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Psychedelics Expand Options, Not Efficacy, in Depression Care, With Balázs Szigeti, PhD
Findings suggest psychedelics match antidepressants for symptom relief, with future research needed on real-world use and functional outcomes.
As interest in psychedelic-assisted therapy (PAT) continues to grow, new data suggest its role in depression treatment may be more complementary than transformative.
In an interview with HCPLive, Balázs Szigeti, PhD, from the Translational Psychedelic Research Program at the University of California, San Francisco (UCSF), discussed how clinicians should interpret recent findings showing no significant difference in core depressive symptom improvement between PAT and traditional antidepressants under comparable unblinding conditions.
Rather than positioning PAT as a replacement for existing therapies, Szigeti framed it as an additional tool in the treatment armamentarium. Differences in adverse event profiles, treatment logistics, and patient preferences will likely shape its clinical role.
“It's just one more tool that the clinician can use to treat their patients,” he said.
In the meta-analysis of 24 studies, PAT and open-label antidepressants brought comparable reductions in depression scores, with an estimated difference of 0.3 points on the Hamilton Depression Rating Scale (HAM-D) (95% confidence interval [CI], −1.39 to 1.98; P =.73). These findings challenge earlier beliefs that psychedelics may provide substantially greater efficacy than standard antidepressants, which had fueled enthusiasm in the psychiatry field.
According to Szigeti, the study also adds methodological clarity to a debate increasingly shaped by concerns over trial design, particularly functional unblinding. Earlier trials on MDMA-assisted therapy for PTSD largely overlooked this issue, but scrutiny intensified following the US Food & Drug Administration (FDA) decision. Szigeti noted that his team’s meta-analytic approach offers a way to address these biases without relying on elusive “active placebo” controls.
Beyond symptom reduction, Szigeti highlighted the need to expand how treatment success is measured. Functional outcomes, such as quality of life, daily functioning, and overall well-being, remain underrepresented in antidepressant trials.
“Psychedelic studies started to collect such data because, from anecdotal evidence, there are indications that psychedelics improve in those domains as well,” Szigeti said. “The issue is that, because they are not there with the traditional antidepressant trial[s], we just have no basis of comparison.”
Szigeti identified the gap between clinical trials and real-world use as a critical challenge. Antidepressant studies often assess outcomes at 8 weeks, despite long-term use in practice. He expects this disconnect to be even more pronounced with psychedelics, given the added psychotherapy component.
“It always struck me as something weird that we are putting millions and billions of dollars into clinical research, but very often how these medicines are used in real life has nothing to do with how we have tested them in clinical research,” Szigeti said. “The real question is how the efficacy is going to look once it is practiced in real life, not in the highly constrained clinical research environment.”
Szigeti has no reported disclosures.
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