The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against. METHODS: Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed. RECOMMENDATIONS: The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals' health outcomes and quality of life.

Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD.

AIMS: The main objective of the study was to compare the differences in craving following trauma and stress scripts in individuals with alcohol dependence (AD) who have experienced trauma but did not meet criteria for post-traumatic stress disorder (PTSD). METHODS: Twenty-eight men and women who participated in a treatment trial were included in this study before starting treatment. All had to meet criteria for AD and had experienced trauma at some point of their lives but were never diagnosed with PTSD. All participants had one laboratory session and were exposed to stress, trauma and neutral scripts randomly assigned. Main measures of craving, anxiety and mood were administered before, during and after each script. RESULTS: Stress and trauma scripts induced significantly more craving and anxiety than the neutral scripts. Interestingly, stress scripts produced stronger craving and anxiety than the trauma scripts but only with some measures. Stress and trauma scripts produced significantly more fear, anger and sadness and significantly lower ratings of joy and relaxation than the neutral script. Again, there were no differences between stress and trauma scripts for any of the emotional subscales. CONCLUSIONS: Trauma scripts did not result in stronger craving than stress scripts. These findings suggest that trauma in the absence of PTSD diagnosis does not lead to stronger craving for alcohol.

Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

BACKGROUND: Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. METHODS: Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. RESULTS: Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. CONCLUSIONS: The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the importance of adequate treatment of PTSD as reactivity related to trauma cues and reminders may be an important factor in craving and relapse.

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.

PTSD and comorbid AUD: a review of pharmacological and alternative treatment options.

BACKGROUND: Although posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) frequently co-occur there are no specific treatments for individuals diagnosed with these comorbid conditions. The main objectives of this paper are to review the literature on pharmacological options for PTSD and comorbid AUD, and to summarize promising behavioral and alternative interventions for those with these dual diagnoses. METHODS: We conducted a comprehensive search on PsycINFO and MEDLINE/PubMed databases using Medical Subject Headings terms in various combinations to identify articles that used pharmacotherapy for individuals with dual diagnoses of PTSD and AUD. Similar strategies were used to identify articles on behavioral and alternative treatments for AUD and PTSD. We identified and reviewed six studies that tested pharmacological treatments for patients with PTSD and comorbid AUD. RESULTS: The literature on treatment with US Food and Drug Administration approved medications for patients with dual diagnosis of PTSD and AUD is very limited and inconclusive. Promising evidence indicates that topiramate and prazosin may be effective in reducing PTSD and AUD symptoms in individuals with comorbidity. Seeking safety has had mixed efficacy in clinical trials. The efficacy of other behavioral and alternative treatments (mindfulness-based, yoga, and acupuncture) is more difficult to evaluate since the evidence comes from small, single studies without comparison groups. CONCLUSION: There is a clear need for more systematic and rigorous study of pharmacological, behavioral, and alternative treatments for patients with dual diagnoses of PTSD and AUD.

Novel pharmacological approaches to drug abuse treatment.

The field of pharmacologic addiction treatment is expanding rapidly. While there are currently several FDA-approved medications for nicotine, alcohol, and opiate dependence, research into novel pharmacological approaches for these and additional substances is legion. Each drug of abuse, while sharing a common final neural pathway of increasing dopaminergic tone, has unique and individual characteristics that are important in developing improved and varied treatments. In this chapter, we discuss such research and present the neurobiological underpinnings of these explorations. In general, addiction treatment is focused on four areas: (1) reducing withdrawal discomfort, (2) diminishing cravings, (3) blocking rewarding effects of the drug, and (4) treating comorbidities, such as depression or ADHD. We present current ideas in pharmacologic research for nicotine, alcohol, cannabis, stimulants, and opiates.

Absence of significant interactive effects of high-dose D-cycloserine and ethanol in healthy human subjects: preliminary insights into ethanol actions at the glycine B site of NMDA glutamate receptors.

BACKGROUND: Ethanol reduces N-methyl-d-aspartate (NMDA) glutamate receptor function via multiple cellular targets. It is not yet clear whether direct ethanol antagonism of the glycine(B) co-agonist site of NMDA receptors is relevant to this effect. The purpose of this study was to evaluate whether ethanol effects at the glycine(B) co-agonist site was clinically relevant by evaluating some aspects of the psychopharmacologic interactions between the glycine(B) partial agonist, D-cycloserine (DCS), and ethanol in healthy human subjects. METHODS: All subjects completed 4 test days under double-blind conditions in which DCS or placebo was administered orally prior to ethanol or an ethanol-tainted placebo drink. Two groups of healthy subjects were studied. A first group of subjects (n = 25) were pretreated orally with DCS 500 mg or placebo 4 hours prior to ethanol (0.8 g/kg, p.o. or placebo) administration. A second group of subjects (n = 20) were pretreated with DCS 1000 mg or placebo prior to ethanol administration. Outcomes included subjective and cognitive responses to the experimental interventions. RESULTS: Predictable ethanol responses were observed in both groups of subjects, although the response to ethanol and the breath alcohol levels, but not plasma alcohol levels, were slightly but significantly lower in the group that received the higher DCS dose. DCS produced mild sedative effects that were greater for the lower than the higher dose. It also produced a mild impairment of verbal fluency without impairing attention. No statistically significant interactions between ethanol and DCS emerged in analyses. However, the combination of ethanol and DCS produced significantly greater impairment than both ethanol or DCS administered alone on a test of verbal fluency and aspects of memory function. IMPLICATIONS: DCS and ethanol both produced sedative and cognitive effects, consistent with their ability to reduce NMDA receptor function. However, the absence of interactive effects observed in this study raises questions about the clinical significance of the glycine(B) site as a target for ethanol in the brain at levels of ethanol intoxication associated with social drinking. However, it should be noted that this conclusion is limited to the dependent measures evaluated and the doses of ethanol and DCS studied.