Esketamine for Depression

This post will focus on Johnson & Johnson's NMDA intranasal Esketamine (form of Ketamine) for treatment resistant depression or (TRD), with rapid onset of effect. Esketamine has received breakthrough therapy designation (BTD) from the FDA in 2013 for treatment-resistant depression, and again in 2016 for major depressive disorder with imminent risk of suicide.  JNJ through Janssen has several Esketamine phase 3 clinical trials for TRD patients currently running. Results from a phase 2 clinical study for patients 20-64 years of age with treatment resistant depression, (lack of treatment with at least two different oral anti-depressants) released results.  The results by Janssen showed a statistically significant effect, with ascending dose-response relationship, and response was observed as quickly as two hours post dose.  The side effect profile is better explained here JAMA Psychiatry in etable 4 supplemental 1. A rundown of the side effect profile from that supplemental is below. 
                                                                56mg                     84mg
Dizziness                                                40%                         47%
Headache                                               15%                          18%
Dissociation                                           35%                         24%
Dysgeusia                                               15%                          29%
Nausea                                                    20%                         24%
Dissociative  Disorder                           5%                          24%               
Oral Hypoesthesia                               20%                          12%     

We'll have to see how the FDA addresses the side effect profile of the intranasal drug. Thank you for reading.
 

NMDA Receptor Modulators for CNS Disorders

We originally wrote about this topic here NMDA Receptor Modulators for Depression. There are now several companies interested in bringing a variety of NMDA drugs into the clinic, either as mono-therapy or coupled with enhancers.  Let's have a look at some of the companies, their drug, and indications that they are targeting.

Avanir:  Otsuka

AVP-786  Dextromethorphan + Quinidine
Ph 3  Agitation in Alzheimer's Disease
Ph 2  Residual Schizophrenia
Ph 2  Major depressive disorder (adjunct)

Axsome: AXSM

AXS-05  Dextromethorphan + Bupropion  

Ph 3 Treatment resistant depression

Ph 1 Agitation in Alzheimer's Disease

Cerecor:  CERC
CERC-301  NR2B Specific NMDA antagonist oral
Ph 2 Major depressive disorder (adjunct)

JNJ / Janssen
Esketamine  intranasal
Phase 3 adjunct with anti-depressant for TRD

Naurex:  Allergan
NMDA receptor partial agonist with selective properties
Ph 2 NRX-1074  IV
Ph 1 NRX-1074 Oral
Ph 3 GLYX-13 (Rapastinel) Weekly IV Major Depressive disorder

Vistagen:  VSTA
AV-101  NMDA selective antagonist oral
Ph 2 AV-101 Major depressive disorder 

Over the next couple years, we should see some meaningful clinical readouts from some of these companies.  Potentially NMDA drugs may provide for a more efficacious and safer, sustainable therapy, aside from current antidepressants for some of the above indications. Thank you for reading.