Eschewed outcome for Esketamine

NICE does not recommend Nasal Antidepressant. Is this NICE for patients?

Writer: Altay Altug Shaw
Editor: Similoluwa Ayeni-Yegbe
Artist: Cveta Gotovats


For a lot of people, the thought of dealing with mental health disorders is a frightening endeavour to contend with. It is thought that about a seventh of individuals in England, will report a common mental health problem per week. With only an estimated quarter of those with a condition receiving needed help, the drive for better support is ever present.

Esketamine was recently being touted as a new antidepressant medication. The drug acts on the NMDA receptor, an ion channel found on nerve cells. Targeting of such receptors has been the focus for treating neurodegenerative disorders such as Alzheimer’s and Parkinson’s. However, the issue with such targets, is trying to preserve normal physiological function, without targeting the boosting the negative attributes of previous conditions. 

For this reason, such treatments have been risky, especially with little known about long term effects of such medications. Esketamine itself is still in its infancy in that regard. Having previously been used as a general anaesthetic, US trials have shown its positive effects for those with previously untreatable depression.

Esketamine has had fast acting effects for individuals with treatment-resistant depression. In 2016, double blind trials for its delivery, demonstrated rapid mood improvements. This trial concluded that a dosage of 20mg/kg would be ideal to ensure treatment was successful as well as ensuring its tolerability. A further study conducted in 2018 demonstrated that the treatment of the drug persisted, up to 9 weeks after patients were taken off higher dosages of the drug. 

In a randomised clinical trial carried out in 2019, participants who had taken esketamine with an oral antidepressant took longer to relapse into depressive patterns of behaviour, as opposed to those receiving placebo following a test period of 16 weeks. Esketamine had shown a good short-term effect, previously unseen by other drugs in such trials.

This appeared to be a turning point for the anti-depressants in the USA. With an estimated 16 million individuals in the States diagnosed with depression, and the condition being the leading cause of disability worldwide, it reiterated the need for urgent action by healthcare systems to provide appropriate diagnoses and treatments. 

However, little research has been carried out into the long-term effects of withdrawal or reduced dosage of the medication. Despite FDA approval coming in February 2019, it seemed like not enough research had been carried out to detect all possible side effects.  Those receiving the medication in the USA, have experienced symptoms of disturbed speech, uncertainty and disequilibrium. In addition to this, the FDA reported 8 deaths following the use of esketamine after suicide related patterns of behaviour started to increase, though the FDA claimed it was not related to the use of the drug, due to “lack of a consistent pattern”.

On 28th January 2020, NICE made the announcement that it would not be recommending the use of esketamine with SSRIs (Selective serotonin reuptake inhibitors), for public use. It cited the lack of long-term evidence of withdrawal and side effects as well as a lack of comparison to medications being used today. NICE also questioned whether it was the medication or positive life choices that were having a beneficial effect on the individual, following the initial treatment.

Due to the unknowns and the costs involved, NICE has made no statements to whether the treatment will continue. The draft guidance that this verdict was given, stated that the cost of treatment was not worth the initial use of the medication.

In the meantime, it looks set that esketamine will not be used for official treatment in this country. Thus, the long wait for new and improved antidepressants continues.

Resources

1.       McManus S, Bebbington P, Jenkins R, Brugha T. (eds.) (2016). Mental health and wellbeing in England: Adult psychiatric morbidity survey 2014. Leeds: NHS digital.

2.       Survey shows one in three adults with common mental disorders report using treatment services – NHS Digital [Internet]. NHS Digital. 2020 [cited 15 February 2020]. Available from: https://digital.nhs.uk/news-and-events/news-archive/2016-news-archive/survey-shows-one-in-three-adults-with-common-mental-disorders-report-using-treatment-services

3.       Koch H, Szecsey A, Haen E. NMDA-antagonism (Memantine): An Alternative Pharmacological Therapeutic Principle in Alzheimers and Vascular Dementia. Current Pharmaceutical Design. 2004;10(3):253-259.

4.       Singh J, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G et al. Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biological Psychiatry. 2016;80(6):424-431.

5.       Daly E, Singh J, Fedgchin M, Cooper K, Lim P, Shelton R et al. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression. JAMA Psychiatry. 2018;75(2):139.

6.       Deaths, Serious Adverse Events, Adverse Events Leading to Study Withdrawal [Internet]. Fda.gov. 2020 [cited 15 February 2020]. Available from: https://www.fda.gov/media/121376/download

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