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Esketamine for treating treatment-resistant depression

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1 Recommendations

1.1 Esketamine with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) is not recommended, within its marketing authorisation, for treating 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

Treatment for treatment-resistant depression includes oral antidepressants, which are sometimes used with antipsychotic drugs. Electroconvulsive therapy can be used if oral treatments do not work. Esketamine is a nasal spray taken with an SSRI or an SNRI. The person having esketamine must be supervised by a healthcare professional in a clinic.

Clinical trials suggest that esketamine with an SSRI or SNRI may be more effective than placebo with an SSRI or SNRI. But it is unclear how effective esketamine is because of the way the trials were done. Also, people who may have esketamine in the NHS might have more severe depression than people in the trials.

There are problems with the economic model because it does not reflect how treatment-resistant depression is treated in the NHS or how long an episode of depression lasts. There is also uncertainty about:

  • whether any improvements in symptoms continue after treatment stops and if this will improve someone's quality of life

  • the costs of repeated courses of treatment with esketamine

  • the costs of setting up treatment clinics, including how many nurses would be needed and making sure esketamine is subject to controlled drug requirements.

Taking this uncertainty into account, the cost-effectiveness estimates for esketamine are much higher than what NICE considers a cost-effective use of NHS resources. So, it cannot be recommended.