Case Report: Oral glutamatergic augmentation for trauma-related disorders with fluoxetine-/bupropion-potentiated dextromethorphan ± piracetam: a four-patient case series.

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.