Longitudinal Management of Post-traumatic Brain Injury Bipolar-Spectrum Disorder With Low-Dose Oral Glutamatergic Augmentation: Extended Follow-Up Revealing Induction, Overshoot, Stabilization, and Transition to PRN Maintenance.

Bipolar-spectrum illness emerging after traumatic brain injury (TBI) can be difficult to treat and may present with mixed or agitated depressive features that appear sensitive to glutamatergic modulation. In post-TBI cases, diagnostic certainty is often limited because irritability, impulsivity, sleep disturbance, affective lability, and cognitive change may overlap with frontal-limbic injury syndromes. This case is, therefore, framed as probable bipolar-spectrum disorder secondary to TBI rather than definitive idiopathic bipolar disorder. The Cheung Glutamatergic Regimen (CGR)--low-dose dextromethorphan with CYP2D6 inhibition plus piracetam--is used here only as a shorthand for an open-source, free-to-use, non-proprietary combination of off-patent components, not as a branded product. This report describes a woman in her mid-thirties with right frontal atrophy after a 2009 subdural hematoma who later developed probable bipolar-spectrum illness. On 21 October 2025, she presented with severe depressive relapse, insomnia, persistent rumination, irritability, and hypnagogic phenomena, with a Patient Health Questionnaire-9 (PHQ-9) score of 22. After partial improvement on valproate, risperidone, and Deanxit, dextromethorphan 30 mg nightly and piracetam 600 mg nightly were added on 5 November 2025. Within weeks, rumination decreased and mental flexibility improved, but transient mild hypomanic or frontal-disinhibition-like symptoms emerged, especially inappropriate laughter with a moria-like quality. She self-reduced dextromethorphan to 22.5 mg, piracetam was increased, and euthymia returned. Over the next six months, PHQ-9 scores improved to 10-12 and Generalized Anxiety Disorder-7 (GAD-7) scores to 8-13, with functional gains including exercise and motorcycle riding lessons. Later medications included aripiprazole, paroxetine-controlled release, pregabalin, and low-dose quetiapine. By April 2026, dextromethorphan and piracetam were used as needed during stress-related or premenstrual dips. No further psychotic symptoms were reported, and later mild dissociative or cognitive complaints became manageable after dose adjustment. This single-patient course suggests a three-phase pattern: induction with a narrow therapeutic window and brief activation/overshoot, stabilization after titration, and later PRN maintenance. Dextromethorphan appeared temporally most linked to both clinical benefit and transient activation, while piracetam may have acted as a modulator. However, causal inference is limited by the uncontrolled design, early PHQ-9 improvement before CGR initiation, later polypharmacy, unmeasured pharmacokinetics, absence of standardized mania/cognitive measures, and incomplete PRN-frequency documentation. The case is also only hypothesis-generating in relation to transcriptomic findings implicating bipolar-specific plasticity-related biology. Low-dose oral glutamatergic augmentation may warrant study as a closely monitored induction and consolidation strategy in post-TBI bipolar-spectrum illness, but prospective controlled trials are needed before broader recommendations can be made.