A six-month follow-up study of a Phase 2 clinical trial investigating psilocybin versus escitalopram for the treatment of major depressive disorder has shown positive results.

Around 30% of people living with depression in the UK are resistant to current treatments, highlighting an urgent need for new therapies. As the researchers of this study highlight, even for patients who have had their depression successfully treated, there is a high risk of relapse, with one in three patients relapsing within the year.

Equally, SSRI treatments often include side effects such as sexual dysfunction, weight gain, fatigue, and emotional blunting.

The authors note that a key consideration of any treatment of major depressive disorder “is its capacity to produce sustained antidepressant response or remission.”

Mounting evidence is increasingly pointing to psilocybin-assisted therapy as an innovative new treatment for the condition, with clinical trials showing that the therapy is capable of producing rapid and long-lasting antidepressant effects.

However, while clinical trials have investigated the treatment itself, they have not compared the treatment to the current gold standard in depression medications or looked at the long-term effects of the treatment.

This Phase 2 trial is the first to compare the long-term antidepressant effects of these two treatments alongside mental health measures including work and social functioning, connectedness, and meaning in life. 

In the trial, patients with major depressive disorder recruited from a UK hospital were administered either two doses of 25mg of psilocybin along with psychological support, or a six-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram in combination with psychological support.

The findings, published in eClinicalMedicine, revealed that both administered treatments saw sustained improvements in depressive symptoms, however, patients who were administered psilocybin-assisted psychotherapy saw greater lasting improvements. 

These improvements included psychosocial functioning, meaning in life, and psychological connectedness.

Dr James Rucker, Consultant Psychiatrist & Senior Clinical Lecturer in Psychopharmacology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said: “The authors have tended to attribute differences observed in this study to comparative differences between the drugs themselves, however, it is also possible that the results reflect biased reporting between groups. 

“This is more likely here because A) studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and B) study participants were unblinded during the long-term follow-up phase that is reported in the paper, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. 

“The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe and the US.”

The authors write: “Key limitations of the study include its suboptimal power to detect small but meaningful differences between treatments, missing data, the potential use of additional interventions during the follow-up period, and reliance on self-reported treatment assessments. 

“These factors may affect the interpretation of the study findings and should be considered when evaluating the results.”

With these considerations in mind, the researchers suggest that the findings warrant further investigation into psilocybin-assisted psychotherapy for the treatment of depression.

Shortwave Life Sciences has announced it has achieved a significant breakthrough in its ambitions to transform eating disorder care with positive pre-clinical results from its latest pharmacodynamics study, demonstrating the safety of its psilocybin-based drug combination for the treatment of anorexia nervosa.

Anorexia nervosa has one of the highest fatality rates. The condition is a complex mental health condition as well as a metabolic disease, yet no FDA-approved pharmacological treatments are currently available for the condition.

Shortwave Life Sciences in collaboration with Science in Action, an expert pre-clinical GLP-certified lab in Israel, has now tested the safety of buccal administration of Shortwave’s combination drug comprised of psilocybin and a beta-carboline.

The company says this novel treatment provides an expanded mechanism of action and a therapeutic effect superior to psilocybin alone, impacting more than one group of receptors in the brain.

For the study, three groups of rats were given varying doses of the combination drug (0.23ml, 0.5ml, and 1ml), with results showing no adverse effects, weight changes, or behavioural changes following the psychedelic effects.

“This is a monumental step forward for Shortwave. Our relentless pursuit of breakthrough mental health treatments comes with the responsibility of ensuring safety at every stage,” commented Shortwave Life Sciences CEO Rivki Stern Youdkevich.

“We are proud of the positive outcomes from this rigorous pre-clinical trial, further validating our patent-pending drug combination and buccal delivery system.

“With this success, we are reaffirmed in our approach to addressing the global mental health crisis.”

In the pre-clinical pharmacodynamics study, all subjects remained healthy and unaffected during the trial, which Shortwave has stated marks a strong foundation for future clinical development.

Furthermore, no adverse events or vital sign changes were reported across all groups, and the results confirmed the safety profile for the psilocybin-based combination drug at elevated doses.

This achievement comes on the heels of the International PCT Examining Committee’s recent acknowledgment of Shortwave’s patent claims for its novel, non-obvious, and industrially applicable mucoadhesive buccal film.

Designed for rapid absorption and bypassing liver and gut degradation, the platform holds transformative potential for patients facing metabolic and psychiatric challenges. This method of administration is designed to be sensitive to patient needs, who may not want to swallow the medicine, and also provides higher bioavailability.

A first-of-its-kind study has revealed that millions of Americans could benefit from psilocybin therapy if approved by the U.S. Food and Drug Administration.

With 14.8 million people in the US living with Major Depressive Disorder, 2.7 million of these patients meet the criteria for Treatment Resistant Depression. Equally, with limited to no innovation in mental health treatment for decades, this number highlights a desperate need for new therapies. Psychedelics have shown incredible promise in emerging research as such treatments.

While the FDA recently delivered a huge blow to both patients and industry with the rejection of MDMA-assisted psychotherapy for the treatment of PTSD, the organisation is set to consider the approval of psilocybin for the treatment of depression later this year.

This latest study, carried out by Emory University, the University of Wisconsin-Madison, and UC Berkeley, determined that up to 62% of patients currently receiving treatment for depression could qualify for psilocybin therapy if approved.

“Our findings suggest that if the FDA gives the green light, psilocybin-assisted therapy has the potential to help millions of Americans who suffer from depression” said Syed Fayzan Rab, an Emory MD candidate and the study’s lead author, in a press statement.

“This underscores the importance of understanding the practical realities of rolling out this novel treatment on a large scale.”

Understanding the scale of need

The researchers evaluated the population of 9 million Americans receiving treatment for depression against various eligibility criteria used in recent clinical trials of psilocybin for depression.

The team then came up with estimates to see who would be eligible for psilocybin-assisted psychotherapy.

The first “lower-bound” range estimated that 24% of patients would be eligible if the strict criteria of initial trials were applied.

The “mid-range” estimated that 56% would be eligible based on criteria likely to be used in real-world medical settings, and an “upper-bound” range estimated that 62% would be eligible after accounting for patients with multiple exclusionary conditions.

However, the researchers emphasised that the 62% upper-bound estimate is likely a conservative one, as the analysis focused only on currently treated individuals and did not account for the potential influx of new patients drawn by the appeal of psychedelic medicine.

Equally, they emphasise that these projections depend on FDA approval parameters and real-world implementation factors such as insurance coverage decisions and the availability of trained practitioners.

“While our analysis is a crucial first step, we’ve only scratched the surface in understanding the true public health impact psilocybin therapy may have,” said Dr. Charles Raison, in a press statement. Dr. Raison is a collaborator on the study and the lead investigator on one of the largest clinical trials looking at the efficacy of psilocybin therapy for depression.

“Ultimately, the realisable potential of this treatment rests in the hands of regulatory bodies, policymakers, insurers, and the healthcare community at large.

“It’s our hope that these findings spur productive discussions and proactive preparations to optimize the benefit to patients while minimising unintended consequences.”