Oct 18, 2019: When is Spravato® indicated to treat depression?


As of March 6, 2019, the Food and Drug Administration (FDA) approved Spravato (esketamine) nasal spray, for adjunct treatment with an oral antidepressant, for treatment resistant depression.  This is the first time the FDA has approved esketamine for any use. Because of the risk of side effects and potential for misuse and abuse, Spravato is only available via a “restricted distribution system,” according to Dr. Tiffany Farchione, M.D. of the FDA. It must be administered in a certified medical office where the patient response can be observed. The patient must be monitored for a minimum of two hours post dose. The health care provider decides when the patient can safely leave the facility with someone else driving them home. The spray cannot be taken home by the patient.

Esketamine is the S-enantiomer of racemic ketamine. It is a non-selective and non-competitive antagonist of NMDA receptors.* 

Common side effects reported by at least 5% of patients include lethargy, sedation, dizziness, anxiety, increased blood pressure, vomiting, vertigo, dissociation, and feeling drunk. Patients with poorly controlled hypertension are at risk for more cardiovascular and cerebrovascular adverse effects. Emergence reactions have been reported in 12% of patients. In overdose, symptoms can include sedation and respiratory depression, altered mental status, hallucinations, emergence delirium, hypertension, and chest pain. Rhabdomyolyses has also been reported following agitation.

Treatment of overdose is symptomatic and supportive care. There is no antidote, but benzodiazepines can be administered for agitation or delirium.

If you have questions  about esketamine exposure, call the poison center at 1-800-222-1222.

Prepared by: Scott Muir RN, CSPI and Nena Bowman, PharmD, DABAT

The use of ketamine for treatment resistant depression was previously addressed in a Question of the Week (9/18/2017) titled “What is the Role of Ketamine in Major Depressive disorder?” written by Jose A. Arriola Vigo MD, a Psychosomatic Fellow in Psychiatry at that time 

I’m not sure how antagonism of the  NMDA receptors ameliorates depression-there are a lot of theories.  One of the theories is that blockade of NMDA receptors activates AMPA receptors which modulates a variety of downstream signaling pathways which influence neurotransmission.  There are probably multiple mechanisms by which it works with multiple impacts on synapses and signaling pathways. More to come, I’m sure. -ds

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vumc.org.


Donna Seger, MD

Executive Director

Tennessee Poison Center


Poison Help Hotline: 1-800-222-1222