1. Early score fluctuation and placebo response in a study of major depressive disorder
- Author
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Beth R. Cameron, Ludvina Ferreira, I. David MacDonald, and Steven D. Targum
- Subjects
S-Adenosylmethionine ,medicine.medical_specialty ,Randomization ,Affect (psychology) ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Biological Psychiatry ,Psychiatric Status Rating Scales ,Depressive Disorder, Major ,Placebo response ,business.industry ,Clinical study design ,Remission Induction ,Reproducibility of Results ,Drug Synergism ,Placebo Effect ,medicine.disease ,Antidepressive Agents ,Treatment period ,030227 psychiatry ,Psychiatry and Mental health ,Research Design ,Major depressive disorder ,Antidepressant ,Drug Therapy, Combination ,business ,030217 neurology & neurosurgery - Abstract
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 A reliable baseline measure is an asset for signal detection. These post-hoc findings suggest that study designs that anticipate and attempt to manage early response prior to randomization may yield more meaningful outcome data for trials of MDD and possibly other disorders as well.
- Published
- 2020
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