Changing the paradigm in treatment-resistant depression: A review of long-term efficacy and tolerability of esketamine nasal spray.

Treatment-resistant depression (TRD) is a major public health problem worldwide. There are currently five strategies for its treatment: optimization, change, combination, augmentation, and somatic therapies. However, many of these therapies are not fully effective, are not accessible, or have a significant number of side effects. Esketamine nasal spray has recently been approved, in combination with another oral antidepressant, for TRD, with excellent results in short-term studies. We consider in this review whether this therapy is also safe and effective in the long-term treatment of patients. A narrative review, using a comprehensive Pubmed search, and other search strategies, of long-term studies evaluating the safety and efficacy of esketamine nasal spray for the treatment of TRD has been conducted. Five studies have been included in the review. Esketamine nasal spray has demonstrated long-term efficacy and safety in both placebo-controlled and open-label studies evaluating maintenance of antidepressant response. In addition, one study has reported a high level of patient satisfaction with treatment. As limitations, a systematic search for studies has not been carried out and these are still scarce, given the short time that has elapsed since the discovery of the molecule. Esketamine nasal spray is the greatest pharmacological novelty in the treatment of major depression in the last 50 years. It constitutes a new paradigm in the treatment of TRD, which should make us rethink the care protocols that we currently follow. However, more studies are still needed to consolidate the data found so far. (PsycInfo Database Record (c) 2023 APA, all rights reserved).