Emotional Blunting in SSRI-Treated Patients vs. Preserved Affective Responsiveness with Esketamine in Treatment-Resistant Depression: A Comparative Study and Review

Introduction:: Emotional blunting—i.e., a subjective reduction in emotional range and intensity—is frequently reported during SSRI treatment and may hinder full functional recovery in major depressive disorder (MDD). Esketamine, a rapid-acting glutamatergic antidepressant approved for treatment-resistant depression (TRD), may exert antidepressant benefits while preserving emotional responsiveness. Methods:: We conducted a two-arm, naturalistic observational study including 60 adults with TRD (SSRI monotherapy, n=30; adjunctive intranasal esketamine, n=30). Emotional blunting and emotional intensity were assessed at baseline and week 4 using the Oxford Depression Questionnaire (ODQ), the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA), the Laukes Emotional Intensity Scale (LEIS), and the Self-Assessment Manikin (SAM). Depressive symptoms were measured with the Montgomery–Åsberg Depression Rating Scale (MADRS). Between- group comparisons used independent-samples t-tests with effect-size estimation. Results:: Both groups improved in depressive symptoms, with a significantly greater MADRS reduction in the esketamine group (−16.7 vs −5.4 points; p< 0.0001). Compared with esketamine, SSRI-treated patients reported higher emotional blunting (ODQ and OQESA; p< 0.0001) and lower emotional intensity/valence (LEIS and SAM; p< 0.0001). Discussion:: Adjunctive esketamine was associated with both superior antidepressant improvement and a more preserved emotional experience than SSRI monotherapy. Conclusion:: In TRD, adjunctive intranasal esketamine was associated with reduced emotional blunting and greater symptom improvement versus SSRI monotherapy, supporting routine assessment of emotional side effects in treatment planning.