Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial
Aaronson, S. T., LaPratt, J., Lauterbach, M., Miller, T., Sackeim, H. A., Shoultz, A., Suppes, T., Swartz, K., van der Vaart, A.
This open-label trial (n=12) conducted at Sheppard Pratt Hospital finds that psilocybin (25mg) significantly decreases depressive symptoms in patients with severe treatment-resistant depression (TRD) at 3 weeks (MADRS −15.8) and 12 weeks (MADRS −17.2) post-treatment. Exploratory analyses suggest the Oceanic Boundlessness dimension correlates with antidepressant responses, while patients with comorbid PTSD show reduced antidepressant effects.
Abstract
Objective: Depression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD.Methods: This was a 12-week, open-label trial conducted at Sheppard Pratt Hospital. Participants were 18-65 years of age, in a major depressive episode with documented insufficient benefit from at least five treatments during the current episode. A single dose of synthetic psilocybin (25 mg) was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing through at least 3 weeks post-dosing. Therapists met with patients for three sessions during pretreatment, during the 8-hour dosing day, and for three integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures including MADRS scores up to 12 weeks posttreatment, and subject-rated scales capturing depression and level of function were completed at baseline and all subsequent visits.Results: Twelve participants (six male, six female; mean age=40.6 years [SD=9.6]) with severe TRD were followed over the study period. Depressive symptoms were significantly decreased at week 3 (MADRS least-squares mean change=−15.8, 95% CI=−25.4 to −6.3) and Week 12 (MADRS least-squares mean change=−17.2, 95% CI=−25.2 to −9.1). In exploratory analyses, the Oceanic Boundlessness (OB) dimension of the psychedelic experience correlated with post-dosing antidepressant responses. Patients with comorbid PTSD (N=5) showed significantly less antidepressant effect of psilocybin.Conclusions: This open-label study suggests efficacy and safety of psilocybin in severe TRD and supports further study of psychedelics in this population, including consideration of PTSD interaction effects.