Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts. DATA SYNTHESIS AND STUDY QUALITY: Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges' g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies' sample sizes. Study quality was appraised using Cochrane's Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines. ELIGIBILITY CRITERIA: Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible. RESULTS: Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges' g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges' g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating. CONCLUSION: Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023388065.

Acceptability, Engagement, and Exploratory Outcomes of an Emotional Well-being App: Mixed Methods Preliminary Evaluation and Descriptive Analysis.

BACKGROUND: There is growing evidence suggesting that the emotional well-being of the public has been negatively affected in the past year. Consequently, demand for well-being support has increased. Although there is substantial empirical support for mental health apps that target diagnosed conditions, there is less research on emotional well-being apps. Among existing well-being apps, few studies have been conducted on apps that are based on lived experience and those that seek to enhance users' understanding of their emotional patterns. Thus, the acceptability of these novel apps requires further evaluation before upscaling. OBJECTIVE: This evaluation aims to describe the acceptability, engagement, and preliminary outcomes of using an app (Paradym) designed to promote emotional well-being and positive mental health. METHODS: This is a pre-post, mixed-methods, single-arm evaluation that is aggregated with digital analytics data. We anonymously collected real-world data on the demographics and well-being of the participants as well as the usability and acceptance of the app using validated questionnaires and open-ended questions. Participants tested the app for a minimum of 2 weeks before completing the follow-up measures. Google Analytics was used to record the level of app engagement. Chi-square and 2-tailed t tests were conducted to analyze quantitative data, and a thematic analysis approach was adopted for qualitative data. RESULTS: A total of 115 participants completed baseline questionnaires, of which 79.1% (91/115) users downloaded the app. The sample was diverse in terms of ethnicity, including 43.4% (50/115) people who self-identified as belonging to minority ethnic groups. Most of the participants were female (78/115, 67.8%) and between the ages of 18 and 25 years (39/115, 33.9%). A total of 34 app users who completed questionnaires at baseline and follow-up provided valuable feedback to inform the future directions of Paradym. Favorable themes emerged describing the app's content, functionality, and underlying principles. Although usability feedback varied across items, a considerable number of participants (22/34, 64%) found that the app was easy to use. Google Analytics revealed that at least 79% (27/34) of people used the app daily. On the basis of preliminary observations, app users experience increased mental well-being. Post hoc analyses indicated that the reduction in depression scores (t33=-2.16) and the increase in the well-being measures (t33=2.87) were statistically significant. No adverse events were reported during the follow-up period. CONCLUSIONS: The findings of this evaluation are encouraging and document positive preliminary evidence for the Paradym app.