Slow Remission of Complex PTSD with Intermittent Exacerbations: A Case-oriented Review on Trauma and Neuroplasticity

Conventional monoaminergic medication seldom produces sustained remission in complex post-traumatic stress disorder (C-PTSD) that follows prolonged interpersonal trauma. Pre-clinical and clinical data now point to glutamatergic approaches that enhance synaptic plasticity as a promising alternative. We describe a 23-year-old woman with C-PTSD after years of school bullying who presented with intrusive memories, rumination, chest tightness, dyspnoea, avoidance, anxiety, low mood and academic dysfunction. An initial trial of fluoxetine-augmented dextromethorphan (DXM) was curtailed by gastrointestinal intolerance. Bupropion XL 150 mg each morning was substituted to inhibit CYP2D6, permitting DXM escalation from 30 mg to 60 mg (mainly nocte). Piracetam was introduced and titrated to 1 200 mg daily, and l-glutamine 500 mg nightly was added later. Across four months the Patient Health Questionnaire-9 fell from 24 to 15 and the Generalised Anxiety Disorder-7 from 20 to 15. Somatic anxiety resolved, rumination and benzodiazepine use declined, sleep and concentration improved, and only occasional nightmares or flashbacks persisted. No dissociation, hypertension or manic switch occurred. These observations are consistent with sustained NMDA antagonism, AMPA potentiation and downstream BDNF-mTOR activation, echoing ketamine’s mechanism but achieved with inexpensive oral agents. The case supports further controlled evaluation of oral psychoplastogen “stacks” for refractory C-PTSD.