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

Four patients with hard-to-treat trauma-spectrum disorders—somatic PTSD, acute bereavement-related PTSD, trauma-linked adolescent depression, and complex PTSD with bipolar II, ADHD, and borderline features—showed clinically meaningful symptom improvement within days to weeks after starting an inexpensive oral protocol centered on dextromethorphan potentiated by fluoxetine, with optional piracetam or bupropion. Reductions in intrusive memories, rumination, somatic pain, and functional disability were noted; no episodes of dissociation, hypertension, or mania were clinically documented during follow-up, though structured screening for hypomania and serotonergic toxicity was not performed. The findings are hypothesis-generating and suggest further controlled investigation of oral NMDA-AMPA modulators for trauma-related conditions.

Study at a glance

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.