More effective than results suggest?
Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.
Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said
“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.
Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.
Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.
Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”
Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”
The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.
A version of this article first appeared on Medscape.com.