Oral NMDA and AMPA Modulation for Refractory Obsessive-Compulsive Symptoms in Bipolar Disorder: A Case Series of Routine Clinical Outcomes

Comorbid obsessive–compulsive symptoms in bipolar disorder remain difficult to manage because serotonin-reuptake agents can trigger mood elevation while conventional mood stabilisers seldom relieve obsessions. Rapid-acting glutamatergic interventions such as intravenous ketamine improve both mood and intrusive thinking (1,2) yet are costly and logistically demanding. We describe three consecutive adults with bipolar disorder who showed severe, mood-congruent obsessive–compulsive phenomena—including trichotillomania, onychophagia and distressing somatic ruminations—despite multiple trials of high-dose SSRIs, SNRIs, atypical antipsychotics and standard mood stabilisers. During routine outpatient care between May and November 2025 each patient began an oral ketamine-mimetic programme — the Cheung Glutamatergic Regimen — built around dextromethorphan (NMDA antagonism) whose exposure was extended with a CYP2D6 inhibitor, then augmented with piracetam (AMPA positive allosteric modulation) and, when required, L-glutamine for presynaptic glutamate replenishment. All three individuals entered sustained remission of depressive, anxious and obsessive–compulsive symptoms after the sequential addition of piracetam to the dextromethorphan base, and the gains persisted through follow-up. Treatment was generally well tolerated; transient hypomanic activation was contained by reducing dextromethorphan or its metabolic inhibitor while maintaining piracetam. These naturalistic observations suggest that a wholly oral, low-cost NMDA–AMPA modulation strategy may offer a rapid and durable option for the "bipolar-OCD" phenotype. Formal controlled studies are needed to confirm efficacy, define optimal dosing and clarify long-term safety.