Case Report: Oral glutamatergic augmentation for trauma-related disorders with fluoxetine-/bupropion-potentiated dextromethorphan ± piracetam: a four-patient case series.
Frontiers in Psychiatry 2026 DOI: 10.3389/fpsyt.2026.1752101 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case series Case report Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Patients with hard-to-treat trauma-spectrum disorders |
| Interventions | Dextromethorphan Fluoxetine Piracetam Bupropion |
| Duration | Days to weeks (intervention and follow-up period not explicitly stated) |
| Topics | PTSD |
| Keywords | Ampa Nmda Glutamatergic Trauma |
| Key findings | An oral dextromethorphan-based protocol potentiated by fluoxetine produced clinically meaningful symptom improvement within days to weeks in four patients with trauma-spectrum disorders, with no documented episodes of dissociation, hypertension, or mania. |
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.
Comparable studies
Other case reports and case series on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example. One couple with PTSD and a severe trauma history, participating in a pilot trial... | 2019 | Case study | n = 2 |
| Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series Veterans with co-morbid depression and PTSD | 2022 | Retrospective case series | n = 35 |
| Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder Patients with treatment-resistant depression and comorbid PTSD | 2023 | Case series | n = 5 |
| Treatment of nightmares in the context of posttraumatic stress disorder A client with chronic, severe posttraumatic stress disorder (PTSD) | 2010 | Case study | n = 1 |
| 5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study 23-year-old female with chronic refractory PTSD | 2023 | Case study | n = 1 |
Citations in the library
Cites 8
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
- Long term structural and functional neural changes following a single infusion of Ketamine in PTSD Neuropsychopharmacology June 3, 2023
- Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder Clinical Psychopharmacology and Neuroscience July 17, 2023
and 3 more in the library