title: [Approximate entropy of the placebo effect in clinical trials of newer antidepressants].
abstract: Recent research concluded that antidepressant drugs are ineffective in treating moderate or severe depression. Statistically, there are no differences between the results with active drugs or placebo. Some authors have attributed this fail to variability or irregularity of the placebo effect in depressed patients or artifacts induced by meta-analysis. This fact highlights the difficulties faced by the research of psychoactive drugs in depression and revives the debate about the usefulness of the employ of placebo in these studies. This study aimed to determine the variability of the placebo effect in antidepressant clinical trials in simple linear and non-linear complex models. We performed a secondary analysis of data from 35 trials presented as evidence to the Food and Drug Administration (FDA) for approval of new generation antidepressants, all double-blind controlled with placebo in patients with unipolar mild or moderate depressive disorder, according to the criteria of "Diagnostic and Statistical Manual of Mental Disorders (DSM).Articles reviewed included 5133 patients . We have calculated the coefficient of variability, autocorrelation and approximate entropy of the placebo and treatment effects to determine whether the variability or regularity between different studies should be attributed to meta-analytical methods, placebo effect or ineffective treatment itself. The coefficient of variability in the placebo group was 26.49% and 18.81% in the treatment group. The placebo effect autocorrelation was within the confidential limits while the treatment group was outside showed cyclical variation. The approximate entropy value (ApEn N=35,m=2,R=2) in the placebo group was 0.5579 and 0.5744 in treatment group, leading to the conclusion that placebo effect is highly consistent and regular in complex non-linear models. The apparent variability of the placebo effect in depressed patients should be due to artifacts induced by simple linear models analysis.
authors.affiliation: Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba.
authors.forename: Maria Eloisa
authors.initials: ME
authors.lastname: Cuestas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cuestas
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003511:Cyclohexanols / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D017374:Paroxetine / Q000627:therapeutic use*; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use; D012720:Severity of Illness Index; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D010919:Placebos; D005473:Fluoxetine; D017374:Paroxetine; D000069470:Venlafaxine Hydrochloride