Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis.

OBJECTIVE: The primary aim of this qualitative study was to delineate psychological mechanisms of change in the first randomized controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder (AUD). Theories regarding psychological processes involved in psychedelic therapy remain underdeveloped. METHOD: Participants (N = 13) mostly identified as non-Hispanic and White, with approximately equal proportions of cisgender men and women. Participants engaged in semistructured interviews about their subjective experiences in the study. Questions probed the nature of participants' drinking before and after the study as well as coping patterns in response to strong emotions, stress, and cravings for alcohol. Verbatim transcripts were coded using Dedoose software, and content was analyzed with interpretive phenomenological analysis. RESULTS: Participants reported that the psilocybin treatment helped them process emotions related to painful past events and helped promote states of self-compassion, self-awareness, and feelings of interconnectedness. The acute states during the psilocybin sessions were described as laying the foundation for developing more self-compassionate regulation of negative affect. Participants also described newfound feelings of belonging and an improved quality of relationships following the treatment. CONCLUSION: Our results support the assertion that psilocybin increases the malleability of self-related processing, and diminishes shame-based and self-critical thought patterns while improving affect regulation and reducing alcohol cravings. These findings suggest that psychosocial treatments that integrate self-compassion training with psychedelic therapy may serve as a useful tool for enhancing psychological outcomes in the treatment of AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Improvement in quality of life among women and men aged 60 years and older following treatment for alcohol use disorder.

BACKGROUND: Previous studies have yielded mixed results on the association between gender and alcohol use disorder (AUD) treatment outcomes. Thus, additional research is needed to determine the effect of gender on AUD treatment outcomes, including quality of life (QoL), particularly among older adults. AIMS: In a clinical sample of older adults with DSM-5 AUD, we examined changes in QoL from the beginning of AUD treatment through 1 year of follow-ups. We also examined the effect of gender and explored interaction effects with gender on QoL. METHODS: We utilized data from the "Elderly Study," a multi-national, single-blind, randomized, controlled trial of 693 adults aged 60+ with DSM-5 AUD. Alcohol use was assessed with the Form-90, and QoL with the brief version of the World Health Organization QoL measure. Information was collected at treatment initiation and at 4-, 12-, 26-, and 52-week follow-ups. Multilevel mixed-effects logistic and linear regression models were used to examine QoL changes and the effect of gender on changes in QoL. RESULTS: Following treatment, small, but significant improvements were seen over time in overall perceived health (p < 0.05). Improvements that persisted over the 1-year follow-up period were seen in the QoL domains of physical health (ß: 2.6, 95% CI: 1.4-3.9), psychological health (ß: 3.5, 95% CI: 3.3-3.8), social relationships (ß: 4.0, 95% CI: 2.5-5.6), and environmental health (ß: 1.4, 95% CI: 0.4-2.4). No significant changes were seen over time in overall perceived QoL (p = 0.58). Gender was not associated with changes in any of the QoL outcome measures (all p ≥ 0.05). CONCLUSIONS: Among 60+ year-old adults receiving treatment for DSM-5 AUD, improvements in QoL were achievable and maintained over time, but were not associated with gender.

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression or provide substantial clinical benefit. Furthermore, despite psychological distress being highly prevalent in ALS patients, psychological treatments remain understudied. Psychedelics (i.e., serotonergic psychedelics and related compounds like ketamine) have seen a resurgence of research into therapeutic applications for treating a multitude of neuropsychiatric conditions, including psychiatric and existential distress in life-threatening illnesses. Methods: We conducted a narrative review to examine the potential of psychedelic assisted-psychotherapy (PAP) to alleviate psychiatric and psychospiritual distress in ALS. We also discussed the safety of using psychedelics in this population and proposed putative neurobiological mechanisms that may therapeutically intervene on ALS neuropathology. Results: PAP has the potential to treat psychological dimensions and may also intervene on neuropathological dimensions of ALS. Robust improvements in psychiatric and psychospiritual distress from PAP in other populations provide a strong rationale for utilizing this therapy to treat ALS-related psychiatric and existential distress. Furthermore, relevant neuroprotective properties of psychedelics warrant future preclinical trials to investigate this area in ALS models. Conclusion: PAP has the potential to serve as an effective treatment in ALS. Given the lack of effective treatment options, researchers should rigorously explore this therapy for ALS in future trials.

Optimizing Recruitment and Retention in Substance Use Disorder Research in Emergency Departments.

INTRODUCTION: Clinical trial recruitment and retention of individuals who use substances are challenging in any setting and can be particularly difficult in emergency department (ED) settings. This article discusses strategies for optimizing recruitment and retention in substance use research conducted in EDs. METHODS: Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED) was a National Drug Abuse Treatment Clinical Trials Network (CTN) protocol designed to assess the impact of a brief intervention with individuals screening positive for moderate to severe problems related to use of non-alcohol, non-nicotine drugs. We implemented a multisite, randomized clinical trial at six academic EDs in the United States and leveraged a variety of methods to successfully recruit and retain study participants throughout the 12-month study course. Recruitment and retention success is attributed to appropriate site selection, leveraging technology, and gathering adequate contact information from participants at their initial study visit. RESULTS: The SMART-ED recruited 1,285 adult ED patients and attained follow-up rates of 88%, 86%, and 81% at the 3-, 6-, and 12-month follow-up periods, respectively. Participant retention protocols and practices were key tools in this longitudinal study that required continuous monitoring, innovation, and adaptation to ensure strategies remained culturally sensitive and context appropriate through the duration of the study. CONCLUSION: Tailored strategies that consider the demographic characteristics and region of recruitment and retention are necessary for ED-based longitudinal studies involving patients with substance use disorders.

A Systematic Approach to Standardizing Drinking Outcomes From Timeline Followback Data.

Objective: The timeline followback (TLFB) interview is the gold standard for the quantitative assessment of alcohol use. However, self-reported "drinks" can vary in alcohol content. If this variability is not accounted for, it can compromise the reliability and validity of TLFB data. To improve the precision of the TLFB data, we developed a detailed standard operating procedure (SOP) to calculate standard drinks more accurately from participant reports. Method: For the new SOP, the volume and alcohol content by volume (ABV) of distinct types of alcoholic beverages were determined based on product websites and other reliable sources. Recipes for specific cocktails were constructed based on recipes from bartending education websites. One standard drink was defined as 0.6 oz (14 g) of absolute alcohol. Standard drink totals were contrasted for the new SOP approach and the standard procedure, which generally assumed that one self-reported drink was equivalent to one standard drink. Results: Relative to the standard TLFB procedure, higher numbers of standard drinks were reported after implementing the TLFB SOP. Conclusions: Variability in procedures for conversion of self-reported alcohol consumption to standard drinks can confound the interpretation of TLFB data. The use and reporting of a detailed SOP can significantly reduce the potential for such inconsistencies. Detailed and consistent procedures for calculation of standard drinks can enhance the quality of TLFB drinking data.

Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous µ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial.

Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

Comparison of self-reported alcohol consumption and ethyl glucuronide in hair in a sample of 60+ year -olds treated for DSM-5 alcohol use disorder.

There is a lack of evidence for the consistency between self-reported alcohol consumption (SRAC) and concentrations of ethyl glucuronide in hair (hEtG) among elderly patients treated exclusively for alcohol use disorder (AUD). Hence, this study assessed the consistency between these two measures in these patients. A total of 190 patients with AUD were assessed for SRAC using Form 90 and hEtG, 14 or 22 weeks after treatment conclusion. Patients were grouped according to SRAC (g/day) and corresponding hEtG concentrations (pg/mg): 0 and <5 (abstinence), 0.1-14.3 and 5.0-9.9 (low consumption), 14.4-21.4 and 10.0-15.9 (moderate consumption), 21.5-59.9 and 16.0-30 (high consumption) and ≥60 and >30 (excessive consumption). The extent of underreporting and overreporting was examined by crosstabulations, and inter-rater reliability was reported by kappa correlations. Associations and effect modification were examined by conditional logistic regression. Due to multitesting, p-values ≤0.01 were considered significant. Underreporting was found in 96 patients (50.5%) and overreporting in 41 patients (21.6%). The kappa coefficients varied between 0.19 and 0.34. HEtG was more likely to detect low, moderate and high alcohol consumption compared with SRAC (ORs between 5.1 and 12.6, all p-values <0.01), but SRAC and hEtG did not differ significantly with respect to identification of abstinence (OR = 1.9, p = 0.05). Inconsistency between the outcome measures was found in a considerable number of the patients. More studies examining the consistency between SRAC and specific direct biomarkers of alcohol in this population seem warranted.

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.

A randomized clinical trial of strengths-based case management to link emergency department patients to opioid use disorder treatment.

BACKGROUND: Despite the existence of effective pharmacotherapies, rates of opioid use disorder and opioid overdose deaths have continued to increase. Emergency department (ED) visits provide an important opportunity to engage in treatment patients with untreated opioid use disorder (OUD). Case management implemented in other settings is effective in linking those with opioid and other drug use disorders to longer-term treatment, but research has not established its efficacy in the ED. Here we report the results of a trial of Strengths-Based Case Management (SBCM) for people with untreated OUD who are identified during ED visits, with the primary goal of linking them to pharmacologic treatment. METHODS: The study identified patients with untreated OUD during a treatment episode at a large urban ED. The study randomly assigned three hundred participants in 1:1 ratio to receive SBCM or screening, assessment, and referral (SAR) to OUD treatment. Those assigned to SBCM received up to six sessions of SBCM with the primary goal of linkage to treatment. Primary outcomes were initiation of treatment and engagement in pharmacotherapy for OUD. The study defined a "successful outcome" for opioid use as a 3-month urine negative for illicit opioids and no more than 2 days of self-reported opioid misuse in the 4 weeks prior to the 3-month interview. RESULTS: Rates of treatment initiation were not significantly different in the SBCM and SAR groups (57.4% vs. 49.7%, respectively, p > 0.05), nor did engagement in pharmacotherapy differ significantly between groups (p > 0.05). During the 90 days following the index ED visit, SBCM and SAR participants engaged in pharmacotherapy for a mean of 21.8% (SD = 35.1%) versus 17.7% (SD = 31.0%) of days, respectively. Likewise, no significant difference occurred between groups in rates of "successful opioid use outcome" as defined a priori (p > 0.05), although self-reported opioid use over the entire 6-month follow-up period was lower in the SBCM group (10.8 vs. 13.4 days/month, p = 0.042). CONCLUSIONS: SBCM-ED did not improve OUD treatment initiation and engagement in this ED study. Although these findings do not necessarily generalize to all EDs, other approaches, such as direct referral or initiation of treatment in the ED, have considerable empirical support, and should be implemented where they are feasible.

The Prognostic Role of DSM-5 Alcohol Use Disorder Severity and Age of Onset in Treatment Outcome Among Adults Aged 60.

AIMS: To investigate among older adults with DSM-5 alcohol use disorder (AUD) the relevance of (1) baseline DSM-5 AUD severity, (2) age of DSM-5 AUD onset, and (3) the interactions of DSM-5 AUD severity*treatment condition and age of DSM-5 AUD onset*treatment condition for the prediction of AUD treatment outcomes. METHODS: The international multicenter RCT "ELDERLY-Study" compared outpatient motivational enhancement therapy (4 sessions) with outpatient motivational enhancement therapy followed by community reinforcement approach for seniors (8 sessions) in adults aged 60+ with DSM-5 AUD. Baseline and 1-, 3-, and 6-month follow-up data from the German and Danish ELDERLY-sites (n = 544) were used (6-month participation rate: 75.9%). DSM-5 AUD diagnoses were obtained using the Mini International Neuropsychiatric Interview and alcohol use using Form 90. Associations between DSM-5 AUD severity and age of onset and AUD treatment outcomes were investigated using multiple logistic regression and generalized linear models. RESULTS: The sample was diverse in AUD severity (severe: 54.9%, moderate: 28.2%, mild: 16.9%) and age of onset (median: 50 years; 12-78 years). Overall, with few exceptions, neither AUD severity, nor age of onset, nor their respective interactions with treatment condition significantly predicted drinking outcomes at the different follow-ups ( P ≥ 0.05). CONCLUSIONS: No indication was found for the need to tailor treatment content according to DSM-5 AUD severity and earlier onset in older adults.

Residual alcohol use disorder symptoms after treatment predict long-term drinking outcomes in seniors with DSM-5 alcohol use disorder.

BACKGROUND: Risk of relapse within the first months after alcohol use disorder (AUD) interventions is substantial among older adults. For this vulnerable group, little information exists on how this risk is associated with residual DSM-5 AUD symptoms after treatment. AIMS: To investigate among older adults who received short-term treatment for DSM-5 AUD (1) the prediction of drinking behaviors and quality of life 12 months after treatment initiation by 6-month DSM-5 AUD symptoms, AUD severity, and AUD remission, and (2) whether these DSM-5 AUD indicators provide prognostic information beyond that gained from 6-month alcohol use (AU) status. METHODS: The international multicenter RCT "ELDERLY-Study" enrolled adults aged 60+ with DSM-5 AUD. We used data from the subsample of 323 German and Danish participants with complete DSM-5 AUD criterion information 6 months after treatment initiation (61% male; mean age = 65.5 years). AU was assessed with Form 90, DSM-5 AUD with the M.I.N.I., and quality of life with the WHOQOL-BREF. Generalized linear models were applied to investigate the associations between 6-month AUD indicators and 12-month AU and quality of life. RESULTS: Independent of AU at 6 months, having 1 (vs. no) residual AUD symptom at 6 months predicted a 12-month "slip," defined as exceeding a blood alcohol concentration of 0.05% at least once during that time (OR: 3.7, 95% CI: 1.5 to 9.0), heavy episodic drinking, and hazardous use (p < 0.05). AUD remission was associated with a lower risk of a "slip" at 12 months (p < 0.05). Failed reduction/cessation was associated with poorer physical health (Coef.: -0.4, 95% CI -0.7 to -0.1). CONCLUSION: For older adults, residual AUD symptoms in the first months after short-term treatment predict problematic AU outcomes during the first 12 months after treatment entry. Thus, residual symptoms should be addressed in this patient population during posttreatment screenings.

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

Stability of Posttreatment Reductions in World Health Organization (WHO) Drinking Risk Levels and Posttreatment Functioning in Older Adults with DSM-5 Alcohol Use Disorder: Secondary Data Analysis of the Elderly Study.

BACKGROUND: Studies have found that reductions in World Health Organization (WHO) drinking risk levels may be a stable outcome of treatment for alcohol use disorder (AUD) and associated with functional improvements. The aim of this study was to investigate whether posttreatment reductions in WHO drinking risk levels are stable over time among older adults and associated with a decrease in consequences of drinking and AUD symptoms and improved quality of life. METHODS: Participants. Individuals 60+ years old, suffering from DSM-5 AUD (n = 693), and seeking outpatient treatment. MEASUREMENTS: WHO drinking risk levels, prior to treatment and at all follow-up points up to 1 year after treatment start, were assessed with Form 90. Outcomes at follow-up included consequences of drinking (Drinker Inventory of Consequences), quality of life (WHOQOL-BREF), and DSM-5 AUD symptoms (Mini International Neuropsychiatric Interview). Logistic regression and linear mixed models were used to examine the probability of maintaining risk-level reductions at follow-up and the association between risk-level reductions and outcomes, respectively. RESULTS: Reductions in risk levels were maintained over time (at least 1 level: OR 5.39, 95% CI 3.43, 8.47; at least 2 levels: OR 9.30, 95% CI 6.14, 14.07). Reductions were associated with reduced consequences of drinking and number of AUD symptoms, and minor, but statistically significant, improvements in quality of life. CONCLUSIONS: Maintaining reductions in WHO risk levels appears achievable for older adults seeking treatment for AUD. The small reduction of AUD symptoms and improvement of quality of life indicates that these reductions may not be adequate as the only treatment goal.

Impact of comorbid mental disorders on outcomes of brief outpatient treatment for DSM-5 alcohol use disorder in older adults.

BACKGROUND: Relatively little is known about the prognostic value of comorbid mental disorders in alcohol use disorder (AUD) treatment for older adults (OA). AIMS: This article aimed to investigate 1) the impact of current unipolar mood and anxiety disorders in AUD treatment success in OA, 2) the timing of this putative comorbidity impact over six months, and 3) the role of treatment length in comorbidity effects. METHODS: We analyzed baseline and one-, three-, and six-month follow-up data from the international multicenter RCT "ELDERLY-Study" (baseline n = 693, median age: 64.0 years) using mixed effects regression models. In adults aged 60+ with DSM-5 AUD "ELDERLY" compared outpatient motivational enhancement therapy (MET, four sessions) with outpatient MET plus community reinforcement approach for seniors (MET & CRA-S; up to 12 sessions). Aiming for abstinence or minimal alcohol use (AU), both conditions included CBT-elements. We assessed AU with Form 90, and mental disorders with the Mini International Neuropsychiatric Interview (M.I.N.I.). RESULTS: Mood-related disorders were associated with more drinks per day at baseline and greater reductions in drinks per day at one and six months (main effect mood disorder: Coef. 2.1, 95% CI 0.6-3.6; one month interaction effect: Coef. -1.9, 95% CI -3.3- -0.5; six months interaction effect: Coef. -2.1, 95% CI -3.5 - -0.6). These results were replicated within MET & CRA-S but not within MET. CONCLUSION: Comorbid mental disorders had modest effects on short-term outpatient treatment outcomes. OA with AUD and unipolar mood-related disorders may profit from short interventions based on motivational interviewing and CBT-elements. ClinicalTrials.gov:NCT02084173.

Implementation of strength-based case management for opioid-dependent patients presenting in medical emergency departments: rationale and study design of a randomized trial.

BACKGROUND: As the USA grapples with an opioid epidemic, medical emergency departments (EDs) have become a critical setting for intervening with opioid-dependent patients. Brief interventions designed to bridge the gap from acute ED care to longer-term treatment have shown limited efficacy for this population. Strength-based case management (SBCM) has shown strong effects on treatment linkage among patients with substance use disorders in other healthcare settings. This study aimed to investigate whether SBCM is an effective model for linking opioid-dependent ED patients with addiction treatment and pharmacotherapy. Here, we describe the implementation and challenges of adapting SBCM for the ED (SBCM-ED). Study rationale, design, and baseline characteristics are also described. METHODS: This study compared the effects of SBCM-ED to screening, assessment, and referral alone (SAR) on treatment linkage, substance use, and functioning. We recruited participants from a public hospital in NYC. Working alliance between case managers and participants and the feasibility of SBCM implementation were evaluated. Baseline data from the randomized sample were analyzed for group equivalency. Outcomes analyses are forthcoming. RESULTS: Three hundred adult participants meeting DSM-IV criteria for opioid dependence were randomly assigned to either SBCM, in which they received a maximum of six case management sessions within 90 days of enrollment, or SAR, in which they received a comprehensive referral list and pamphlet outlining drug use consequences. No significant differences were found between groups at baseline on demographic or substance use characteristics. All SAR participants and 92.6% of SBCM-ED participants initiated their assigned intervention. Over half of SBCM-ED first sessions occurred in the ED on the day of enrollment. Case managers developed a strong working alliance with SBCM-ED participants after just one session. CONCLUSION: Interventions that exceed SBIRT were accepted by an opioid-dependent patient population seen in an urban medical ED. At the time of study funding, this trial was one of the first to focus specifically on this population in this challenging setting. The successful implementation of SBCM demonstrates its adaptability to the ED and may serve as a potential model for EDs seeking to adopt an intervention that overcomes the barrier between the ED encounter and more intensive treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02586896 . Registered on 27 October 2015.