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

Pharmacological management of major depressive disorder has traditionally relied on antidepressants targeting the monoaminergic pathway. Treatment-resistant depression (TRD) patients have been frequently excluded from registrational trials, resulting in a lack of clear clinical recommendations for an optimised management. In recent years, treatments based on other mechanisms of action have been developed and approved. Intranasal esketamine is a novel non-monoaminergic treatment directed to improve neuroplasticity through the modulation of the glutamatergic system. In this clinical consensus we aimed to provide expert guidance on the use of intranasal esketamine for TRD patients based in our clinical practice in Spain. A scientific committee of nine psychiatrists, experts in TRD in Spain, reviewed the literature (grey literature and articles/scientific communications published in English or Spanish between January 2014 and January 2024 in PubMed). Statements on practical aspects of TRD management with intranasal esketamine were developed in a first meeting following a discussion group approach, refined in a second meeting with a nominal group technique, and finally drafted after consensus in a third meeting. We recommend a treatment algorithm for the management of TRD with intranasal esketamine. Recommendations were made for specific clinical profiles with other psychiatric comorbidities, which are not contraindications, and for patients who do not have at least a 50 % reduction in symptoms during the first induction phase (partial responders at the end of an induction phase). Treatment should be given in the same health centre where the patient normally receives mental care. The patient’s clinical progress will determine early optimisation of intranasal esketamine dose during the induction phase, the need for flexible doses/repeating the induction treatment phase, customisation of management, and treatment duration. We described factors impacting the use of intranasal esketamine and made recommendations on the characteristics of the ideal setting for its administration. Socio-economic aspects of intranasal esketamine were reviewed. This is the first consensus developed in Spain regarding practical aspects of TRD management with intranasal esketamine, with a treatment algorithm for patients who are only partial responders at the end of the induction phase.