Esketamine is a novel antidepressant approved by the FDA in 2019 in the form of an intranasal spray, recommended for Treatment-Resistant Depression (TRD). The intranasal spray system appears to be more manageable than intravenous ketamine infusion. It contains ketamine’s S- isomer which is four-fold more potent for the NMDA receptor.

The aim of this case series is to describe our clinical experience in the use of Esketamine.

6 TRD patients (3 men; 3 women) were recruited in San Raffaele Turro Hospital from March 2021. All patients (2 bipolar and 4 unipolar) were diagnosed with a Major Depressive Episode according to DSM-5 criteria, resistant to at least two antidepressants. Initially, Esketamine was administrated twice weekly for one month; afterward, it was administrated once weekly for a month; finally, it was administrated once weekly or every two weeks for a month. Clinical scales (HAM-D, YMRS, SSI, HAM-A, MADRS, CADSS) were administrated to assess symptoms and sides effects before and after each administration on a weekly basis.

Three patients out of six showed an improvement in depressive symptoms: two patients had remission (final HAM-D score < 8); one patient had a clinical response (final HAM-D score < 50 % respect baseline value). Three patients withdrew the treatment: two for perceived inefficacy, after 16 and 19 administrations, one for personal reasons.

The use of Esketamine in our TRD patients showed good effectiveness and tolerability but randomized controlled clinical trials are needed to confirm our findings.

No significant relationships.