Oral Glutamatergic Augmentation for Trauma-Related Disorders with Fluoxetine- / Bupropion- Potentiated Dextromethorphan ± Piracetam: A Four-Patient Case Series
OpenAlex – November 25, 2025
Source: OpenAlex
Summary
Patients with hard-to-treat trauma-spectrum disorders experienced rapid and lasting remission using an oral protocol centered on dextromethorphan (DXM) and fluoxetine. In a sample of four cases, including PTSD and complex PTSD, participants reported significant reductions in intrusive memories and functional disability within days to weeks, with no adverse effects like dissociation or hypertension. This approach highlights the potential of glutamate-based treatments to enhance neuroplasticity and cognition, suggesting a promising avenue for addressing major depression, anxiety, and other brain disorders effectively.
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.