Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder.

BACKGROUND: Depression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder. METHODS: This phase 2, open-label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25-mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist-to-patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability. RESULTS: Thirty participants completed the study. No psilocybin-related serious adverse events occurred; treatment-related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to -16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks. CONCLUSIONS: Psilocybin-assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group-oriented format, compact delivery time, community cancer center setting, and one-to-one therapist-to-patient ratio could also add to therapeutic gains and efficiency of administration. TRIAL REGISTRATION: NCT04593563. PLAIN LANGUAGE SUMMARY: Depression is common in patients with cancer and associated with lower treatment adherence, reduced quality of life, and limited response to antidepressants and psychotherapy. We conducted a phase 2 trial to study a single dose of psilocybin administered in a group therapy setting with one-to-one therapist-to-participant psychological support to patients with curable and noncurable cancer and major depressive disorder. Findings of the study showed safety (no treatment-related serious adverse events or suicidality) with psilocybin and suggested efficacy, with a significant reduction in depression severity scores from baseline to posttreatment. Further investigation is warranted.

Developing a Direct Observation Measure of Therapeutic Connection in Psilocybin-Assisted Therapy: A Feasibility Study.

Context: Measuring therapeutic connection during psilocybin-assisted therapy is essential to understand underlying mechanisms, inform training, and guide quality improvement. Purpose: To evaluate the feasibility of directly observing indicators of therapeutic connection during psilocybin administration encounters. Methods: We evaluated audio and video data from a recent clinical trial for observable expressions of therapeutic connection as defined in proposed best-practice competencies (i.e., empathic abiding presence and interpersonal grounding). We selected the first four 8-hour encounters involving unique participants, therapists, and gender pairs. Each video was independently coded by three members of an interprofessional six-person team. Using a structured checklist, coders recorded start-stop times, the audible (i.e., speech prosody or words) and visible (i.e., body movements, eye gaze, and touch) cues marking the event, and the qualities of the interaction (e.g., expression of awe, trust, distress, and calmness). We assessed feasibility by observing the frequency, distribution, and overlap of cues and qualities coders used to identify and define moments of therapeutic connection. Results: Among the 2074 minutes of video, coders recorded 372 moments of therapeutic connection. Eighty-three percent were identified by at least two coders and 41% by all three. Coders used a combination of audible and visual cues to identify therapeutic connection in 51% of observed events (190/372). Both the cues and qualities of therapeutic connection expressions varied over the course of psilocybin temporal effects on states of consciousness. Conclusion: Direct observation of therapeutic human connection is feasible, sensitive to changes in states of consciousness and requires evaluation of audible and visual data.