Results of esketamine administration in a Greek population; A case series

Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.