Depression: High doses of psilocybin can be as effective as escilatopram

Antipsychotics are psychoactive substances that tend to treat various mental illnesses such as depression and post-traumatic stress disorder (PTSD). Common examples of psychedelics are psilocybin, LSD, and MDMA.

Although psychotropic drugs have shown promise in the treatment of depression, conducting blinded studies can be challenging due to the subjective effects of psychotropic drugs. Thus, there may be different placebo effects and possible biases.

The researchers of this review wanted to compare the monotherapy use of psychotropic drugs with escitalopram, a common drug used to treat depression. To help overcome some of the problems with reduced placebo effects in psychotropic drug trials, the authors were careful to distinguish between placebo responses in psychotropic trials and placebo responses in antidepressant trials.

This review and Bayesian network meta-analysis included randomized controlled trials in adult participants with clinically diagnosed depression.

For all data, they focused on changes in depressive symptoms as the primary outcome. In total, they were able to contribute data from 19 studies: 811 participants in antipsychotic trials and 1968 participants in escitalopram trials.

Based on their synthesis of the data, the researchers found that the placebo effect in the antipsychotic trials was smaller than the placebo effect in the escitalopram trials.

Compared to the placebo results of the escitalopram studies, high-dose psilocybin was slightly more effective. Researchers typically defined high doses of psilocybin as 20 mg or more. In addition, a high dose of psilocybin was also slightly more effective than escitalopram.

David Merrill, MD, PhD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, California, and the Singleton Endowed Chair in Integrative Brain Health, who was not involved in the study, noted the following about the review’s findings:

“This study used meta-analysis methods to compare the effectiveness of antipsychotics and escitalopram (Lexapro) on depressive symptoms. Interestingly, only high doses of psilocybin showed greater efficacy than escitalopram. High-dose psilocybin shows promise as a fast-acting, short-term treatment for depression. This is compared to antidepressants, which take weeks, if not months, to kick in and only continue to work with continued use,” he said. Medical news today.

“Although not addressed in this study, there is clinical consensus that the benefits of high-dose psilocybin can last for months and possibly years after an acute treatment session. Sometimes even just one treatment session is needed for otherwise chronic, incurable depression. This is part of why assisted psychotherapy under safe, controlled professional conditions is gathering such momentum and enthusiasm in the fields of psychology and psychiatry,” he added.

This review has limitations. First, it is necessary to acknowledge that all studies included in the review had limitations. For example, researchers acknowledge that the effects of psychotropic drugs may be overestimated compared to placebo in an internal study, which is why researchers chose to look at how psychotropic drugs compare to placebo antidepressants and low-dose psychotropic drugs. They also acknowledge that participants who received psilocybin often also received psychotherapy or psychological support, which may have influenced the results.

The researchers also focused on acute effects, so future studies need to evaluate the long-term effects of all related drugs.

The researchers chose to include a broad range of depression types and included studies with participants who had terminal illnesses or life-threatening diagnoses and depressive symptoms as well as participants with PTSD. Most participants in MDMA trials had PTSD, while most participants in escitalopram trials had major depressive disorder (MDD). Since the two conditions are different, the results do not necessarily translate. The review also included only a handful of experiments.

The researchers were also limited by choosing to compare with a very low-dose psychoactive drug, which is not a true placebo. The results may also have been affected by the conflict of direct and indirect evidence and direct evidence bias, which may have overestimated the effects of high-dose psilocybin compared with other treatments.

The inclusion and exclusion parameters also limited the researchers, so future studies may include different variables and inclusion criteria.

Finally, the researchers acknowledge that their meta-analysis may not have sufficient statistical power to identify publication bias. Researchers also acknowledge that “Most of the evidence for treatment comparisons was moderate or low.”

Standardization in psychotropic medication

The study’s authors suggest that improving blinding methods and having more standardized psychotherapies could help increase understanding of the effectiveness of psychotropic drugs.

Matthew W. Johnson, PhD, director of the Sheppard Pratt Center of Excellence for Psilocybin Research and Treatment, who was not involved in the study, was skeptical of the review’s findings, noting the following: Today’s medical news:

“The main reason I don’t trust this particular method is that the various studies were too different, including the population studied and the disorders treated (existential distress, MDD, PTSD), to directly compare them in that way . .”

“When performing pooled analyses, such as the meta-analysis or network analysis performed here, it is important to make sure that pooled studies are similar enough to each other to make sense.” Otherwise, such methods can lead one to think they are getting a valid answer, but you are actually basing it on an apples-to-oranges comparison,” he explained.

Despite the limitations of this review, the findings potentially point to expanding treatment options for people with depression. This allows doctors and people with depression to choose from more treatments to find what works for the individual.

Based on this study, high-dose psilocybin appeared to be similar to the effects of antidepressants in the treatment of major depression. Thus, the researchers recommended that psilocybin should probably be used alongside psychological support.

“These findings give hope to those suffering from depression – especially those who find antidepressants ineffective or intolerable because of side effects.” While there are always potential risks to using drugs to treat health conditions, this review shows that with the right mindset and treatment setting, high-dose psychotropic medications can be used safely and effectively to treat depression, with results on par or better than observed with antidepressant drugs.”
— David Merrill, MD, Ph.D

“Many in the field are working diligently to build a renewed evidence base to allow for the validation and regulatory approval of psilocybin and other psychotropic treatments for depression, PTSD, addiction, and other health conditions,” Merrill said.