How Does Spravato / Esketamine Help with Depression?
By William Rayburn MD, MBA
Clinical Director, Spravato Treatment Program, Sweetgrass Psychiatry
Understanding how medications act on the brain can seem speculative and confusing. The predominant hypothesis of the mechanism of action of esketamine is illustrated in a video accessed at:
https://www.janssenmd.com/spravato/multimedia/SPR-001. Simply put, our brains contain nerve cells (or neurons) with specialized receptors and chemicals (called neurotransmitters) which vary in structure and function depending on the region of the brain. In depression, there are structural and functional impairments of synapses in brain regions involved with mood and emotional behavior. The well-established roles of monoamines (e.g., serotonin, norepinephrine, dopamine) and glutamate play important roles in regulating synaptic connectivity between neurons.
Medications prescribed for depression are intended to target specific systems of cell receptors (e.g., glutamatergic, GABAergic, opioidergic). The binding of the drug to certain receptors is believed to influence the neuron function by either stimulating (agonist) or suppressing (antagonist) its function. Selecting target receptors to stimulate or suppress provides many treatment options.
The precise mechanism of action of esketamine nasal spray in MDD is unknown. It is believed to not involve inhibition of serotonin, norepinephrine, or dopamine reuptake or directly involve mu-opioid receptor stimulation. You should understand that esketamine (SPRAVATO) acts differently by being a “non-competitive N-methyl D-aspartate (NMDA)” receptor antagonist. It is believed to act more rapidly than conventional antidepressants and, therefore, may enhance (or augment) the effect of your antidepressant by acting on a different receptor.
Major depression manifests itself in many ways which is why there needs to be a trial-and-error approach in prescribing, often with more than one medication. Taken alone, esketamine (SPRAVATO) has not been reported as a substitute for a different antidepressant, although a small number of our patients take SPRAVATO alone. Furthermore, while it is encouraging to hear about any relief of suicidal thoughts or anxiety, esketamine is not indicated for either condition.
If you have treatment resistant major depression, live in the Charleston SC or Mount Pleasant, SC area and are interested in scheduling a Spravato consultation, please call Sweetgrass Psychiatry at (843) 800-1303.