A nasal spray for treatment-resistant depression has not been recommended by NICE because of uncertainties over its clinical and cost effectiveness.
Esketamine (Spravato) with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) is not recommended, within its marketing authorisation, for adults with treatment-resistant depression that has not responded to at least two different antidepressants in the current moderate to severe depressive episode.
Esketamine has the same molecular makeup as ketamine known as a party drug under the street name “Special K”. Studies suggest these medications should be limited to adults with treatment-resistant depression, without a history of substance or alcohol abuse disorders and without significant other medical conditions.
Current NHS practice is to manage treatment-resistant depression with oral antidepressants, then a second drug if symptoms do not improve. Alternative treatments can be used if oral treatments do not work. Drug treatment can also be combined with psychological therapy.
Introduction of esketamine in the NHS will be complex
Meindert Boysen, director of the centre for health technology evaluation at NICE, said: “Our independent committee very much recognises the impact treatment-resistant depression has on people, their families and carers, the clear need for effective alternative treatment options, and the priority of addressing mental health challenges for the NHS.
"Introduction of esketamine into clinical practice in the NHS will be complex because the structure and delivery of services would need to be changed. Estimates of the costs of providing the clinical service for esketamine were highly uncertain, as are the costs of repeated courses of the drug.
"There is a lack of evidence comparing esketamine with all relevant comparators, and the committee concluded that the estimates of cost effectiveness were likely to be much higher than what the NHS usually considers value for money.”
Evidence from clinical trials suggest that esketamine with an oral antidepressant may be more effective at relieving the symptoms of depression than placebo and an oral antidepressant. But how much benefit it provides over other oral antidepressants with antipsychotics or lithium adjunctive therapy, oral antidepressants combined, or other alternative treatments is unclear because these treatments have not been compared directly. Also, the available evidence did not include psychological therapies.
In addition there is uncertainty about the effect of stopping esketamine treatment. It is unclear if any improvements in symptoms will be maintained after a course of treatment and whether this will improve someone’s quality of life. Therefore the costs of possible repeated courses of treatment with esketamine are unknown, as are the costs of providing the clinic service for esketamine.
The cost-effectiveness estimates for esketamine are likely to be much higher than what NICE usually considers to be a cost-effective use of NHS resources, so it cannot be recommended.
The draft guidance is subject to consultation. Consultees and commentators can have their say via nice.org.uk until 18th February 2020.