The doors of precision: Reenergizing psychiatric drug development with psychedelics and open access computational tools

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Abstract

Psychedelics paired with new applications of computational tools might help bypass the imprecision of psychiatric diagnosis and connect measures of behavior to specific physiologic targets.

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What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression.

Robert Rush, Diane Warden, S Wisniewski … (2009)

The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed.

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The Rapid Rise in Investment in Psychedelics—Cart Before the Horse

Joshua Phelps, Ravi Shah, Jeffrey A Lieberman (2022)

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Is Open Access

Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences

Galen Ballentine, Samuel Friedman, Danilo Bzdok (2022)

Psychedelics probably alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6850 free-form testimonials about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to three-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Coanalyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.

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Author and article information

Journal

Title: Science Advances

Abbreviated Title: Sci. Adv.

Publisher: American Association for the Advancement of Science (AAAS)

ISSN (Electronic): 2375-2548

Publication date Created: March 18 2022

Publication date (Print): March 18 2022

Volume: 8

Issue: 11

Affiliations

[1 ]Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA.

[2 ]Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA.

[3 ]Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.

Article

DOI: 10.1126/sciadv.abp8283

SO-VID: 323436c3-bff0-4987-8a6f-bd9a54abe89f

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The doors of precision: Reenergizing psychiatric drug development with psychedelics and open access computational tools

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Computational epistasis

What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression.

The Rapid Rise in Investment in Psychedelics—Cart Before the Horse

Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences

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