In the new era of psychedelic assisted therapy: A systematic review of study methodology in randomized controlled trials.

Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics.

A pilot study of stellate ganglion block paired with exposure therapy: Feasibility and acceptability in combat veterans with posttraumatic stress disorder.

BACKGROUND: There is growing evidence that stellate ganglion block (SGB) combined with trauma-focused therapy may help veterans with posttraumatic stress disorder (PTSD) whose symptoms have not responded to traditional treatments. By combining SGB with in vivo exposure, veterans may be more able to fully engage in treatment and see improvement in their overall functioning. OBJECTIVE: The primary aim of this project was to conduct a nonrandomized pilot trial on the feasibility and acceptability of delivering SGB paired with individual psychotherapy to veterans with combat-related PTSD. METHOD: Eligible veterans (N = 14) constructed a hierarchy of in vivo exposure exercises, received the SGB procedure, and attended four additional weekly psychotherapy sessions with a focus on exposure exercises. Participants completed measures at baseline, weekly during treatment, and follow-up assessments immediately posttreatment and 1-month later. RESULTS: The recruitment target was easily met, session attendance was strong, and dropout was relatively low (21.4%). SGB was well tolerated with only mild, transient side effects. Participants reported satisfaction with the treatment they received as measured by the Client Satisfaction Questionnaire (M = 28.8). Paired t test analyses revealed a significant decrease in PTSD symptoms as measured by the PTSD Checklist for DSM-5. We also observed a significant reduction in PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 in mixed models, F(2, 13) = 8.68, p = .004. There were no significant improvements in psychosocial functioning or quality of life. CONCLUSION: SGB paired with psychotherapy is feasible and acceptable to veterans and holds promise for symptom reduction among veterans with combat-related PTSD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions. However, these medications are limited in their efficacy for treating PTSD-AUD comorbidity. Emerging research on the nonclassical psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) suggests that it may be an effective drug used in conjunction with psychotherapy. The following reviews the current research for clinical pharmacotherapies, as well as MDMA-integrative psychotherapy as they pertain to PTSD and AUD in isolation and co-occurrence. Future directions for the role of psychedelic-integrative therapy for the treatment of this comorbidity are discussed.

A randomized clinical trial comparing Interpersonal Psychotherapy with Prolonged Exposure for the treatment of PTSD in veterans.

Trauma-focused therapies are recommended as first-line treatments for posttraumatic stress disorder (PTSD), but many veterans do not complete or sufficiently respond to these treatments. Interpersonal Therapy (IPT) is a non-trauma focused approach that directly addresses the interpersonal and social impairments associated with PTSD. This two-site randomized controlled equivalence trial compared IPT with Prolonged Exposure (PE) in improving PTSD symptoms and interpersonal functioning in 109 veterans with PTSD. Secondary outcomes included functioning and quality of life. We hypothesized that IPT would be statistically equivalent to PE in reducing PTSD symptoms, and superior to PE in improving interpersonal functioning and secondary outcomes of work and social adjustment and quality of life. PTSD symptom severity decreased significantly in both treatments from pre- to post-treatment. Although IPT improved as much as PE and treatments did not differ significantly, the 95 % confidence interval for the difference between the groups did not fall completely within the margin of equivalence. IPT was not superior to PE in improvement in interpersonal functioning or on secondary outcomes. Findings from multi-level linear mixed models using longitudinal data (posttreatment, three and six month follow up) for the primary outcomes of PTSD and interpersonal functioning were consistent with the post-treatment analyses. Although statistically inconclusive in terms of equivalence, the comparable reduction in PTSD symptoms slightly favoring IPT suggests that IPT is an acceptable alternative to gold-standard trauma-focused treatments for veterans with PTSD.

Moral injury as a unique predictor of suicidal ideation in a veteran sample with a substance use disorder.

OBJECTIVE: Suicide among military veterans accounts for 22.2% of all suicide deaths in the United States per year, and veterans with a substance use disorder (SUD) are at an even higher risk for death by suicide. This prevalence has led to increased efforts to identify and investigate both potential risks and protective factors for veterans. This study examines relationships between depression symptomology, exposure to potentially morally injurious events, posttraumatic stress disorder (PTSD) diagnosis, and suicidal ideation, with the primary aim of examining exposure to moral injurious events as a risk factor for suicide in veterans with SUD. METHOD: An inpatient sample of 40 veterans with an active SUD admitted for suicidal ideation was evaluated to examine differences in suicidal ideation, depression symptomology, and exposure to morally injurious events in participants with and without a PTSD diagnosis. Further, exposure to morally injurious events and depression symptomology were examined as predictors of suicidal ideation. RESULTS: Analyses revealed that exposure to morally injurious events (d = 1.72) and depression symptomology (d = 0.72) were higher in participants with a PTSD diagnosis compared to those without a diagnosis, though no significant differences emerged between the two groups on suicidality. A hierarchical regression analysis indicated that only exposure to morally injurious events significantly accounted for variance in suicidality (ß = .31, p = .04, 95% confidence interval [.01, .37]). CONCLUSIONS: These results suggest that although PTSD may be associated with exposure to morally injurious events and depression symptoms, exposure to morally injurious events may potentially lead to higher suicide risk among veterans above and beyond PTSD and depressive symptoms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Brief Report on an 8-Week Course of Mindfulness-based Care for Chronic Pain in the Treatment of Veterans With Back Pain: Barriers Encountered to Treatment Engagement and Lessons Learned.

BACKGROUND: Chronic pain and associated symptoms are debilitating for veterans. Medical costs of treatments are high and current treatment options, most notably with opioid medications, have been associated with significant risk. Mindfulness-based interventions appear promising for chronic pain, but require additional testing in veteran care settings. OBJECTIVE: This project was designed to test the feasibility of engaging and retaining veterans with chronic lower back pain in a new mindfulness protocol tailored for veterans, mindfulness-based care for chronic pain (MBCP). Clinical outcomes were also assessed. DESIGN: An open pilot trial of an 8-week MBCP course that included meditation, gentle yoga, and psychoeducation. SUBJECTS: Twenty-two veterans (mean age=49.77; 18% women) were recruited from a VA Medical Center in the Northeastern US. After screening for inclusion/exclusion criteria, 20 were eligible at baseline. MEASURES: Veterans were assessed at baseline and postintervention for functional impairment, pain intensity and bothersomeness, depression, and mindfulness. RESULTS: The average number of sessions completed was 5; only 4 (20%) attended all sessions. Eleven of the 20 participants (55%) attended 5 or more sessions and had complete preintervention and postintervention visits. Five of the 11 had a clinically meaningful decrease in pain intensity and in depressive symptoms, while 6 of 11 had a meaningful decrease in pain bothersomeness and functional impairment. CONCLUSIONS: It was challenging to enroll and retain participants in this study, even with our intervention designed for veterans. We discuss possible adaptations and refinements in MBCP for veterans with chronic pain to enhance feasibility and improve upon these interventions.

Evaluation of Self-Compassion Focused Group Treatment for Co-Occurring PTSD and Substance Use in Veterans with Posttraumatic Guilt: A Case Study.

Co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUD) following combat exposure affects a significant proportion of military veterans. Guilt and shame are common to PTSD-SUD, suggesting a possible role as a mechanism underlying both disorders. Cultivating self-compassion (SC) among veterans is a logical approach to treating guilt and shame. The purpose of this article is threefold: (a) present scientific theories of SC in the veteran population with emphasis on PTSD, substance use, and guilt and shame; (b) present a case study that highlights how self-compassion-focused treatment (SCFT) can be utilized in a group format with veterans with PTSD-SUD and posttraumatic guilt; and (c) discuss implications of our findings for refining SCFT within a group intervention setting among this population and for future research.

Mechanisms of Behavior Change Within Peer-Implemented Alcohol Interventions.

OBJECTIVE: Colleges continue to experience a high number of referred students because of campus alcohol violations. Subsequently, there has been a trend to use peer-implemented minimal interventions (PMIs), often using motivational interviewing (MI). However, little is known about how PMIs facilitate behavior change. This study aims to examine the mechanisms of behavior change within PMIs and their influence on alcohol reduction among mandated students. METHOD: Participants (N = 146; mean age = 18.7 years; 67% male; 94% White) were college students who violated campus alcohol policy at a Northeastern liberal arts college who received a 15-minute PMI addressing their alcohol use. The Motivational Interviewing Skill Code (Miller et al., 2003) was used to identify peer counselor behaviors that were MI consistent (MICO), client change talk (CT), and client self-exploration. RESULTS: MICO behaviors were positively associated with CT and self-exploration. Client CT and self-exploration were negatively associated with alcohol-related outcomes. Furthermore, mediational models examining MICO behaviors revealed effects for two paths: (a) from MICO to client CT to reduced alcohol use; and (b) from MICO to client self-exploration to reduced alcohol-related consequences and use. CONCLUSIONS: These data support the primary causal chain examining the influence of MICO on in-session client behaviors and related post-session behavior change in PMIs among at-risk students.

Mandated college students' response to sequentially administered alcohol interventions in a randomized clinical trial using stepped care.

OBJECTIVE: Students referred to school administration for alcohol policies violations currently receive a wide variety of interventions. This study examined predictors of response to 2 interventions delivered to mandated college students (N = 598) using a stepped care approach incorporating a peer-delivered 15-min brief advice (BA) session (Step 1) and a 60- to 90-min brief motivational intervention (BMI) delivered by trained interventionists (Step 2). METHOD: Analyses were completed in 2 stages. First, 3 types of variables (screening variables, alcohol-related cognitions, mandated student profile) were examined in a logistic regression model as putative predictors of lower risk drinking (defined as 3 or fewer heavy episodic drinking [HED] episodes and/or 4 or fewer alcohol-related consequences in the past month) 6 weeks following the BA session. Second, we used generalized estimating equations to examine putative moderators of BMI effects on HED and peak blood alcohol content compared with assessment only (AO) control over the 3-, 6-, and 9-month follow-ups. RESULTS: Participants reporting lower scores on the Alcohol Use Disorders Identification Test, more benefits to changing alcohol use, and those who fit the "Bad Incident" profile at baseline were more likely to report lower risk drinking 6 weeks after the BA session. Moderation analyses revealed that Bad Incident students who received the BMI reported more HED at 9-month follow-up than those who received AO. CONCLUSION: Current alcohol use as well as personal reaction to the referral event may have clinical utility in identifying which mandated students benefit from treatments of varying content and intensity.

Response of heavy-drinking voluntary and mandated college students to a peer-led brief motivational intervention addressing alcohol use.

Little is known about the way in which mandated and heavy-drinking voluntary students comparatively respond to peer-led brief motivational interventions (BMIs) and the mediators and moderators of intervention effects. Research suggests that mandated students may be more defensive due to their involvement in treatment against their will and this defensiveness, in turn, may relate to treatment outcome. Furthermore, it is not clear how mandated and heavy-drinking voluntary students perceived satisfaction with peer-led BMIs relates to treatment outcomes. Using data from two separate randomized controlled trials, heavy drinking college students (heavy-drinking voluntary, n = 156; mandated, n = 82) completed a peer-led brief motivational intervention (BMI). Both mandated and heavy-drinking volunteer students significantly reduced drinking behaviors at 3-month follow-up, reported high levels of post-intervention session satisfaction, yet no effects for mediation or moderation were found. Findings offer continued support for using peer counselors to deliver BMIs; however, results regarding the mechanisms of change were in contrast to previous findings. Implications for treatment and future areas of research are discussed.

Integrated Cognitive Behavioral Therapy (ICBT) For PTSD and Substance Use in Iraq and Afghanistan Veterans: A Feasibility Study.

Co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) is prevalent in military Veterans and is associated with poorer outcomes than either disorder alone. The current pilot study examines the feasibility of delivering integrated cognitive behavioral therapy (ICBT) for co-occurring PTSD-SUD to Veterans who served in Iraq and Afghanistan. Our primary aims were testing the feasibility of engaging and retaining Veterans with a complex clinical presentation in a 12-week structured therapy. We focused on two feasibility outcomes: 1) acceptability; and 2) tolerability. We also examined clinically meaningful change in PTSD and depressive symptoms as a secondary aim. Over the course of the study, we recruited 12 eligible Veterans, 6 of whom completed ICBT. We encountered challenges related to engaging and retaining Veterans in treatment and discuss adaptations and refinements of ICBT or other integrated treatments for returning Veterans with co-occurring PTSD-SUD to increase feasibility with military Veterans.