Treatment-resistant depression and intranasal esketamine: Spanish consensus on theoretical aspects

Summary

Treatment-resistant depression (TRD) occurs when a patient fails to respond to at least two adequate antidepressant trials, and it imposes a greater social and economic burden than non-resistant depression. A committee of ten Spanish psychiatrists reviewed recent literature and developed consensus statements on TRD definitions, clinical response criteria, and the role of intranasal esketamine, which improves neuroplasticity and synaptogenesis. They highlighted therapeutic inertia—its causes and consequences—and produced a treatment algorithm that includes specific response evaluation steps to avoid inertia and ensure adequate treatment. This is the first Spanish consensus on theoretical aspects of TRD and intranasal esketamine's place in therapy.

Study at a glance

Abstract

Introduction Depression is a highly prevalent disease that severely impacts the life of patients. Inadequate response to at least two antidepressants despite adequacy of treatment and adherence is known as treatment-resistant depression (TRD), which entails a higher social and economic burden than non-resistant major depression. The lack of consensus on the definition of TRD and other aspects complicates management of the disease. Intranasal esketamine has a novel mechanism of action that differs from that of traditional antidepressants by improving neuroplasticity and synaptogenesis. Material and methods A scientific committee comprising ten psychiatrists, experts in TRD in Spain, reviewed the literature (grey literature and articles or scientific communications published between January 2014 and January 2024 in PubMed) and developed statements on theoretical and conceptual aspects of TRD. Statements were developed in a first meeting following a discussion group approach, refined in a second meeting following a nominal group technique, and consensus was finally drafted in a third meeting. Results A series of statements and recommendations were developed. Definitions for TRD and clinical response were proposed. The impact of therapeutic inertia was highlighted, identifying its causes and consequences. The role of intranasal esketamine in the TRD therapeutic treatment landscape was reviewed, and a treatment algorithm was developed, including specifics on evaluation of response to avoid therapeutic inertia and ensure an adequate treatment. Conclusions This is the first consensus developed in Spain regarding theoretical aspects of TRD and the role of intranasal esketamine in TRD therapeutic approach. A definition of TRD was proposed, together with a treatment algorithm.