 mg) or placebo in an outpatient, randomized, double-blind, clinical trial for 13 weeks. Main outcomes included symptoms of PTSD, sleep disturbances, and alcohol use. RESULTS: Symptoms of PTSD improved over time, but contrary to the hypothesis, there was no medication effect on PTSD symptoms, or on sleep. Alcohol consumption also decreased over time, but there were no significant differences in outcomes between medication groups. CONCLUSIONS: Prazosin was not effective in treating PTSD symptoms, improving sleep, or reducing alcohol consumption overall in this dually diagnosed group. This does not support the use of prazosin in an actively drinking population and suggests that the presence of a comorbid condition affects the efficacy of this medication. This study highlights the importance of conducting clinical trials in "real-world" patients, as results may vary based on comorbid conditions.

Correlates of major depressive disorder with and without comorbid alcohol use disorder nationally in the veterans health administration.

BACKGROUND AND OBJECTIVES: This study assesses medical and psychiatric comorbidities, service utilization, and psychotropic medication prescriptions in veterans with comorbid major depressive disorder (MDD) and alcohol use disorder (AUD) relative to veterans with MDD alone. METHODS: Using cross-sectional administrative data (fiscal year [FY]2012: October 1, 2011-September 30, 2012) from the Veterans Health Administration (VHA), we identified veterans with a diagnosis of current (12-month) MDD nationally (N = 309,374), 18.8% of whom were also diagnosed with current (12-month) AUD. Veterans with both MDD and AUD were compared to those with MDD alone on sociodemographic characteristics, current (12-month) medical and psychiatric disorders, service utilization, and psychotropic prescriptions. We then used logistic regression analyses to calculate odds ratio and 95% confidence interval of characteristics that were independently different between the groups. RESULTS: Dually diagnosed veterans with MDD and AUD, relative to veterans with MDD alone, had a greater number of comorbid health conditions, such as liver disease, drug use disorders, and bipolar disorder as well as greater likelihood of homelessness and higher service utilization. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Dually diagnosed veterans with MDD and AUD had more frequent medical and psychiatric comorbidities and more frequently had been homeless. These data suggest the importance of assessing the presence of comorbid medical/psychiatric disorders and potential homelessness in order to provide appropriately comprehensive treatment to dually diagnosed veterans with MDD and AUD and indicate a need to develop more effective treatments for combined disorders.

Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.

BACKGROUND: The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials. METHODS: Subjects (n = 18) were administered, 1 week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80, and 120 mg/dl, respectively. Urinary EtG/EtS was measured at timed intervals during a 24-hour hospitalization and twice daily thereafter. In addition, participants from 2 clinical trials provided samples for EtG/EtS and drinking histories. Cutoffs for EtG/EtS of 100/50, 200/100, and 500/250 ng/ml were evaluated. RESULTS: Twelve hours following each challenge, EtG was always positive at the 100 and 200 cutoffs, but at 24 hours sensitivity was poor at all cutoffs following the low dose, and poor after 48 hours regardless of dose or cutoff. Similarly, in the clinical trials EtG sensitivity was good for detecting any drinking during the last 24 hours at the 2 lowest cutoffs, but under 40% during the last 24 to 48 hours. Sensitivity was reduced at the 500 ng/ml cutoff. Discrepancies between EtG and EtS were few. Comparison of self-reports of abstinence and EtG-confirmed abstinence indicated underreporting of drinking. CONCLUSIONS: Any drinking the night before should be detectable the following morning with EtG cutoffs of 100 or 200 ng/ml. Twenty-four hours after drinking, sensitivity is poor for light drinking, but good for heavier consumption. At 48 hours, sensitivity is low following 6 drinks or less. Increasing the cutoff to 500 ng/ml leads to substantially reduced sensitivity. Monitoring both EtG and EtS should usually be unnecessary. We recommend EtG-confirmed self-reports of abstinence for evaluation of outcomes in clinical trials.

Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans.

BACKGROUND: Disulfiram and naltrexone were evaluated in treatment of individuals with co-occurring alcohol dependence and other Axis I disorders (e.g., Major Depression). We explored pharmacogenetic interactions in genotyped subjects. METHODS: Alcohol dependent (AD) subjects received naltrexone alone, placebo alone, disulfiram with placebo or disulfiram with naltrexone. They were genotyped for OPRM1 rs1799971 (Asn40Asp), and DBH rs1611115 (C-1021T). N = 107 male European-American subjects were included. RESULTS: There were no significant interactions with OPRM1. DBH interacted with naltrexone on the primary outcome of abstinence from heavy drinking (χ(2) (1) = 5.23, p = .02). "T" allele carriers on naltrexone had more abstinence compared to "CC" subjects on naltrexone (FET, p = .01). "T" allele carriers on naltrexone had the highest overall rates of abstinence from heavy drinking (>90%). Also, DBH genotype interacted with disulfram (F(1,17) = 7.52, p = .01) on drinks per drinking day with less drinking for subjects with the "CC" genotype than for T allele carriers on disulfiram. CONCLUSIONS: DBH*rs1611115*T associated with better response to naltrexone, while for those on disulfiram that drank, "CC" subjects drank less than T carriers. For rs1799971*G, we did not replicate findings from previous studies showing a more favorable response to NTX, possibly due to the small available sample. SCIENTIFIC SIGNIFICANCE: Genotyping rs1611115 may be useful in understanding inter-individual differences in AD treatment response. FUTURE DIRECTIONS: Further study of rs1611115 pharmacogenetics is warranted.

Problem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics.

OBJECTIVE: Problem opioid use (POU) is a serious public health crisis in the United States. However, little research has examined the prevalence, correlates, and psychiatric characteristics of POU in vulnerable segments of the population, such as US military veterans. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 2441 US veterans. Multivariable logistic regression models were conducted to identify correlates and psychiatric correlates of POU (defined as a positive screen on the Tobacco, Alcohol, Prescription Medication, and Other Substance Use Tool). RESULTS: A total 3.0% (95% confidence interval, 2.0%-4.5%) of US veterans screened positive for POU. Black, non-Hispanic race/ethnicity (odds ratio [OR], 3.83), lifetime alcohol use disorder (OR, 3.38), major depressive disorder (MDD; OR, 2.52), greater number of medical conditions (OR, 1.15), and disability in instrumental activities of daily living (IADL); OR, 1.86) were independently associated with POU. A significant interaction between IADL disability and MDD was observed (OR, 10.73)-among veterans with IADL disability, those with MDD had more than 6-fold greater POU than those without MDD (20.6% vs 3.2%). Furthermore, POU was associated with 2- to 3-folds greater odds of current generalized anxiety disorder and current posttraumatic stress disorder, and lifetime suicide attempt. CONCLUSIONS: POU affects 3.0% of US veterans and is associated with Black race/ethnicity, lifetime physical and mental health morbidities, as well as current psychiatric disorders and lifetime suicide attempts. Results underscore the importance of assessing physical and mental health disorders in veterans at-risk for POU and addressing co-occurring psychiatric disorders associated with POU in this population.

Written exposure therapy for veterans with co-occurring substance use disorders and PTSD: Study design of a randomized clinical trial.

There are high rates of posttraumatic stress disorder (PTSD) among treatment-seeking veterans with substance use disorders (SUD). While addiction programs traditionally do not address PTSD, there is evidence that trauma treatments for individuals with this comorbidity have improved PTSD and SUD outcomes. Written exposure therapy (WET), a five-session evidence-based psychotherapy (EBP) for PTSD, has high patient satisfaction, and lower dropout compared to other EBPs for PTSD. WET may be ideally suited for clinical settings that may not have the trauma expertise found in PTSD specialty clinics, given it requires less training time, treatment sessions, preparation time, and therapist involvement than existing EBPs, and no homework assignments. This paper describes the design, methodology, and protocol of a randomized clinical trial to evaluate whether treatment as usual (TAU) plus WET (n = 51) is superior to TAU plus a neutral topic writing condition (n = 51) on both PTSD and addiction outcomes for veterans in SUD treatment. The primary hypothesis is that participants assigned to TAU+WET, compared to those in TAU+ neutral topic writing, will report reduced symptoms of PTSD. The secondary hypothesis is that veterans receiving WET will have greater decreases in number of days of substance use compared to TAU+ neutral topic controls at follow-up. Assessments will take place at baseline, post-treatment, 8-week, and 12-week follow-up. Exploratory aims will examine the association between heart rate variability and treatment outcomes. If results prove promising, they will support WET as an effective brief, easy to disseminate, adjunct to current SUD treatment for veterans with comorbid PTSD. Trial registration: ClinicalTrials.gov ID NCT05327504.