Anhedonia, the reduced ability to experience pleasure, is a core symptom of both unipolar and bipolar depression that often responds poorly to standard antidepressants. In a real-world observational study of 253 treatment-resistant patients (199 with unipolar depression, 54 with bipolar depression), repeated doses of esketamine nasal spray added to ongoing medication significantly reduced anhedonia over three months. The effect was distinct from overall mood improvement. At three months, 51.92% of bipolar and 38% of unipolar patients showed at least a 50% reduction in anhedonia scores. Dropout rates were low (around 13–14%), and manic switches were rare. The findings suggest esketamine has a targeted, transdiagnostic anti-anhedonic effect.
Intranasal esketamine substantially reduced depression severity in 210 patients with treatment-resistant depression treated in routine clinical practice. Depression scores improved markedly over three months, and men showed a modest advantage over women by the end of treatment, with lower depression ratings and higher rates of response and remission. Among patients under 65 years, sex differences were small and not statistically significant; among those 65 and older, men appeared to benefit more numerically, but this difference did not hold up after statistical correction and remains uncertain. Discontinuation rates and safety outcomes were similar between sexes. The authors call for future studies to examine hormonal, vascular, inflammatory, and other factors that might explain the observed sex differences.