Bridging Nonconsecutive Esketamine Weeks with Bupropion and Over-the-Counter Dextromethorphan
Richard Colby, Thomas L. Schwartz
Psychopharmacology Bulletin October 29, 2026 DOI: 10.64719/pb.21636 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | 52-year-old woman with treatment-resistant depression and bipolar II disorder |
| Interventions | Esketamine Dextromethorphan Bupropion extended-release |
| Dose | Esketamine not stated; dextromethorphan 45 mg twice daily; bupropion XL 450 mg daily |
| Measures | Patient Health Questionnaire-9 (PHQ-9) |
| Topics | Esketamine |
| Key findings | The patient's PHQ-9 dropped from 27 at baseline to 4 (±1) during weekly esketamine maintenance, but delayed sessions raised scores by up to 8 points. Adding over-the-counter dextromethorphan (45 mg twice daily) with bupropion XL (450 mg daily) reportedly allowed esketamine every 14 days without depressive relapse. |
Abstract
Frequent clinic visits required for maintenance intranasal (IN) esketamine therapy can limit treatment feasibility. Our case presents a 52-year-old woman with treatment-resistant depression (TRD) and bipolar II disorder (BD-II) who achieved sustained remission with weekly esketamine, but consistently experienced relapse of depressive symptoms when treatment intervals extended beyond 10 days. Her Patient Health Questionnaire-9 (PHQ-9) score decreased from 27 at baseline to 4 (±1) during maintenance treatment; however, with even a single delayed session, her PHQ-9 score could increase by as many as 8 points (from 4 to 12). To prevent relapse when she could not receive esketamine weekly, she began taking over-the-counter (OTC) dextromethorphan (DXM) and continued bupropion extended-release (XL), which she started prior to esketamine treatment. With 45 mg twice daily (BID) DXM and 450 mg daily bupropion XL, she was able to tolerate every-other-week administration of esketamine without depressive relapse. DXM and esketamine are both believed to function via antagonism of N-methyl-D-aspartate (NMDA) receptors. Bupropion is a competitive inhibitor of cytochrome P450 2D6 (CYP2D6), which is involved in the metabolism of DXM and maintenance of serum DXM concentration.1 As our patient was already taking bupropion XL, beginning OTC DXM was a low-cost option that we hoped would prevent relapse via continued NMDA antagonism in esketamine’s absence. To date, she is stable on a regimen of esketamine administration every 14 days, followed by 1 week of BID OTC DXM, to bridge esketamine doses and maintain NMDA antagonism, without return of depressive symptoms.
Comparable studies
Other case reports and case series on esketamine, most cited first.
Citations in the library
Cites 3
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Bupropion-Memantine Combination in the Treatment of Major Depressive Disorder and Treatment-Resistant Depression. Human psychopharmacology May 2026
- Classics in Chemical Neuroscience: Dextromethorphan (DXM). ACS Chemical Neuroscience June 21, 2023