Under Pressure: Stronger depressive symptoms are associated with more positive expectations towards experimental treatments

Background: Despite significant advancements in the treatment of depression, challenges such as inadequate response rates and high placebo effects highlight the need for improved therapies and a deeper understanding of treatment expectations. Patient expectations play a crucial role in treatment outcomes but have not been systematically investigated in the context of novel interventions like ketamine and psilocybin. Objectives: This study aimed to assess patient acceptance, experiences, and expectations regarding established depression treatments (psychotherapy, psychotherapy plus antidepressants) and novel interventions (ketamine-assisted therapy, psilocybin-assisted therapy, psychotherapy plus placebo). Methods: A web-based survey (N = 404) was conducted using a case vignette depicting a patient diagnosed with severe depression. Participants rated treatment acceptance, ranked treatment preferences, and reported expectations regarding improvement, worsening, and side effects for each intervention. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9). Repeated-measures analyses of variance (RM-ANOVA) and multilevel modeling were used to examine the relationship between treatment expectations and depression severity. Results: Established treatments were more accepted and preferred over novel interventions, with psychotherapy receiving the highest acceptance (98.3%) and psilocybin the lowest (47.5%). Participants expected greater symptom improvement from traditional treatments compared to ketamine and psilocybin, which were associated with higher expectations of worsening and side effects. However, higher depression severity was linked to more favorable expectations of ketamine- and psilocybin-assisted therapy. This effect was specific to novel treatments and was not observed for psychotherapy or antidepressants. Conclusions: Traditional depression treatments are viewed as more acceptable and effective, while novel interventions evoke skepticism, likely due to unfamiliarity and concerns about risks. However, individuals with more severe depressive symptoms exhibit greater openness to innovative treatments. These findings underline the importance of managing patient expectations in psychedelic-assisted therapy and suggest that clinician education and well-balanced informed consent procedures could improve treatment acceptance.