Rumination in patients with major depressive disorder before and after antidepressant treatment.

BACKGROUND: Rumination is a maladaptive response to distress characteristic of Major Depressive Disorder (MDD). It is unclear to what degree rumination is associated with depression severity prior to treatment and how it responds to antidepressant treatment. Therefore, we evaluated the association between rumination and depression severity in 92 untreated patients with MDD and explored the changes in rumination after initiation of antidepressant medication. METHOD: We measured rumination using the Rumination Response Scale (RRS) and depression severity with the Hamilton Depression Rating Scale (HDRS17 or HDRS6) before and after initiation of 12 weeks of antidepressant treatment. The association between RRS and pre-treatment HDRS17 was evaluated using a linear regression model. RRS at week 4, 8, and 12 across treatment response categories (remission vs. non-response) were evaluated using a mixed effect model. RESULTS: RRS was positively associated with depression severity prior to treatment at a trend level (p = 0.06). After initiation of treatment RRS decreased significantly (p < 0.0001) and remitters exhibited lower rumination compared to non-responders at week 4 (p = 0.03), 8 (p = 0.01), and 12 (p = 0.007). LIMITATIONS: The study had no placebo group. CONCLUSIONS: Although pre-treatment rumination did not significantly associate with depressive symptoms, rumination was closely connected to change in depressive symptoms. Tormented patients could be reassured that rumination symptoms may be alleviated over the course of antidepressant treatment.

Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study.

Several studies of the effects on cognition of selective serotonin reuptake inhibitors (SSRI), administered either acutely or sub-chronically in healthy volunteers, have found changes in learning and reinforcement outcomes. In contrast, to our knowledge, there have been no studies of chronic effects of escitalopram on cognition in healthy volunteers. This is important in view of its clinical use in major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). Consequently, we aimed to investigate the chronic effect of the SSRI, escitalopram, on measures of 'cold' cognition (including inhibition, cognitive flexibility, memory) and 'hot cognition' including decision-making and particularly reinforcement learning. The study, conducted at the University of Copenhagen between May 2020 and October 2021, used a double-blind placebo-controlled design with 66 healthy volunteers, semi-randomised to receive either 20 mg of escitalopram (n = 32) or placebo (n = 34), balanced for age, sex and intelligence quotient (IQ) for at least 21 days. Questionnaires, neuropsychological tests and serum escitalopram measures were taken. We analysed group differences on the cognitive measures using linear regression models as well as innovative hierarchical Bayesian modelling of the Probabilistic Reversal Learning (PRL) task. The novel and important finding was that escitalopram reduced reinforcement sensitivity compared to placebo on both the Sequential Model-Based/Model-Free task and the PRL task. We found no other significant group differences on 'cold' or 'hot' cognition. These findings demonstrate that serotonin reuptake inhibition is involved in reinforcement learning in healthy individuals. Lower reinforcement sensitivity in response to chronic SSRI administration may reflect the 'blunting' effect often reported by patients with MDD treated with SSRIs. Trial Registration: NCT04239339 .