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W48

EARLY MOTIVATIONAL AND HEDONIC RESPONSES TO ANTIDEPRESSANTS IN MAJOR DEPRESSIVE DISORDER: A REAL-WORLD EVIDENCE STUDY

Maurice M. Ohayon — Stéphanie Duhoux2, Maggie McCue3, Michael Martin3, Priscilla Driscoll Shempp3, Andrew Krystal4, Marie-Lise Côté5 1Stanford Sleep Epidemiology Research Center, Stanford University School of Medicine, 2Eval Research Institute, 3Takeda Pharmaceuticals U.S.A., Inc., 4University of California San Francisco, 5Centre d’Évaluation et de Statistiques

2026 ASCP Annual Meeting

Background

Loss of interest or pleasure is a hallmark of major depressive disorder (MDD) and typically eases before other depressive symptoms once treatment is initiated.1, 2 This study examined changes in depressive and anhedonic symptoms in adults with MDD receiving commonly prescribed antidepressants (ADs), focusing on early rebound of motivation and age‑related variations in response patterns.

Methods

Adults with MDD and receiving AD therapy participated in online interviews using the Ad-Infer EVAL system, a tool designed for positive and differential AI diagnosis assessment and data collection. Wave 1 (W1) ran from May 2024 to October 2024. Wave 2 (W2) spanned September 2024 to March 2025, achieving a follow‑up rate of 56.4%. In the adjusted sample, participants were assigned to 1 of 3 medication groups: fluoxetine or paroxetine (GR1, n=75), bupropion (GR2, n=44), or vortioxetine (GR3, n=40); they were then stratified into 3 age groups ( < 35, 35-54, and ≥55 years [y]). Differences in proportions of MDD prevalence, depressive symptoms, or anhedonic symptoms were compared between 2 timepoints within groups with McNemar test or between groups with Bonferroni-corrected chi-square test.

Results

Most participants were female (GR1, 81.0%; GR2, 54.5%; GR3, 77.5%);19% were aged < 35 y, 51% were between 35-54 y, and 30% were aged ≥55 y. By W2, MDD prevalence dropped by 14% in GR1, 30.1% in GR2 and 20% in GR3. Relapse was markedly higher in GR1 (87%) than in GR2 (50%) or GR3 (51%; P < .01). Across treatment groups, participants showed significant improvement in motivation (GR2, P=.003; GR3, P=.05), social satisfaction (GR1, P < .001; GR3, P=.001), and cognitive functioning (GR1, P=.0045; GR2, P=.005; GR3, P=.05); similar improvements were observed for each medication group across the 3 age subgroups. GR3 experienced a rise in motivation for the participants aged < 35 and 35-54 y, with gains hovering between 23.6% (P=.002) and 13.6%, respectively. Both GR2 and GR3 exhibited reductions in anhedonia, shifting from 77.8% to 38.8% (P < .001) and from 60.9% to 44.4% (P=.030), respectively. While the reduction was significant for younger and middle-aged adults for GR1, a reduction in anhedonia was observed in GR3 only among adults aged ≥55 y, with prevalence decreasing from 42.9% to 15.4% (P=.0004). Significant improvements in cognitive function were observed across treatment groups ranging from 17.5% (GR3, P=.05) to 30.4% (GR2, P=.005) gains. A noteworthy dip in psychomotor retardation was observed, especially within the GR1 and GR2 cohorts: from 64.8% to 41.5% in GR1 (P=.004) and from 43.2% to 9.8% in GR2 (P < .001).

Conclusion

Results of this real‑world study suggest that early response in motivation symptoms and anhedonia is a frequent phenomenon in AD treatment arguing for the clinical usefulness of being an early predictor symptom in MDD. Different response profiles were seen by medication class, where bupropion and vortioxetine exhibited lower relapse rates and more reductions in anhedonia compared with SSRIs. There was some age-related variation in responses; younger and middle-aged adults may have experienced particularly selective benefits of vortioxetine, whereas older adults may have had the strongest anhedonia reduction. Collectively, these findings underscore the clinical importance of monitoring motivational and anhedonic symptoms during early treatment and suggest that AD strategies should be based on symptom profiles rather than solely on depression severity.