Early score fluctuation and placebo response in a study of major depressive disorder

• Published in: Journal of psychiatric research 2020-02, Vol.121, p.118-125
• Main Authors: Targum, Steven D., Cameron, Beth R., Ferreira, Ludvina, MacDonald, I. David
• Format: Article
• Language: English
• Subjects: Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Augmentation treatment; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - physiopathology; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Humans; Major depressive disorder; Outcome Assessment, Health Care - standards; Placebo Effect; Placebo response; Post-hoc analyses; Psychiatric Status Rating Scales; Remission Induction; Reproducibility of Results; Research Design; S-adenosylmethionine; S-Adenosylmethionine - administration & dosage; S-Adenosylmethionine - pharmacology; Score fluctuation
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2019.11.014

Early score fluctuation in double-blind, placebo-controlled studies may affect the reliability of the baseline measurement and adversely affect the eventual study outcome. We examined the effect of early score fluctuation during a 2-week double-blind placebo lead-in period in a phase II, double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects who had had an inadequate response to ongoing antidepressant treatment. The overall study failed to meet its specified endpoints. We examined the score trajectories of all placebo-assigned subjects during the double-blind placebo lead-in period and subsequent 6-week treatment period. Placebo-assigned subjects with ≥20% HamD17 or MADRS score fluctuations (improvement or worsening) during the double-blind placebo lead-in period (prior to randomization) had significantly higher rates of placebo response and remission at week 8 compared to subjects with