Reduced Stress-Sensitivity or Increased Reward Experience: The Psychological Mechanism of Response to Antidepressant Medication

Abstract

Depression has often been associated with increased negative affect reactivity to stress (Stress-Sensitivity) and reduced capacity to experience pleasure or positive affect (Reward Experience). To date, no studies have prospectively examined changes in StressSensitivity and Reward Experience following antidepressant treatment. The sample included 83 depressed patients and 22 healthy controls. A randomized controlled trial was carried out with patients receiving either imipramine or placebo for 6 weeks. At baseline and 6 weeks, patients and controls participated in an Experience Sampling procedure, prospectively measuring ecologically valid daily life appraisals of activities and mood states. The course of depression was assessed with the Hamilton Depression Rating Scale (HDRS). Multilevel linear regression analyses showed that patients had higher negative and lower positive appraisals of activities than controls. In addition, patients showed increased Stress-Sensitivity (negative affect reactivity to negatively appraised activities). Treatment with imipramine decreased Stress-Sensitivity and increased Reward Experience (positive affect reactivity to positively appraised activities). Changes in Stress-Sensitivity and Reward Experience were in part reducible to changes in the process of activity appraisal itself. However, increase in Reward Experience, but not decrease in Stress-Sensitivity, discriminated between patients who responded and those who did not, independent of changes in the process of activity appraisal itself. Response to treatment in depression may be conditional on restoration of hedonic capacity, the cerebral substrate of which requires further study in relation to antidepressant response. A search for (synergistic) antidepressant therapies specifically targeting ability to experience reward may be warranted.

Daily life stress reactivity in remitted versus non-remitted depressed individuals

“…This finding is in concordance with the study of Wichers et al (2009). Taken together, these Table 4 Multilevel estimates of daily stress (negative event, activity, and social stress) Â group (non-remitted and remitted MDD patients at follow-up and healthy controls) on positive and negative mood states (PA and NA).…”

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…These changes in brain activity revealed at least some shared neurobiological pathways for placebo responses in pain and depression in conjunction with expectation and emotion-and reward-related circuitry involvement Wernicke and Ossanna, 2010;Murray and Stoessl, 2013). These neurobiological findings are accompanied by observations that increased subjective reward experience affects treatment efficacy with antidepressive medication (Wichers et al, 2009). In addition, the expectancy of improvement is affected by the probability of receiving active antidepressant medication, which in turn seems to influence the antidepressive response (Rutherford et al, 2013).…”

An increase in joy after two weeks is more specific of later antidepressant response than a decrease in sadness

“…In support of these results, studies have shown that antidepressant use affects the processing of both positive and negative emotions (e.g. Harmer et al, 2009;Rawlings et al, 2010), and recent studies suggest that changes in positive rather than negative emotions may be important in predicting recovery from depression (Cohn et al, 2009;Wichers et al, 2009Wichers et al, , 2010. For example, recovery from depression was associated with an increase in the ability to experience reward in daily life (Wichers et al, 2009).…”