Treatment Resistant Depression with Loss of Antidepressant Response: Rapid-Acting Antidepressant Action of Dextromethorphan, A Possible Treatment Bridging Molecule.
Psychopharmacology bulletin August 15, 2016 Edward C Lauterbach
Dextromethorphan (DM) can produce a rapid-acting antidepressant effect in treatment-resistant unipolar major depressive disorder (MDD), similar to ketamine. In a patient who had failed adequate trials of citalopram and vortioxetine and lost response to fluoxetine and bupropion, a 300 mg oral loading dose of DM followed by 60 mg twice daily led to improvement within 48 hours that lasted 7 days and was sustained up to 20 days with daily administration, after which the response gradually waned over 7 days. The effect is thought to involve mTOR activation, NMDA receptor antagonism, sigma-1 and beta adrenergic receptor stimulation, and serotonin transporter inhibition.