Psychological Medicine

Original Articles

Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms

R. Uhera1 c1, R. H. Perlisa2, N. Henigsberga3, A. Zobela4, M. Rietschela5, O. Morsa6, J. Hausera7, M. Z. Dernovseka8, D. Souerya9, M. Bajsa3, W. Maiera4, K. J. Aitchisona1, A. Farmera1 and P. McGuffina1

a1 MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK

a2 Center for Experimental Drugs and Diagnostics, Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Boston, USA

a3 Croatian Institute for Brain Research, Medical School, University of Zagreb, Croatia

a4 Department of Psychiatry, University of Bonn, Germany

a5 Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Mannheim, Germany

a6 Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

a7 Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poland

a8 University Psychiatric Clinic, Ljubljana, Slovenia

a9 Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel – Centre Européen de Psychologie Médicale, Belgium


Background Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.

Method We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D).

Results The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates.

Conclusions Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.

(Received July 07 2011)

(Revised August 12 2011)

(Accepted August 23 2011)

(Online publication September 20 2011)


c1 Address for correspondence: Dr R. Uher, P080, SGDP, Institute of Psychiatry, 16 De Crespigny Park, London SE5 8AF, UK. (Email: