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One in three patients relapse after antidepressant discontinuation within six months, and there is little guidance for clinicians or patients on how and when discontinuation is safe. Identification of relapse predictors hence constitutes an urgent clinical problem.
In a longitudinal randomized observational prognostic two-site study (AIDA), remitted patients on antidepressants were assessed using a broad battery of clinical interviews, questionnaires, neuroimaging and behavioral tasks before antidepressant discontinuation, and followed up for six months to assess relapse. Half of the sample was assessed a second time after discontinuation, half twice before discontinuation. For the examined variables, we computed the balanced accuracy of correctly classifying patients as relapsers or non-relapsers out-of-sample.
123 patients were included of which 30 finished the study with a relapse and 52 without. Here, we report the results from four analyses. 1) Clinical and demographic variables did not predict subsequent relapse better than chance. 2) However, EEG-alpha asymmetry during a sad mood induction predicted relapse with a balanced accuracy of 0.7. 3) Furthermore, patients invested less for reward in a physical effort task and subsequent relapsers took longer to decide which option to choose. The development and application of a generative computational model for this decision-making process based on value-based and drift-diffusion models allowed us to identify that the former result is due to increasJed effort sensitivity in patients and the later to a higher boundary in relapsers. The higher decision times predicted relapse in the main (0.66) and in a validation sample (0.71). 4) Resting-state functional connectivity did not predict relapse prior to discontinuation, but connectivity between the dorsolateral prefrontal cortex and the parietal cortex changed due to discontinuation and predicted relapse with a balanced accuracy of 0.86 in patients who were also assessed after discontinuation.
In summary, several markers of relapse after antidepressant discontinuation might, if confirmed in larger replication studies, be useful in a clinical setting.
Postdoctoral Researcher
Nivlab
Princeton Neuroscience Institute
Princeton University