Clinical guidance on the use of esketamine nasal spray for patients with treatment resistant depression: A European Delphi consensus report.
Allan H Young, Bernhard T Baune, Beatrice Benatti, Djamila Bennabi, Sven Estercam, Philip Gorwood, Luis Gutiérrez-Rojas, Vassilis Martiadis, Patricio Molero, Claus Normann, Richard Perry, William Pitchot, Andreas Reif, Gianluca Rosso, Eduard Vieta, Andrea Fagiolini
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology July 17, 2026 DOI: 10.1016/j.euroneuro.2026.112907 via PubMed
Summary
AI-generated from the abstractA panel of 30 European psychiatrists with expertise in treatment-resistant depression (TRD) reached consensus on strategies for using esketamine nasal spray across treatment phases. During the acute phase (4-12 weeks), even modest reductions in core symptoms support continuing esketamine, especially for patients with long disease course or resistance to multiple therapies. Dose and frequency maximization (84 mg weekly) was recommended to improve acute outcomes. In the continuation phase (6-9 months), monitoring should focus on residual symptoms, functional recovery, and comorbidities. Prolonging maintenance treatment (≥12 months) depends on the degree of worsening when tapering, relapse risk, and recurrence history. Across all phases, integrating psychotherapy, optimizing antidepressants, managing comorbidities, and strengthening support networks were recommended.
Study at a glance
| Characteristics | Modified Delphi panel Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | European psychiatrists experienced in managing patients with treatment-resistant depression receiving esketamine nasal spray |
| Intervention | Esketamine nasal spray |
| Dose | 84 mg weekly |
| Duration | Acute phase (4-12 weeks), continuation phase (6-9 months), maintenance phase (≥12 months) |
| Topics | Esketamine |
| Keywords | Assessment patient outcome Decision-making shared Delphi method Treatment resistant depression |
| Key finding | Expert consensus supported continuing esketamine nasal spray even with modest acute-phase improvement and advocated for dose/frequency maximization, while prolonging maintenance treatment depended on clinical worsening during tapering and relapse risk. |
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.