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

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.