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Preparation Before Psychedelics Tied to Better MDD, With Gianluca Florineth, MSc
Greater exposure to preparation therapy before psychedelic dosing was linked to larger reductions in depressive symptoms, a new study found.
In psychedelic-assisted therapy for depression, the timing of psychotherapy may be as important as its delivery, with new evidence highlighting preparation sessions as a key driver in symptom improvement.
A recent systematic review and meta-analysis suggests that greater exposure to preparation therapy before psychedelic dosing is associated with larger reductions in depressive symptoms, whereas post-dosing integration therapy and total therapy duration show no clear relationship with short-term outcomes.
“We were also quite surprised, but there are some ways that we can explain this non-significant association,” said investigator Gianluca Florineth, MSc, from the Translational Research Center, University Hospital of Psychiatry and Psychotherapy at the University of Bern in Switzerland, in an interview with HCPLive. “We definitely do not want to encourage people to stop doing integration sessions because we also believe that it's very important. However, the role may not be as much in reducing the depressive symptoms, but in, for example, maintaining them long-term, or in helping participants reduce potential follow-up effects from the substances.”
The analysis pooled data from 12 controlled clinical trials involving 733 adults (49.8% females; mean age, 42.1 years) who received psilocybin- or LSD-assisted therapy for depressive symptoms. Across studies, investigators examined associations between depressive symptom change and several therapy-related variables, including hours of preparation therapy, integration therapy, total psychotherapy exposure, and overall treatment duration.
Each additional hour of preparation therapy correlated with greater symptom reduction (P = .04), while integration hours (P = .53) and total therapy time (P = .86) were not significantly associated with outcomes. Florineth suggested that integration therapy may address functions not captured by short-term depression scales, such as helping patients process challenging material, consolidate insights, and sustain benefits over time.
The study also found that longer follow-up periods were associated with smaller effect sizes, consistent with an attenuation of treatment effects over time (P = .003). Most studies (75%) had a high risk of bias, often due to ineffective blinding.
Additionally, Florineth emphasized that preparation therapy may play a critical role in shaping the acute psychedelic experience by establishing psychological safety, aligning expectations, and strengthening the therapeutic alliance before dosing. These factors may reduce the risk of distressing or destabilizing experiences during psychedelic sessions and support more favorable clinical outcomes.
When asked which element of preparation therapy most strongly drives symptom reduction, Florineth cited a combination of factors.
“The most important is that participants or patients have a sense of safety, because if you have very short preparation periods before the substance sessions, you may not really feel comfortable with the facilitators that are present,” Florineth said. “This general therapeutic alliance building is probably most important.”
Florineth has no relevant disclosures.
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