Nasal Spray Depression Treatment Not Recommended by NICE

Nicky Broyd

January 28, 2020

Esketamine (Spravato, Janssen) nasal medication for treatment-resistant depression has been turned down in draft guidance by the National Institute for Health and Care Excellence (NICE) on cost and evidence grounds.

The rejection has brought a mixed reaction from experts.

'Lack of Evidence'

The new drug was assessed in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

It is given under supervision in a clinic to adult patients who have not  responded to at least two different antidepressants.

The list price for esketamine before any negotiated discounts is £163 for a 28 mg dose device. The company told NICE an average course of therapy would cost £10,554.25.

Currently treatment-resistant depression is managed with oral antidepressants which can be taken in combination with psychological therapy. Electroconvulsive therapy is another option if drug treatments have not worked.

NICE acknowledged clinical trial evidence suggested esketamine combination treatment may be more effective than placebo. However, the benefits over other combinations of treatments were not clear because direct comparisons had not been made.

Neither, NICE said, was it clear if treatment benefits would persist after stopping esketamine.

In a statement, Director of the Centre for Health Technology Evaluation at NICE, Meindert Boysen, said: there was a "clear need" for effective alternatives for treatment-resistant depression.

However, "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."


Last year, the US FDA approved esketamine for resistant depression, with some assessment panel members calling it a "game changer".

Several experts have reacted to the NICE decision via the Science Media Centre.

Dr Paul Keedwell, consultant psychiatrist, Cardiff University, said: "A substantial number of individuals suffering from major depression fail to respond to two or more conventional antidepressants. Existing approaches to treatment resistance, including medication combinations, talking therapy, or ECT, often fail, or are unacceptable. New approaches are required to reduce the costs to society of protracted suffering, disability and chronic health care needs.

"The NICE refusal to recommend intranasal esketamine for the management of treatment-resistant depression (TRD) will thus disappoint many sufferers in the UK who have failed to respond to existing treatments.

"The committee's objection to its use in TRD appears to be largely based on cost rather than lack of effectiveness."

Dr Sameer Jauhar, honorary consultant psychiatrist and research fellow, Institute of Psychiatry Psychology & Neuroscience, King's College London, said that "if one keeps to the evidence, it is hard to understand NICE's reasoning here.

"The crux of the matter, to my mind, are the latter points regarding continued use, benefit over the longer term, and associated economic costs.

"The modelling NICE uses has to be transparent, and it is, and this seems to be the most relevant argument for not sanctioning the use of esketamine here.

"In summary, the decision-making here appears based on longer-term use and demonstrable cost benefit.

"There will be similar compounds, with novel modes of action, becoming available over the coming years, and this patient group badly needs access to effective treatments, which will, in time, be evaluated by NICE."

However, Professor David Curtis, retired consultant psychiatrist and honorary professor at UCL and QMUL, said: "This new guidance from NICE seems very sensible. Many psychiatrists have been concerned at the lack of evidence that esketamine is really a helpful treatment for depression.

"There are also unanswered questions about the extent to which it might cause unwanted effects and how it could be safely used in practice. On this occasion NICE is quite correct to wait for additional information, including the results from further research, rather than allowing esketamine to be used in routine clinical practice."

Interested parties are able to have their say on the draft NICE guidance until 18th February this year.

Declared interests:
Dr Paul Keedwell:  No declarations of interest.
Prof David Curtis: No conflicts of interest.
Dr Sameer Jauhar: Did an editorial for esketamine for the BMJ. No Johnson and Johnson funding.

The National Institute for Health and Care Excellence (NICE): Esketamine for treatment-resistant depression (ID1414) In development [GID-TA10371] January 28th 2020.


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