Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints. METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function. RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures. LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin. CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

Depressive symptoms and spiritual wellbeing in asymptomatic heart failure patients.

Depression adversely predicts prognosis in individuals with symptomatic heart failure. In some clinical populations, spiritual wellness is considered to be a protective factor against depressive symptoms. This study examined associations among depressive symptoms, spiritual wellbeing, sleep, fatigue, functional capacity, and inflammatory biomarkers in 132 men and women with asymptomatic stage B heart failure (age 66.5 years ± 10.5). Approximately 32 % of the patients scored ≥10 on the Beck Depression Inventory, indicating potentially clinically relevant depressive symptoms. Multiple regression analysis predicting fewer depressive symptoms included the following significant variables: a lower inflammatory score comprised of disease-relevant biomarkers (p < 0.02), less fatigue (p < 0.001), better sleep (p < 0.04), and more spiritual wellbeing (p < 0.01) (overall model F = 26.6, p < 0.001, adjusted R square = 0.629). Further analyses indicated that the meaning (p < 0.01) and peace (p < 0.01) subscales, but not the faith (p = 0.332) subscale, of spiritual wellbeing were independently associated with fewer depressive symptoms. Interventions aimed at increasing spiritual wellbeing in patients lives, and specifically meaning and peace, may be a potential treatment target for depressive symptoms asymptomatic heart failure.

Listening to depression and suicide risk in medical students: the Healer Education Assessment and Referral (HEAR) Program.

OBJECTIVE: A growing body of literature documents high rates of burnout, depression, and suicidal ideation among physicians and medical students. Barriers to seeking mental health treatment in this group include concerns about time, stigma, confidentiality, and potential career impact. The authors describe a 4-year trial of the Healer Education Assessment and Referral (HEAR) program, designed to increase mental health services utilization (MHSU) and decrease suicide risk (SR) as assessed by an Interactive Screening Program (ISP)at one US medical school. METHODS: Over a 4-year period, medical students were engaged in face-to-face, campus-wide, educational group programs and were invited to complete an individual, online, and anonymous survey. This survey contained the 9-item Patient Health Questionnaire (PHQ-9) scale to assess depression and items to identify suicidal thoughts and behaviors, substance use, distressing emotional states, and the use of mental health treatment. Students who engaged in this ISP by corresponding electronically with a counselor after completing the survey were assessed and when indicated, referred to further treatment. RESULTS: The HEAR program was delivered to 1,008 medical students. Thirty-four percent (343/1,008) completed the online screening portion. Almost 8 % of respondents met the criteria for high/significant SR upon analysis of the completed screens. Ten out of 13 of the students with SR who dialogued with a counselor were not already receiving mental health treatment, indicating that this anonymous ISP identified a high proportion of an untreated, at risk, and potentially suicidal population. MHSU among medical students who completed the survey was 11.5 % in year 1 and 15.0 % by year 4. SR among medical students was 8.8 % in year 1 and 6.2 % in year 4 as assessed by the ISP. CONCLUSIONS: This novel interventional program identified at risk, potentially suicidal medical students at one institution. Based on this single-site experience, we suggest that future multisite studies incorporate a comparison group, acquire baseline (prematriculation) data regarding MHSU and SR, and use an individualized yet anonymous identification system to measure changes in individual participants' mental health status over time.

Pain in depression: STAR*D study findings.

BACKGROUND: Pain complaints commonly accompany major depressive disorder (MDD). However, whether patients with MDD and pain complaints differ from those without pain complaints is not well studied. OBJECTIVE: The objective of this study was to compare depressed outpatients with and those without current pain complaints in terms of sociodemographic, clinical, and presenting symptom features. METHODS: The baseline clinical and sociodemographic data of a large representative outpatient sample with nonpsychotic MDD (n=3745) enrolled in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study were collected. Baseline information on pain complaints was based on Item No. 25 (somatic pain) of the 30-item Inventory of Depressive Symptomatology-Clinician Rating (IDS-C(30)). RESULTS: After adjusting for sex, depression severity (IDS-C(30) less Item No. 25), and general medical comorbidities (as measured by the Cumulative Illness Rating Scale total score), we found clinically meaningful differences between patients with and those without pain complaints. Younger, African American, Hispanic, and less educated patients were more likely to report pain complaints. In addition, those with pain complaints were more likely to report anxious features with irritable mood, sympathetic nervous system arousal, and gastrointestinal problems as well as poorer quality of life. Neither a more chronic course of illness nor suicidal ideation was associated with pain. CONCLUSIONS: Pain complaints are common among outpatients with MDD and are associated with certain symptom features and poorer quality of life. However, the findings of this study suggest that depression accompanied by pain complaints does not increase the clinical psychiatric burden or chronicity of depression.

Clinical and demographic features of atypical depression in outpatients with major depressive disorder: preliminary findings from STAR*D.

OBJECTIVE: To determine the frequency and demographic and clinical characteristics of depression with atypical features in a broadly representative sample of outpatients. METHOD: Data derived from the first 1500 patients with DSM-IV major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression trial at 41 primary care and nonresearch psychiatric outpatient clinics. An algorithm based on the 30-item Inventory of Depressive Symptomatology-Clinician Rating (IDS-C30) determined presence or absence of depression with atypical features. Odds ratios determined whether a variety of demographic and clinical parameters differed between patients meeting and not meeting atypical criteria. RESULTS: Over 18% of the sample met criteria for atypical features based on items from the IDS-C30. The atypical group was more likely to be female and have an earlier age at onset, greater comorbidity with anxiety symptoms, and greater symptom severity compared with the nonatypical group. CONCLUSION: Previously identified features of atypical depression were confirmed in this large and broadly representative, nonresearch clinical population.