Esketamine nasal spray for treatment-resistant depression

1.1 Esketamine nasal spray with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is not recommended, within its marketing authorisation, for treatment-resistant depression that has not responded to at least 2 different antidepressants in the current moderate to severe depressive episode in adults.

1.2 This recommendation is not intended to affect treatment with esketamine that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

The company positioned esketamine nasal spray for people who have had at least 3 antidepressants before, with or without another treatment like lithium or an antipsychotic medicine. This is narrower than the marketing authorisation, and also how clinical experts advised esketamine would likely be used in NHS practice.

The clinical evidence at this positioning is uncertain because it only considers a small number of people from the full clinical trial population. But it suggests that for people who have had at least 3 antidepressants with or without another treatment, esketamine with an SSRI or SNRI is likely more effective than placebo with an SSRI or SNRI. Because the trials were short the long-term benefits of esketamine are uncertain.

Also, the trial evidence excluded people with characteristics of depression like psychosis or recent suicidal ideation with intent. This limits how well the evidence applies to the NHS, because people having treatment for depression in the NHS may have psychosis or recent suicidal ideation with intent.

The clinical uncertainty means the economic modelling is also uncertain, including:

The limitations in the clinical evidence and economic model mean it is not possible to determine a reliable cost-effectiveness estimate. Esketamine is unlikely to be an acceptable use of NHS resources, so it is not recommended. Further research is recommended to address some of the uncertainties.