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Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry

Hitoshi Sakurai, Kengo Yonezawa, Hideaki Tani, Masaru Mimura, Michael Bauer, Hiroyuki Uchida

Pharmacopsychiatry January 19, 2022 DOI: 10.1055/a-1714-9097 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Interventions AXS-05 ansofaxine hydrochloride MIJ821 nitrous oxide psilocybin ayahuasca facial injection of botulinum toxin A prasterone casopitant
Topics Anxiety Depression Psilocybin
Keywords Placebo Antidepressant Clinical trial Depression economics Pharmacology Hallucinogen Alternative medicine
Citations 35
Key findings Nine antidepressant compounds with novel mechanisms of action demonstrated positive results over placebo in phase II or III trials for depression.

Abstract

Abstract Introduction There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis.

Methods: We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of phase II and III trials were identified. The collateral information was gathered via a PubMed search and press releases.

Results: Nine compounds were identified. AXS-05 (a combination of dextromethorphan and bupropion) and ansofaxine hydrochloride showed a positive result over placebo in a phase III study for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, facial injection of botulinum toxin A, prasterone, and casopitant demonstrated at least one positive result in phase II trials. Ayahuasca showed a greater response rate than placebo at week one, indicating the rapid antidepressant effect.

Discussion: These new compounds with novel mechanisms of action are expected to provide a greater variety of treatment options for depression if preliminary positive results are confirmed.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for anxiety, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials 2016 Systematic review
The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression 2020 Meta-analysis n = 117
Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews Patients with mood, anxiety, or substance-use disorders, including cancer patients and... 2018 Systematic review of systematic reviews
A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy 2020 Systematic review

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