Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry
Pharmacopsychiatry – January 19, 2022
Source: OpenAlex
Summary
Ayahuasca demonstrated a rapid antidepressant effect in a clinical trial, showing a greater response rate than placebo within one week. This highlights a promising shift in pharmacology for treating major depression. Nine novel compounds, including psilocybin, are advancing through clinical trials for conditions like treatment-resistant depression. These new medicines, emerging from psychedelics and drug studies, offer hope for psychiatry by moving beyond traditional neurotransmitter receptor influence on behavior, providing diverse options for effective depression treatment.
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.