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Amygdala reactivity, antidepressant discontinuation and relapse: a longitudinal, observational study with a randomized component

Importance: Antidepressant discontinuation substantially increases the risk of a depression relapse.
The neurobiological mechanisms through which this happens are not known. Amygdala reactivity
to negative information is a marker of negative affective processes in depression that is reduced by
antidepressant medication. However, it is unknown whether amygdala reactivity is sensitive to antide-
pressant discontinuation, and whether any change is related to the risk of relapse after antidepressant
discontinuation.

Objective: To investigate whether amygdala reactivity to negative facial emotions changes with
antidepressant discontinuation and relates to subsequent relapse.

Design: The AIDA study was a longitudinal, observational AIDA study, where patients were random-
ized to task-based fMRI measurement of amygdala reactivity either twice before, or after discontinuing
antidepressants. Relapse was monitored over a six month follow-up period. Study recruitment took
place until January 2018. Data were collected between July 1, 2015, to January 31, 2019 and statistical
analyses were conducted between June 2021 and December 2023.

Setting: University setting in Zurich, Switzerland, and Berlin, Germany.

Participants: Patients with remitted major depressive disorder (rMDD) on antidepressants. Of 123
recruited patients, 80 (mean (SD) age 35.5 (11.4) years; 60
women (75%) were included in analyses.
Of 66 recruited healthy controls matched for age, sex, and education, 53 were included in analyses
(mean (SD) age 34.9 (10.7) years); 37 women (70%)).

Exposure: Discontinuation of antidepressant medication.

Outcomes: Task-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months
after discontinuation. Results: Amygdala reactivity of rMDD patients on medication did not differ from controls (left: t = 0.77)

Tore Erdmann, Isabel M. Berwian, Klaas Enno Stephan, Erich Seifritz, Henrik Walter and Quentin J. M. Huys

The full paper can be found here.

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