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Original Investigation
February 19, 2020

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation

Author Affiliations
  • 1Translational Neuromodeling Unit, University of Zurich and Swiss Federal Institute of Technology in Zurich, Zurich, Switzerland
  • 2Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
  • 3Charité Universitätsmedizin, Campus Charité Mitte, Berlin, Germany
  • 4Department of Psychology, University of California, Berkeley
  • 5Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom
  • 6Max Planck Institute for Metabolism Research, Cologne, Germany
  • 7Division of Psychiatry, University College London, London, United Kingdom
  • 8Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom
JAMA Psychiatry. Published online February 19, 2020. doi:10.1001/jamapsychiatry.2019.4971
Key Points

Question  Do decisions about trading effort for reward differentiate patients whose depression is in remission and who are still taking medication from controls, and are these decisions associated with relapse after stopping medication?

Findings  This prognostic study found that patients whose depression was in remission but who still took medication were more sensitive to effort. These patients took longer to make these decisions, which was predictive of the risk of relapse after stopping antidepressants.

Meaning  Even when their depression is in remission, patients taking antidepressant medications show characteristic differences in how they trade rewards for effort, and these differences might be a clinically useful predictor of relapse if medication is discontinued.


Importance  Nearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario.

Objectives  To establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation.

Design, Setting, and Participants  This longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018.

Exposure  Discontinuation of antidepressants.

Main Outcomes and Measures  Relapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model.

Results  A total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n = 74) compared with controls (n = 34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d = 0.52; P = .02), particularly for those who later relapsed after discontinuation of antidepressants (n = 21) compared with those who did not relapse (n = 39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d = 0.77; P < .001). This slower decision time predicted relapse (accuracy = 0.66; P = .007). Patients invested less effort than healthy controls for rewards (F1,98 = 33.970; P < .001). Computational modeling identified a mean (SD) deviation from standard drift-diffusion models that was more prominent for patients than controls (patients, 0.67 [1.56]; controls, –0.71 [1.93]; Cohen d = 0.82; P < .001). Patients also showed higher mean (SD) effort sensitivity than controls (patients, 0.31 [0.92]; controls, –0.08 [1.03]; Cohen d = 0.51; P = .05). Relapsers differed from nonrelapsers in terms of the evidence required to make a decision for the low-effort choice (mean [SD]: relapsers, 1.36 [0.35]; nonrelapsers, 1.17 [0.26]; Cohen d = 0.65; P = .02). Group differences generally did not reach significance in the smaller replication sample (27 patients and 21 controls), but decision time prediction models from the main sample generalized to the replication sample (validation accuracy = 0.71; P = .03).

Conclusions and Relevance  This study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.

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