Sunday, 07.03.2021

Samuel Gershon: Ketamine the new "breakthrough" in the treatment of depression

 

Bruno Müller-Oerlinghausen’s comment

 

 

        I fully agree with Dr. Gershon’s critical attitude towards the official approval of the new Janssen product esketamine by the FDA and the EMA.

        Some British authors (Jauhar and Morrison 2019;  Mahase 2019) have expressed their well-founded skepticism as to the overall benefits of this new compound. Elisabeth Mahase refers to Prof. John Read, clinical psychologist, who expressed “grave concern” over esketamine potentially being approved in the UK. In fact, the National Institute for Health and Care  Excellence (NICE) did not recommend the new compound for being accepted within the NHS. There is no sufficient experience about the positive or negative long-term effects of the compound. Particularly irritating is the fact, also picked up by Schatzberg (2019), that the FDA mentions a number of studies not having been considered for the official approval process, from which it becomes evident that six completed suicides happened and that all of them were in the esketamine arm.

        Another reason for concern regarding the true safety profile of this compound is the observation, mentioned by Gastaldon, Papola, Ostuzzi and Barbui (2019), that 25 % (!) of the patients having been given esketamine acutely in three placebo-controlled trials developed severe dissociation, which might be considered a dangerous condition regarding the risk of suicide. I’m very sympathetic with the critical comment of the latter authors that it remains absolutely unclear whether the “rapid change in depression scores is due to an improvement of depression or just a temporary effect of the drug on some brain mechanisms.”

        It is my understanding the approval of this potentially dangerous compound by the European agency has been unnecessary and premature since its long-term safety so far remains unknown. My critical attitude is supported by Elisabeth Manase (2019), quoting Rupert Mc Shane, a member of advisory boards of Janssen who principally is sympathetic with the decision of the EMA: “We still have concerns... and are disappointed that the European license did not impose a requirement for patients taking it to be entered into a central registry that would enable the long-term outcomes to be tracked” (McShane 2019).

 

References:

Gastaldon C, Papola D, Ostuzzi G, Barbui C.  Esketamine for treatment resistant depression: a trick of smoke and mirrors? Epidemiol Psychiatr Sci. 2019; 29:e79.  

Jauhar S, Morrison P. Esketamine for treatment resistant depression. We should cautiously welcome this new therapeutic option.  BMJ 2019; 366:l5572.  

Mahase E. Esketamine is approved in Europe for treating resistant major depressive disorder. BMJ 2019; 367:l7069. 

McShane Rupert: A drug not a miracle - why we need a new system for monitoring ketamine. thebmjopinion, July 26, 2019. 

Schatzberg AF. A word to the wise about intranasal esketamine. Am J Psychiatry. 2019; 176(6):422-4.

 

October 1, 2020