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Psychological medicine · 2025

Which aspects of anhedonia predict response to pharmacotherapy in major depressive disorder?

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Uher Rudolf, Rizvi Sakina J, Quilty Lena C, Pavlova Barbara, Nunes Abraham, Foster Jane A, Lam Raymond W, Milev Roumen, Müller Daniel J, Taylor Valerie, Soares Claudio N, Rotzinger Susan, Kennedy Sidney H, Frey Benicio N

Аннотация

BACKGROUND: Anhedonia is a multidimensional concept, and it is not known which aspects of it are linked to the heterogeneity of treatment responses in major depressive disorder (MDD). We examine the role of anhedonia dimensions in predicting response to antidepressant medication and adjunctive pharmacotherapy.

METHODS: In CAN-BIND-1, 187 adults with MDD completed the Dimensional Anhedonia Rating Scale (DARS) and the Snaith-Hamilton Pleasure Scale (SHAPS) before undergoing 8 weeks of treatment with escitalopram. At week 8, 90 nonresponders received adjunctive treatment with aripiprazole for an additional 8 weeks. Mixed-effects models tested the hobbies, food, social, and sensory subscales and items of DARS and SHAPS as predictors of change in the Montgomery-Åsberg Depression Rating Scale (MADRS).

RESULTS: Of the four DARS subscales, sensory anhedonia predicted a worse treatment outcome with escitalopram (b = 1.14, 95%CI 0.08 to 2.20, p = 0.034) as did a three-item SHAPS sensory anhedonia subscale (b = 1.50, 95%CI 0.43 to 2.57, p = 0.006). A combined DARS-SHAPS sensory anhedonia subscale complemented the previously reported interest-activity symptom dimension to improve treatment outcome prediction. In contrast, food and social anhedonia dimensions predicted worse outcomes with adjunctive aripiprazole (b = 2.52, 95%CI 1.25 to 3.80, p < 0.001; b = 2.56, 95%CI 1.16 to 3.96, p < 0.001). Corresponding SHAPS items showed similar results.

CONCLUSIONS: The inability to enjoy sensory experiences and the lack of interest in food and social activities distinctly predict outcomes with serotonergic versus dopaminergic pharmacotherapy. These findings require replication and extension to other treatments.

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