Treatment Resistant Depression with Loss of Antidepressant Response: Rapid-Acting Antidepressant Action of Dextromethorphan, A Possible Treatment Bridging Molecule.
Edward C Lauterbach
Psychopharmacology Bulletin August 15, 2016 DOI: 10.64719/pb.4347 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | Patient with treatment-resistant unipolar major depressive disorder |
| Intervention | Dextromethorphan |
| Dose | 300 mg oral loading dose, then 60 mg po bid |
| Duration | Rapid effect within 48 hours, lasting 7 days, sustained up to 20 days with daily administration |
| Topics | Depression Ketamine |
| Keywords | N-methyl-d-aspartate Antidepressant agents Aripiprazole Receptors – ampa Serotonin uptake inhibitors Sigma Treatment – resistant |
| Key findings | Dextromethorphan produced a rapid-acting antidepressant effect within 48 hours in a patient with treatment-resistant unipolar MDD, lasting up to 20 days with daily administration. |
Abstract
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.1,2 This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days. Upon full relapse in DSM-5 MDD while taking 600 mg/day of the strong CYP2D6 inhibitor bupropion XL, a 300 mg oral loading dose of DM was given, followed by 60 mg po bid after an additional dose-finding period, without side effects. DM exhibited a ketamine-like rapid-acting antidepressant effect, thought to be mediated by mTOR activation (related to NMDA PCP site antagonism, sigma-1 and beta adrenergic receptor stimulation) and 5HTT inhibition, resulting in AMPA receptor trafficking, and dendritogenesis, spinogenesis, synaptogenesis, and increased neuronal survival (related to NMDA antagonism and sigma-1 and mTOR signaling). This report appears to be the first report of a rapid-acting effect in unipolar MDD and adds to antidepressant effects observed in the retrospective chart review of 77 patients with Bipolar II Disorder (Kelly and Lieberman 2014). If replicated, there is some reason to think that the administration of other agents with DM, such as lithium or D-cycloserine, might prolong the duration of the rapid-antidepressant effect.
Comparable studies
Other case reports and case series on ketamine for depression, most cited first.