Effort-related behavior may predict relapse risk after antidepressant discontinuation

Following antidepressant discontinuation, patient decisions related to “effortful behavior” were associated with prospective relapse risk, according to a study conducted in Switzerland and Germany and published in JAMA Psychiatry.

“A perception of decreased energy or increased fatigue is a core symptom of depression in the [WHO] International Classification of Diseases, and its absence has a high negative predictive value for a diagnosis of depression,” Isabel M. Berwian, MSc, of the Translational Neuromodeling Unit at University of Zurich and Swiss Federal Institute of Technology in Switzerland, and colleagues wrote. “The decision to expend effort to obtain rewards also appears to be a robust feature of depression; patients with current depression, with subsyndromal symptoms, in their first episode of depression and in remission all showed a reduced willingness to expend effort for reward.”

The researchers noted that expending effort to obtain rewards is central to behavioral activation and other psychotherapeutic interventions because decisions about effort are associated with neurotransmitters including dopamine and serotonin, as well as with antidepressants. Thus, effort-related decisions may be important in the long-term course of depression and especially in relapses after antidepressant discontinuation.

To determine whether effortful behavior to obtain rewards represents a persistent depression process following remission, predicts relapse following remission and is impacted by antidepressant discontinuation, Berwian and colleagues collected data from 66 healthy control and 123 patients in remission from major depressive disorder in response to antidepressants prior to and following discontinuation. Data were collected at a Swiss and German university setting. The researchers used relapse during the 6 months following discontinuation as the main outcome. They also collected data on choice and decision times on a task that required participants to decide how much effort to exert for various amount of reward, and they identified these mechanisms through parameters of a computational model.

They found that patients in the main subsample (n = 74) had slower decision times than controls (n = 34). This association was particularly significant for those who later relapsed after antidepressant discontinuation (n = 21) compared with those who did not relapse (n = 39). Slower decision time predicted relapse with an accuracy of 0.66, and patients invested less effort for rewards compared with healthy controls. Deviation from standard drift-diffusion models was more prominent for patients than controls according to computational modeling. Further, patients exhibited higher mean effort sensitivity than controls. Those who relapsed differed from those who did not in terms of the evidence required to make a decision for the low-effort choice. In a smaller replication sample, group differences generally did not reach significance; however, decision time prediction models from the main sample generalized to the replication sample with a validation accuracy of 0.71, the researchers noted.

“Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation,” the researchers wrote. – by Joe Gramigna

Disclosures: Berwian reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.