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Trajectories of change in depression severity during treatment with antidepressants

Authors :
Katherine J. Aitchison
Neven Henigsberg
Astrid Zobel
Marcella Rietschel
J. Jaracz
Bengt Muthén
Peter McGuffin
Ana Petrovic
Daniel Souery
Anna Placentino
Rudolf Uher
Anne Farmer
Ole Mors
Source :
Uher, R, Muthén, B, Souery, D, Mors, O, Jaracz, J, Placentino, A, Petrovic, A, Zobel, A, Henigsberg, N, Rietschel, M, Aitchison, K J, Farmer, A & McGuffin, P 2009, ' Trajectories of change in depression severity during treatment with antidepressants ', Psychological Medicine, pp. 1-11 . https://doi.org/10.1017/S0033291709991528
Publication Year :
2010

Abstract

BackgroundResponse and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change.MethodGrowth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses.ResultsThe final two-piece growth mixture model categorized participants into a majority (75%) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results.ConclusionsLatent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

Details

Language :
English
ISSN :
00332917
Database :
OpenAIRE
Journal :
Uher, R, Muthén, B, Souery, D, Mors, O, Jaracz, J, Placentino, A, Petrovic, A, Zobel, A, Henigsberg, N, Rietschel, M, Aitchison, K J, Farmer, A & McGuffin, P 2009, ' Trajectories of change in depression severity during treatment with antidepressants ', Psychological Medicine, pp. 1-11 . https://doi.org/10.1017/S0033291709991528
Accession number :
edsair.doi.dedup.....35f97c0c3fb9055bf5fb3bded00034a0
Full Text :
https://doi.org/10.1017/s0033291709991528