Oral Glutamatergic Augmentation for Trauma-Related Disorders with Fluoxetine- / Bupropion- Potentiated Dextromethorphan ± Piracetam: A Four-Patient Case Series
Research Square November 25, 2025 preprint DOI: 10.21203/rs.3.rs-8189081/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case series Case report |
|---|---|
| Sample size | 4 |
| Population | Patients with hard-to-treat trauma-spectrum disorders (somatic PTSD, acute bereavement-related PTSD, trauma-linked adolescent depression, complex PTSD with bipolar II disorder, ADHD, and borderline features) |
| Interventions | dextromethorphan fluoxetine piracetam bupropion |
| Topics | Neuroplasticity |
| Keywords | Dextromethorphan Monoaminergic Glutamatergic Piracetam Cognition Anesthesia Pharmacology |
| Citations | 1 |
| Key findings | An oral dextromethorphan-based protocol potentiated by fluoxetine led to swift, long-lasting remission of symptoms across four cases of treatment-resistant trauma-related disorders. |
Abstract
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 achieved swift, long-lasting remission with an inexpensive, fully oral protocol centered on dextromethorphan (DXM) potentiated by fluoxetine, with optional add-on piracetam and/or bupropion. Within days to weeks, all four patients showed striking declines in intrusive memories, rumination, somatic pain, and functional disability, and none experienced dissociation, hypertension, or mania. These findings broaden the ketamine/Auvelity framework to trauma-related illnesses and highlight the need for controlled studies of low-cost, readily available NMDA–AMPA modulators for both the prevention and treatment of PTSD.