Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

BACKGROUND: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period. METHODS: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466). FINDINGS: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline. CONCLUSIONS: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity. FUNDING: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.

Evaluating the Implementation of Integrated Mental Health Care: A Systematic Review to Guide the Development of Quality Measures.

OBJECTIVE: Although the effectiveness of integrated mental health care has been demonstrated, its implementation in real-world settings is highly variable, may not conform to evidence-based practice, and has rarely been evaluated. Quality indicators can guide improvements in integrated care implementation. However, the literature on indicators for this purpose is limited. This article reports findings from a systematic review of existing measures by which to evaluate integrated care models in primary care settings. METHODS: Bibliographic databases and gray literature sources, including academic conference proceedings, were searched to July 2014. Measures used or proposed to evaluate integrated care implementation or outcomes were extracted and critically appraised. A qualitative synthesis was conducted to generate a panel of unique measures and to group these measures into broad domains and specific dimensions of integrated care program performance. RESULTS: From 172 literature sources, 1,255 measures were extracted, which were distilled into 148 unique measures. Existing literature frequently reports integrated care program effectiveness vis-à-vis evidence-based care processes and individual clinical outcomes, as well as efficiency (cost-effectiveness) and client satisfaction. No measures of safety of care and few measures of equitability, accessibility, or timeliness of care were located, despite the known benefits of integrated care in several of these areas. CONCLUSIONS: To realize the potential for quality measurement to improve integrated care implementation, future measures will need to incorporate domains of quality that are presently unaddressed; microprocesses of care that influence effectiveness, sustainability, and transferability of models of care; and client and health care provider perspectives on meaningful measures of quality.

Mesenchymal stromal cells expressing ErbB-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by IFN-gamma and tumor necrosis factor-alpha priming.

It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-γ-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ- plus TNF-α-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α.