Psilocybin may bring greater long-term depression symptom relief than SSRIs

For this study, researchers recruited 59 adults with a diagnosis of moderate-to-severe depression. Thirty participants received two 25-milligram doses of psilocybin, while the remaining 29 followed a 6-week course of an SSRI called escitalopram.

Participants also received about 20 hours of psychological support.

At the study’s conclusion, researchers found that both groups showed notable improvement in their depression symptoms, even up to the 6-month follow-up.

“[Psilocybin] disrupts the persistent ruminative loops of negative thinking that underpins depression,” David Nutt, DM, FRCP, FRCPsych, FMedSci, DLaws, the Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences at Imperial College London and one of the authors of this study, told Medical News Today.

“We did show that remission rates were much higher for psilocybin than for escitalopram even though the mean scores for depression reductions were not different,” he added.

“The reasons for this are complex and likely due to high variability of some scores and the fact that after the two month treatment trial, we did not control what the patients took in terms of medicines, i.e. they could seek out other treatments,” Nutt explained.

Additionally, in the psilocybin group, participants also reported significant advancement in social functioning and psychological connectedness during the 6-month follow-up.

“This is important because improving connectedness and having greater meaning in life can significantly enhance a person’s quality of life and long-term mental health,” David Erritzoe, MD, PhD, MRCPsych, clinical director and deputy head of the Centre for Psychedelic Research at Imperial College London and co-first author of the study stated in a press release.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression, addressing both the symptoms of depression and overall well-being. This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment,” Erritzoe advised.

As to Nutt, he also pointed out that:

“This further supports the view that psilocybin works quite differently to escitalopram, especially that it doesn’t suppress emotions like escitalopram does. Just 2 psilocybin doses are at least as effective at treating depression as 6 weeks treatment with escitalopram with better remission rates and improved well-being outcomes up to 6 months.”

“We will be reporting outcomes of psilocybin treatment in anorexia, OCD [obsessive-compulsive disorder], and fibromyalgia next year,” he told us. “Our current research is exploring if just a single dose of psilocybin can help treat addictions to heroin and gambling.”

After reviewing this study, Simon B. Goldberg, PhD, Kellner Family Distinguished Chair in Education and Well-Being and associate professor in the Department of Counseling Psychology and Core Faculty at the Center for Healthy Minds at the University of Wisconsin – Madison, who was not involved in the research, told MNT that he thought it was very exciting that work investigating alternatives to antidepressants is showing these kinds of promising results.

“Depression is extremely common and burdensome, so there is a huge public health need for effective treatments,” Goldberg explained. “It was quite intriguing that the psychedelic condition was showing benefits above and beyond escitalopram on some measures of well-being.”

“Although antidepressants are helpful for many people, they have some important limitations,” he continued. “Many patients do not respond to them, they can have substantial side effects, and benefits may not persist when someone stops taking the antidepressant. There is some evidence that there also may be withdrawal symptoms associated with discontinuing antidepressants.”

MNT also spoke with David Merrill, MD, PhD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health, about this study.

“The mind-altering and intensive nature of psychedelics makes it such that comparing the two is nice in theory but the access barriers for one treatment versus the other remain significant,” Merrill, who was also not involved in the research, pointed out.

“It will take some doing before the comparable effectiveness matches the realistic opportunity for patients to access the two treatments equally,” he added.

Merrill said it is important for researchers to continue to look for alternatives to standard SSRIs as it helps us understand mechanisms of depression.

“There may be ways to achieve the benefits of psychedelics without the drugs,” he noted. “For example, through holotropic breathing. But even that can be of an intensity such that it’s recommended to be tried only under direct supervision of an experienced practitioner.”

Matthew W. Johnson, PhD, senior investigator at the Sheppard Pratt Center of Excellence for Psilocybin Research and Treatment in Baltimore, MD — who reviewed this study for MNT — pointed out that psilocybin has not been approved for depression by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), or similar regulatory bodies.

“Therefore it is important to move toward and complete phase 3 trials to potentially garner that approval,” Johnson continued. “Such larger studies are also better able to study the risks of psilocybin, which is something I have researched over the years.“

“Larger studies are better equipped to identify relatively uncommon adverse effects. We need to know how prevalent such effects are under clinical conditions and optimize screening and treatment methods to minimize harm,” Johnson explained.

Finally, MNT also spoke with Rachel Yehuda, PhD, Endowed Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and director of The Parsons Research Center for Psychedelic Healing at Mount Sinai, who commented this is an important study showing that the long term effects of both psilocybin and escitalopram are durable six months after treatment.

“This is the kind of information that the field needs in order to understand long-term impacts of psychedelic therapies,” Yehuda, who was not involved in this research, explained.

“What I really liked about this study is that we are finally starting to talk about outcome measures beyond symptom severity, which in mental health, can be extremely informative. Many people with symptoms can tolerate them better if they can live lives full of meaning, connectedness, and social functioning. Simply measuring severity of depression or other mental health conditions often does [not] give the full picture of well-being,” she told us.

“That said, the study also calls for more long-term follow up of psychedelic therapies as there is a suggestion in the data, particularly in the supplementary tables, that the magnitude of the symptom severity differences are reduced over time in the psilocybin group compared to the escitalopram group. Again, if overall people feel like their lives have improved, this argues for a more diverse set of primary outcomes in evaluating the efficacy and long-term benefits of any mental health treatment.”

– Rachel Yehuda, PhD