Dextromethorphan
Novel (glutamate NMDA antagonist, serotonin reuptake inhibition)
- Bipolar Depression4
- Treatment resistant depression2
- Pseudobulbar affect (as Neudexta with quinidine)
- Agitation in dementia (as Neudexta with quinidine or as Auvelity)2
- OCD3
- Schizophrenia (clozapine augmentation)
- Misuse potential but not controlled
Features
Dosing
Dextromethorphan 15-30 mg bid as monotherapy in bipolar depression, or augmented with bupropion 200-300 mg/day in unipolar.
For OCD or clozapine augmentation, 30 mg/day (used in trials without a CYP2D6).
Can also use liquid OTC (dextromethorphan ER 30mg/5mL take 7.5ml bid) but prefer prescription tabs (less abuse potential).
Management
Works on own or as a quinidine-combination (Neudexta) for bipolar depression and TRD. Higher dose of dextramethorphan (30 mg bid) may also work. Quinidine prolongs the half-life of dextromethorphan (and raises levels) through CYP2D6 inhibition, but should only be used in 10 mg dose (which is available in Neudexta or through compounding pharmacies). Bupropion and some SSRIs also inhibit CYP2D6 (fluoxetine, paroxetine, and sertraline at 150mg or above).
EMR Text
Depression
Dextromethorphan use based on controlled trials in Major Depressive Disorder and FDA approval for this condition as a combination therapy with bupropion (Maji S et al, Psychiatry Res. 2024;342:116257).
Dextromethorphan side effects reviewed with patient.
Bipolar Depression
Dextromethorphan use based on controlled trials in bipolar depression (Chen SL et al, Eur Neuropsychopharmacol. 2014;24(11):1753-1759).
Dextromethorphan side effects reviewed with patient.
OCD
Dextromethorphan use based on a controlled trial in OCD (Zolghadriha A et al, Health Science Reports 2026;9:e72055).
Dextromethorphan side effects reviewed with patient.
Schizophrenia
Dextromethorphan use based on a controlled trial as augmentation in schizophrenia (Hegde NC et al, Asian J Psychiatry 2026;119:104919).
Dextromethorphan side effects reviewed with patient.
Agitation in Dementia
Dextromethorphan use based on controlled trials in agitation in dementia where it worked on its own (Cummings JL et al, JAMA. 2015;314(12):1242-1254) and FDA approval (as Auvelity).
Dextromethorphan side effects reviewed with patient.