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 via OpenAlex
Summary
AI-generated from the abstractNine antidepressant compounds with mechanisms beyond the monoaminergic hypothesis have shown positive results in phase II or III trials. AXS-05 (dextromethorphan and bupropion) and ansofaxine hydrochloride outperformed placebo in phase III trials for major depressive disorder or treatment-resistant depression. MIJ821, nitrous oxide, psilocybin, ayahuasca, botulinum toxin A facial injection, prasterone, and casopitant each showed at least one positive phase II result. Ayahuasca produced a greater response rate than placebo at one week, suggesting rapid antidepressant effects. These novel compounds may expand treatment options if preliminary findings are confirmed.
Study at a glance
| 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 |
| Citations | 35 |
| Key finding | 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.