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

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.