Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms
Open accessAbstract
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.
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Anhedonia and impaired reward circuit pathways are associated with a poorer prognosis and suboptimal treatment response.
“Anhedonia and impaired reward circuit pathways are associated with a poorer prognosis and suboptimal treatment response (Buckner et al., 2008;Uher et al., 2012;Treadway and Zald, 2011).”
From Effectiveness of Vortioxetine on Emotional Blunting in Patients with Major Depressive Disorder with inadequate response to SSRI/SNRI treatment (2021) · cites this paper as Uher et al., 2012
The Discussion (page not provided) reports that depressed patients with prominent loss of interest and reduced activity improved less during antidepressant treatment and were less likely to achieve remission. This supports the treatment-response part of the claim, but the paper does not establish an association between impaired reward circuit pathways and prognosis or treatment response. (LLM, conf=0.87)
Experimental — accuracy not yet measuredReduction of the interest-activity dimension predicts poor outcome in depressed patients undergoing antidepressant treatment, found in 811 MDD patients and replicated in 3737 MDD patients from STAR*D.
“This result was found in a large cohort of 811 patients with major depressive disorder (MDD) and consecutively replicated in a regression analysis in a larger population of 3737 MDD patients derived from the STAR*D trial within the same publication (Uher et al., 2012).”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Uher et al., 2012
PVS reductions predict acute symptom severity, poor treatment response, and a chronic, relapsing future course in depression.
“Whilst it has long been recognised that NVS elevations are prognostically important in depression, it is now increasingly acknowledged that PVS reductions also predict acute symptom severity, poor treatment response, and a chronic, relapsing future course (Spijker, Bijl, De Graaf, & Nolen, 2001;Uher et al., 2012, McMakin et al., 2012; see reviews by Dunn & Roberts, 2016;Dunn, in press).”
From Bringing light into darkness: A multiple baseline mixed methods case series evaluation of Augmented Depression Therapy (ADepT) (2019) · cites this paper as Uher et al., 2012
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- Authors
- Uher, R., Perlis, R. H., Henigsberg, N., Zobel, A., Rietschel, M., Mors, O., Hauser, J., Dernovsek, M. Z., Souery, D., Bajs, M., Maier, W., Aitchison, K. J., Farmer, A., & McGuffin, P.
- Affiliations
- King's College London (GB)
- Massachusetts General Hospital (US)
- University of Zagreb (HR)
- University of Bonn (DE)
- Central Institute of Mental Health (DE)
- Aarhus University Hospital (DK)
- Poznan University of Medical Sciences (PL)
- Université Libre de Bruxelles (BE)
- Corresponding author
- Uher, R.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2011-09-20
- Volume
- 42
- Issue
- 5
- Pages
- 967-980
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC3787526
- OpenAlex
- W2034528843
- Cited by
- 420
- References
- 59
- Citations by year
- 2026: 30 · 2025: 42 · 2024: 47 · 2023: 33 · 2022: 31 · 2021: 35 · 2020: 44 · 2019: 33 · 2018: 32 · 2017: 24 · 2016: 24 · 2015: 13 · 2014: 16 · 2013: 7 · 2012: 9
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- GlaxoSmithKline
- National Institute for Health and Care Research
- European Commission
- H. Lundbeck A/S
- National Institutes of Health (n01mh90003-26-0-0)
- National Institute of Mental Health (N01 MH090003, MH-086026, R01MH086026)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- major depressive disorder, antidepressant treatment outcome, loss of interest, reduced activity, indecision, escitalopram, nortriptyline, citalopram, STAR*D, predictors of treatment response
- MeSH terms
- Activities of Daily Living, Adult, Affect, Antidepressive Agents, Tricyclic, Cognition, Depressive Disorder, Major, Major Depressive Disorder, Europe, Factor Analysis, Statistical, Female, Humans, Male, Nortriptyline, Predictive Value of Tests, Psychiatric Status Rating Scales, Severity of Illness Index, Reproducibility of Results, Citalopram, Treatment Outcome, Antidepressive Agents, Second-Generation
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