Hi All,
Related to this journal club...the FDA announced restrictions on use of esketamine. What are peoples reactions to this?
link: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm632761.htm?utm_campaign=FDA%20approves%20new%20therapy%20for%20treatment-resistant%20depression.%20This%20th&utm_medium=email&utm_source=Eloqua
SG
Hi Seth and colleagues,
I have a lot of thoughts about the approval of esketamine for TRD, as well as about the REMS program and protocols required by the FDA for administration. First, I think that esketamine might represent a hugely important tool for the treatment of TRD, perhaps most notably in very acute depressive situations where acute suicide risk is very high. As we come out of a relatively stagnant era in terms of development of efficacious, practical therapies for depression and move into a future of novel targets and mechanisms, there are several considerations that I think are important to keep in mind. Ketamine, psilocybin, and MDMA, for example, represent huge potential breakthroughs in the treatment of depression. However, because they produce such robust effects on the brain and mind/psyche, and have such distinct phenomenological elements (increased potential to be psychologically traumatizing) when compared to tradition antidepressent medications like SSRIs, SNRIs, TCAs and MAOIs, they demand careful consideration of appropriate protocols for safe administration. I think that the FDA's decision to restrict esketamine to licensed/certified facilities and providers with specific training is generally wise. There is notable abuse potential, and the effects of the medication are such that the dissociative state encountered by many might present a very real safety issue if used in an uncontrolled environment. I think it is reasonable for us as the psychiatric prescribing community to be concerned about this, but also to advocate to maximize access for those who need it most. The risk of such a restrictive protocol is decreased access or feasibiltiy due to time/travel buren, though the benefit is decreased liability for providers, drug-makers, and insurers, and increased safety for patients. It will be interesting to see how this pans out over the next several years. I foresee robust use in inpatient/IOP/PHP kinds of settings - as many patients in these settings have TRD and these are the settings best equipped logistically to implement the strict protocol.
Regarding the JAMA-published E/S trial, though short duration and moderately powered, there were overwhelmingly positive results and a very robust treatment effect which appears to persist for some time after only a few treatments (as few as 1). Though this study appears to be well-done and rigorous, large effects like this are rare, encouraging, and slightly suspicious. I would love to see larger, multi-center trials verifying this outcome, as well as exploration of alternatives to the currently very-restrictive protocol to increase access. Dose-finding studies, larger RCTs looking at many more dependent measures, and post-market surveillance/empirical clinical analysis will help further elucidate the proper role of intranasal esketamine in the treatment of TRD>
Sorry for the late response - thanks for this article!