Posttraumatic stress disorder and alcohol use disorder in women

Trauma-focused treatments are effective for posttraumatic stress disorder (PTSD) but are rarely offered to patients with comorbid substance use disorder. Research suggests gender-based differences in prevalence and treatment needs for these patients, but treatment trials have mainly included men. To evaluate whether integrated trauma-focused psychological treatment (ie, integrated treatment) leads to greater reduction in PTSD symptom severity and weekly alcohol use than usual treatment (ie, relapse prevention) for alcohol use disorder (AUD) in women. This randomized clinical trial was conducted at 3 outpatient addiction services in Sweden. Data were collected from 2016 to 2021, and participants were followed up for 9 months after treatment initiation. Data were analyzed from October 2024 to April 2025. Participants were women older than 18 years with current PTSD and moderate-to-severe AUD diagnoses meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Participants were randomly assigned to either the integrated treatment or relapse prevention arm. Intention-to-treat analyses were carried out using linear mixed models. Twelve sessions, typically weekly, of integrated treatment (ie, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure [COPE]) or relapse prevention were delivered by trained and experienced staff (including registered nurses, licensed psychologists, and social workers). Prespecified co-primary outcomes were PTSD symptom severity (assessed by blinded raters using Clinician-Administered PTSD Scale for DSM-5 [CAPS-5]) and weekly alcohol use (self-assessed using Timeline Followback) from baseline to the 9-month follow-up. Secondary outcomes included self-reported PTSD symptom severity, clinician-rated PTSD remission, and an objective biomarker of alcohol use (phosphatidylethanol level). Ninety women (mean [SD] age, 44.7 [12.5] years) were included and randomly assigned to integrated treatment (n = 45) or relapse prevention (n = 45). In both arms, PTSD symptom severity decreased from baseline to 9-month follow-up (mean CAPS-5 score for integrated treatment: 37.40 [95% CI, 33.84-40.96] to 13.18 [95% CI, 8.95-17.41]; relapse prevention: 39.09 [95% CI, 35.53-42.65] to 23.68 [95% CI, 19.47-27.88]), with a significantly greater decrease in the integrated treatment arm than the relapse prevention arm (treatment-by-time interaction: F4,155 = 3.0; P = .02). Self-reported alcohol use decreased significantly over time (F14,581 = 3.0; P < .001) in both arms (integrated treatment: 144.41 [95% CI, 104.66-184.15] g/week to 92.65 [95% CI, 48.81-136.48] g/week; relapse prevention: 133.45 [95% CI, 93.71-173.19] g/week to 77.80 [95% CI, 31.65-123.95] g/week), but there was no detectable difference between treatments. In this trial of integrated treatment vs relapse prevention, integrated treatment led to a greater reduction in PTSD symptom severity and no detectable difference in alcohol use decrease compared with relapse prevention. These results support that integrated treatment can safely and effectively treat PTSD in women with AUD and ongoing alcohol use. ISRCTN.org Identifier: ISRCTN61391164.

Clinical Characteristics and Health Service Use of Veterans With Comorbid Bipolar Disorder and PTSD

Dr. Jones declares no conflict of interests. Dr. Back is the first author of a behavioral therapy targeting the treatment of substance use disorder and comorbid PTSD.

ABSTRACTBackground: Alcohol use disorder (AUD) is a serious psychiatric disorder with medical, psychiatric, and social consequences. In individuals with comorbid post-traumatic stress disorder (PTSD), treatment outcomes are notably worse in comparison with treatment outcomes associated with either disorder occurring alone. There is a growing literature evaluating treatments, both pharmacotherapy and psychotherapy focused, in individuals with co-occurring AUD and PTSD. The main objective of this review was to evaluate pharmacotherapy and psychotherapy studies that were specifically designed to evaluate the treatment of individuals with comorbid AUD and PTSD. Method: MEDLINE and PUBMED databases were searched with no specific time period. Studies focusing on SUD treatments were excluded. Because the number of random clinical trial (RCT) studies was small, all publications (including open label, single case, and secondary analyses) were included. Results: Sixteen studies met criteria and were organized based on whether they evaluated the efficacy of pharmacotherapy, psychotherapy, or both. Pharmacological interventions with either AUD or PTSD agents were mainly effective in reducing drinking outcomes; only one study using sertraline found that the active study medication was superior to placebo in reducing PTSD symptoms. Psychotherapies were not superior to a comparative treatment in reducing drinking outcomes. Only 1 study showed reduction in PTSD symptoms in a small sample of completers. The single RCT that evaluated the efficacy of naltrexone in combination with psychotherapies (prolonged exposure or supportive counseling) found that naltrexone in combination with prolonged exposure was better for drinking outcomes at follow-up. Conclusions: Although these studies represent a good start in terms of research in treatment interventions of co-occurring AUD and PTSD, the studies are very limited, most lack adequate power, and the majority suffer from inadequate control groups. In particular, there is a strong need to develop and evaluate the combined medication and psychological-based treatment interventions for those with comorbid AUD and PTSD.

We studied 13 U.S. male military veterans and their female partners who consented to participate in an uncontrolled trial of couple treatment for alcohol use disorder and posttraumatic stress disorder (CTAP). CTAP is a 15-session, manualized therapy, integrating behavioral couples therapy for alcohol use disorder (AUD) with cognitive-behavioral conjoint therapy for posttraumatic stress disorder (PTSD). Due to ineligibility (n = 1) and attrition (n = 3), 9 couples completed the study, and 7 completed 12 or more sessions. There were 8 veterans who showed clinically reliable pre- to posttreatment reduction of PTSD outcomes. There were also significant group-level reductions in clinician-, veteran-, and partner-rated PTSD symptoms (d = 0.94 to 1.71). Most veterans showed clinically reliable reductions in percentage days of heavy drinking. Group-level reduction in veterans' percentage days of heavy drinking was significant (d = 1.01). There were 4 veterans and 3 partners with clinically reliable reductions in depression, and group-level change was significant for veterans (d = 0.93) and partners (d = 1.06). On relationship satisfaction, 3 veterans and 4 partners had reliable improvements, and 2 veterans and 1 partner had reliable deterioration. Group-level findings were nonsignificant for veteran relationship satisfaction (d = 0.26) and for partners (d = 0.52). These findings indicate that CTAP may be a promising intervention for individuals with comorbid PTSD and AUD who have relationship partners.

Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both disorders. Several neurobiological systems have been implicated in the development and maintenance of AUD and PTSD, and pharmacologic interventions targeting these systems for singular diagnoses of AUD or PTSD have proven effective. However, there are no established treatments for co-occurring AUD and PTSD, and relatively few studies have examined potential pharmacotherapy for treating symptoms of both AUD and PTSD in comorbid populations. This review provides a brief overview of the studies to date on pharmacotherapeutic treatment interventions for comorbid AUD and PTSD and highlights future directions for promising targets that have potential in the treatment of individuals with this dual diagnosis. Clinical implications of these findings are also discussed. While current medications targeting the opioidergic, noradrenergic, serotonergic, and GABAergic/glutamatergic brain systems are only modestly efficacious in improving symptoms in individuals with comorbid AUD and PTSD, novel targets within these neurobiological systems may be clinically useful for treating alcohol use outcomes and PTSD symptom severity. More work is needed to optimize pharmacologic treatment strategies that target both alcohol-motivated behavior and PTSD-related symptoms in individuals with co-occurring AUD and PTSD.

ABSTRACTObjective: Negative affect intensity and hostility have both been implicated in alcohol use disorders (AUD) and posttraumatic stress disorder (PTSD) when they occur separately, but neither have been compared or explored among those with comorbid AUD and PTSD. This study is a secondary analysis designed to compare levels of negative affect intensity and hostility among those with AUD to those with comorbid AUD and PTSD. Methods: Participants (n = 113) were recruited from the placebo-controlled groups of two distinct 12-week clinical trials (NCT00342563 and NCT00744055). The Short Affect Intensity Scale and Buss-Durkee Hostility Inventory were administered at weeks 0, 4, 8, and 12 to all study participants to assess negative affect intensity and hostility levels, respectively. Results: Individuals with comorbid AUD and PTSD showed significantly higher levels of negative affect intensity and hostility than individuals with AUD only. These levels remained relatively stable over the course of the study in spite of all study participants showing clinically significant improvements in AUD severity and PTSD symptomatology (for those with dual diagnosis). Conclusions: Our results indicate that individuals with comorbid AUD and PTSD have higher levels of negative affect and higher levels of hostility compared to individuals with AUD alone. In addition, these heightened levels of negative affect intensity and hostility appear to function somewhat independently of diagnosis severity and symptomatology improvement. To our knowledge, this is the first study to compare negative affect intensity and hostility levels between individuals with AUD alone and those with comorbid AUD and PTSD.

Converging lines of evidence suggest that individuals with comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) may be characterized by heightened defensive reactivity, which serves to maintain drinking behaviors and anxiety/hyperarousal symptoms. However, it is important to note that very few studies have directly tested whether individuals with PTSD and AUD exhibit greater defensive reactivity compared with individuals with PTSD without AUD. Therefore, the aim of the current study was to test this emerging hypothesis by examining individual differences in error-related negativity (ERN), an event-related component that is larger among anxious individuals and is thought to reflect defensive reactivity to errors. Participants were 66 military veterans who completed a well-validated flanker task known to robustly elicit the ERN. Veterans were comprised of 3 groups: controls (i.e., no PTSD or AUD), PTSD-AUD (i.e., current PTSD but no AUD), and PTSD + AUD (i.e., current comorbid PTSD and AUD). Results indicated that individuals with PTSD and controls generally did not differ in ERN amplitude. However, among individuals with PTSD, those with comorbid AUD had significantly larger ERNs than those without AUD. These findings suggest that PTSD + AUD is a neurobiologically unique subtype of PTSD, and the comorbidity of AUD may enhance defensive reactivity to errors in individuals with PTSD. (PsycINFO Database Record

Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.

Although some studies have demonstrated residual symptoms in patients who have participated in posttraumatic stress disorder (PTSD) treatment, no studies to date have assessed residual PTSD symptoms following treatment for comorbid alcohol use disorder (AUD) and PTSD (PTSD/AUD). We examined residual symptoms of PTSD and AUD in 73 veterans with PTSD/AUD who completed a posttreatment assessment after being randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) or Seeking Safety (SS). We used logistic regression to identify differences (a) in residual PTSD and AUD symptoms among participants randomized to COPE versus SS and (b) among those with versus without a posttreatment PTSD/AUD diagnosis within both treatment conditions. Participants randomized to SS were more likely to report persistent avoidance, inability to experience positive emotions, hypervigilance, difficulty concentrating, and difficulty sleeping, ORs = 3.74-6.21. There were no differences between COPE and SS regarding the likelihood of persistent AUD symptoms. Participants without a posttreatment PTSD diagnosis had lower conditional probabilities of most symptoms, although exaggerated startle, OR = 0.71, and irritability/aggression, OR = 0.58, were most likely to persist. Participants without a posttreatment AUD diagnosis had lower conditional probabilities of most symptoms, although withdrawal, OR = 0.21; unsuccessful quit attempts, OR = 0.04; and higher intake, OR = 0.01, were most likely to persist. Findings indicate hyperarousal may warrant additional intervention following PTSD treatment. Residual AUD symptoms may relate to the enduring nature of some AUD symptoms rather than a lack of treatment efficacy.

Comorbid alcohol use and post-traumatic stress disorders: Pharmacotherapy with aldehyde dehydrogenase 2 inhibitors versus current agents

Cognitive Processing Therapy for veterans with comorbid PTSD and alcohol use disorders

Little is known about gender differences in healthcare use among newly returning veterans with posttraumatic stress disorder (PTSD). We investigated gender differences in Veterans Affairs (VA) medical center health service use among Iraq and Afghanistan veterans with PTSD with and without comorbid depression and alcohol use disorders (AUD). Using VA administrative data, bivariate and multivariate statistics were used to examine gender differences in health service use among 159,705 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with PTSD seeking VA healthcare from October 7, 2001, to December 31, 2010. Female veterans with PTSD were more likely to be black and single and to have higher mental health, primary care, and emergency care use compared to men with PTSD. Men were more likely to have higher mental health inpatient use compared to women. Women and men with comorbid PTSD and depression or comorbid PTSD and AUD were more likely to have higher use in all domains compared to their counterparts with PTSD without these comorbid disorders. Women with comorbid PTSD and depression were 12.5 times more likely to have a mental health inpatient hospitalization compared to their female counterparts without depression and twice as likely to have a mental health hospitalization compared to men with comorbid PTSD and depression. Women with PTSD had higher use than men in almost all areas, as did all veterans with comorbid PTSD and depression and comorbid PTSD and AUD, regardless of gender. Better understanding these health service use differences will allow for targeted evaluation and integrated treatment interventions in veterans with PTSD.

There is concern that exposure therapy, an evidence-based cognitive-behavioral treatment for posttraumatic stress disorder (PTSD), may be inappropriate because of risk of relapse for patients with co-occurring substance dependence. To determine whether an integrated treatment for PTSD and substance dependence, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), can achieve greater reductions in PTSD and substance dependence symptom severity compared with usual treatment for substance dependence. Randomized controlled trial enrolling 103 participants who met DSM-IV-TR criteria for both PTSD and substance dependence. Participants were recruited from 2007-2009 in Sydney, Australia; outcomes were assessed at 9 months postbaseline, with interim measures collected at 6 weeks and 3 months postbaseline. Participants were randomized to receive COPE plus usual treatment (n = 55) or usual treatment alone (control) (n = 48). COPE consists of 13 individual 90-minute sessions (ie, 19.5 hours) with a clinical psychologist. Change in PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS; scale range, 0-240) and change in severity of substance dependence as measured by the number of dependence criteria met according to the Composite International Diagnostic Interview version 3.0 (CIDI; range, 0-7), from baseline to 9-month follow-up. A change of 15 points on the CAPS scale and 1 dependence criterion on the CIDI were considered clinically significant. From baseline to 9-month follow-up, significant reductions in PTSD symptom severity were found for both the treatment group (mean difference, -38.24 [95% CI, -47.93 to -28.54]) and the control group (mean difference, -22.14 [95% CI, -30.33 to -13.95]); however, the treatment group demonstrated a significantly greater reduction in PTSD symptom severity (mean difference, -16.09 [95% CI, -29.00 to -3.19]). No significant between-group difference was found in relation to improvement in severity of substance dependence (0.43 vs 0.52; incidence rate ratio, 0.85 [95% CI, 0.60 to 1.21), nor were there any significant between-group differences in relation to changes in substance use, depression, or anxiety. Among patients with PTSD and substance dependence, the combined use of COPE plus usual treatment, compared with usual treatment alone, resulted in improvement in PTSD symptom severity without an increase in severity of substance dependence. isrctn.org Identifier: ISRCTN12908171.

S274. Neural Circuit Mechanisms of Stress-Induced Excessive Alcohol Consumption