Clinical guidance on the use of esketamine nasal spray for patients with treatment resistant depression: A European Delphi consensus report

AI Summary

Continue esketamine nasal spray despite modest acute symptom reductions, particularly with long disease course or multiple therapy resistance, to support clinical benefit.
Maximise dose and frequency to 84 mg weekly where indicated, tailoring regimen to individual clinical characteristics to enhance acute phase outcomes.
Monitor residual symptoms, functional recovery and comorbidity; prolong maintenance ≥12 months based on clinical worsening when tapering, relapse risk, chronicity and recurrence history.

Eur Neuropsychopharmacol. 2026 Jul 17;113:112907. doi: 10.1016/j.euroneuro.2026.112907. Online ahead of print.

ABSTRACT

Esketamine nasal spray (NS) is an established treatment for patients with treatment resistant depression (TRD). To further optimise real-world outcomes, consensus is needed regarding strategies to enhance patient outcomes and decision-making factors for pivotal timepoints in esketamine NS treatment. This modified Delphi panel (3 rounds) established expert consensus (≥80% agreement) from 30 European psychiatrists experienced in management of patients with TRD receiving esketamine NS. During the acute phase (4-12 weeks), modest/subjective reductions in core symptoms important to both patients and physicians supported esketamine NS continuation, especially with long disease course/resistance to multiple therapies. Consensus was reached that such a modest improvement during the acute phase should justify esketamine NS continuation (and supplementation of other treatment modalities with esketamine NS). Esketamine NS dose/frequency maximisation (84 mg weekly) was advocated for, to enhance acute phase outcomes, alongside strategies reflective of individual clinical characteristics. Monitoring in the continuation phase (6-9 months) should prioritise residual/fluctuating symptoms, changes in symptom severity, functional recovery status and comorbidity management/emergence. Should residual symptoms persist, dose/frequency escalation, among other all-phase options, were supported. Prolonging maintenance phase treatment (≥12 months) depended on the degree of clinical worsening when tapering, the risks/consequences of relapse, chronicity of the last depressive episode, residual symptoms and recurrence history. Across all phases, recommended treatment plans included integration of psychotherapy, optimisation of concomitant antidepressants/augmentation strategies, comorbidity management and strengthening support networks. Overall, the consensus advocated for an approach reflective of TRD complexities, prioritising meaningful outcomes for individual patients.

PMID:42468081 | DOI:10.1016/j.euroneuro.2026.112907

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