Based on the study results, investigators concluded that there is justification for a randomized clinical trial.
Use of psilocybin therapy could improve symptoms of major depressive disorder in patients with cancer, according to new study findings published in JAMA Oncology. Approximately 15% of patients with cancer experience major depression, and research has linked this with lower treatment adherence and reduced quality of life. Despite this, oncologists often feel ill-equipped to address mental health issues, and many treatment options have proven to be ineffective for depression.
Psilocybin, a 5-HT2A receptor agonist, may offer a new option. According to investigators, psilocybin has successfully reduced a variety of psychiatric symptoms in studies with 2 therapists per patient. In the new study, investigators aimed to create a scalable, rapidly effective treatment for depression with psilocybin in a 1-to-1 therapist-to-patient ratio. Investigators also noted that to their knowledge, this study marks the first psilocybin therapy trial conducted in a community cancer setting rather than a psychiatric hospital or academic center.
“The study was novel in that it used a group approach, as well as was done in a Community Cancer Center. So all the previous studies using psychedelic assisted therapy in cancer patients were done in specialized academic hospitals or large psychiatric [facilities],” said lead investigator Manish Agrawal, MD, faculty at the Center for Psychedelic Therapy and Research, co-director of Clinical Research at Aquilino Cancer Center, and co-founder and CEO of Sunstone Therapies, during an interview with Pharmacy Times®.
In the phase 2, single-center, fixed-dose, open-label study, 30 participants were recruited at Aquilino Cancer Center or were referred from specialized psychiatric and oncology services. Patients were grouped into cohorts of 3 to 4 based on timing of recruitment. All participants were adults with a cancer diagnosis and major depression disorder.
The mean age of participants was 56 years, with 30% men and 70% women. Fourteen (47%) of the participants had curable cancers, whereas 16 (53%) had non-curable cancers. Additionally, 50% had reported previous therapy with antidepressant drugs.
Each cohort was simultaneously treated with a 25-mg dose of COMP360 in adjacent rooms open to a common space, with a 1-to-1 therapist-to-patient ratio. The cohorts received group therapy in 1 preparation and 2 integration sessions, supplemented by individual therapy. Outcomes included safety and improvement in depression, as measured primarily by the Montgomery-Asberg Depression Rating Scale (MADRS). Higher scores denoted greater severity of depression.
“[Patients] would come in and have a group preparation, and then get psilocybin at the same time and in rooms that were adjacent to each other. So we call that simultaneous administration,” Agrawal said. “The next day, [the patients] come back and talk about their experience, and then again a week later [they] talk about their experience—[that’s] called integration. So that has not yet been done in [patients with cancer], or really any population where there was a simultaneous administration, group prep, and group integration all at the same time.”
Sustained response to treatment was defined as a decrease in MADRS score of 50% or more from baseline to week 3 and week 8, and remission was defined as a MADRS score lower than 10 after treatment. Other measures of depression included the Quick Inventory of Depressive Symptomatology–Self-Report and the Maudsley Visual Analogue Scale.
No treatment-related serious adverse events (AEs) occurred in the study and there was no suicidality based on the Columbia Suicide Severity Rating Scale. AEs were mild or expected, including headache (n=24), nausea (n=12), altered mood (n=8), anxiety (n=7), and hallucinations (n=1).
Notably, efficacy of the psilocybin treatment was suggested based on the robust reduction in MADRS scores from baseline to post-treatment. According to the results, investigators saw a reduction of 19.1 points by week 8, and a sustained response was observed in 80% of patients. Importantly, 15 (50%) of patients showed full remission of depressive symptoms.
“Eighty percent of the participants had more than 50% reduction in their depression symptoms based on the MADRS and 50% had a complete remission, that is their MADRS score came down to the same level as someone that did not have depression,” Agrawal said.
The MADRS score findings were further supported by self-reported measures of depressive symptoms. Quick Inventory of Depressive Symptomatology–Self-Report scores declined by an average of 5.9 points, or a 48% reduction from baseline to week 8. The Maudsley Visual Analogue Scale also showed a reduction by 46.2 points, a 53% decrease in self-rated depression severity.
Based on these findings, the investigators said participants experienced clinically meaningful, rapid, and sustained improvement in symptoms of depression over 8 weeks following a single treatment with psilocybin therapy, including patients with both curable and incurable cancers.
The investigators did note several limitations, including the lack of control arm. Further research is needed to compare placebo and other antidepressant treatments for patients with cancer, but the researchers concluded that their findings justify a randomized clinical trial.
“It's quite a small study at 30 patients, so it has limitations, [such as] there was no placebo arm. But still, the efficacy was quite interesting and profound,” Agrawal said. “But even more exciting was people really found a connection in the group and wanted to find a benefit speaking about their experience and their story together. Even though the trials are completed and people followed up for 8 weeks, people continue to meet once a month now, 2 years later, because of the benefits they found in the trials, [which] showed quite remarkable results.”
Agrawal M, Emanuel E, Richards B, Richards W, Roddy K, Thambi P. Assessment of Psilocybin Therapy for Patients With Cancer and Major Depressive Disorder. JAMA Oncology. April 13, 2023. Accessed April 13, 2023. doi:10.1001/jamaoncol.2023.0351