Case Report: Oral glutamatergic augmentation for trauma-related disorders with fluoxetine-/bupropion-potentiated dextromethorphan ± piracetam: a four-patient case series.
Frontiers in psychiatry January 1, 2026 Peer reviewed DOI: 10.3389/fpsyt.2026.1752101 via PubMed
Summary
Four patients with hard-to-treat trauma-spectrum disorders, including PTSD and complex PTSD, experienced clinically meaningful symptom improvement within days to weeks using a treatment protocol centered on dextromethorphan (DXM) and fluoxetine. Notable reductions were observed in intrusive memories, rumination, somatic pain, and functional disability, with no documented episodes of dissociation or hypertension during follow-up. These findings suggest potential for further investigation into NMDA-AMPA modulators for trauma-related conditions.
Study at a glance
| Design | case study |
|---|---|
| Sample size | 4 |
| Population | patients with hard-to-treat trauma-spectrum disorders |
| Key finding | All four patients showed notable reductions in intrusive memories, rumination, somatic pain, and functional disability. |
Abstract
Traditional monoaminergic medications often offer limited relief for the physical and cognitive symptoms of post-traumatic stress disorder (PTSD) and complex PTSD. Growing data now point to fast-acting, glutamate-based treatments that boost synaptic plasticity and interrupt fear-conditioned neural circuits. We report four sequential cases of hard-to-treat trauma-spectrum disorders-somatic PTSD, acute bereavement-related PTSD, trauma-linked adolescent depression, and complex PTSD complicated by bipolar II disorder, ADHD, and borderline features-that showed clinically meaningful symptom improvement, typically within days to weeks, with an inexpensive, fully oral protocol centred on dextromethorphan (DXM) potentiated by fluoxetine, with optional add-on piracetam and/or bupropion. All four patients showed notable reductions in intrusive memories, rumination, somatic pain, and functional disability; no episodes of dissociation, hypertension, or mania were clinically documented during follow-up, although structured screening for hypomania/mania and serotonergic toxicity was not performed. These findings are strictly hypothesis-generating and broaden the ketamine/Auvelity framework to trauma-spectrum presentations. They suggest that further controlled investigation into oral NMDA-AMPA modulators may be warranted for trauma-related conditions.