In adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant leads to higher remission rates than quetiapine extended-release combined with an oral antidepressant. Starting at week 8, 28.3% of esketamine-treated patients achieved remission compared to 18.6% on quetiapine, and by week 32, 55.7% versus 36.3%. Depressive symptoms improved more with esketamine from day 8 onward. Fewer patients stopped treatment due to side effects with esketamine (4.5%) than with quetiapine (10.1%). These results come from a secondary analysis of a randomized trial.
In adults with treatment-resistant depression, adding esketamine nasal spray to a newly initiated oral antidepressant led to greater improvement in depressive symptoms than oral antidepressant plus placebo spray. Across two short-term trials, the group receiving esketamine plus oral antidepressant showed a mean reduction of 12.8 points on the Patient Health Questionnaire-9 (PHQ-9) at 28 days, compared with 10.3 points in the placebo group, a statistically significant difference. 77.1% of patients in the esketamine group achieved a clinically meaningful improvement (at least a 6-point drop) versus 64% in the placebo group. In a separate relapse-prevention study, 57.3% of patients on esketamine plus oral antidepressant maintained remission (PHQ-9 score ≤4) versus 44.2% on oral antidepressant plus placebo. The self-reported PHQ-9 results aligned with clinician-rated Montgomery-Åsberg Depression Rating Scale scores.