Treating Obsessive-compulsive Disorders With the Cheung Glutamatergic Regimen

Cheung, Ngo

Cheung Ngo Medical

About this ebook

Obsessive-compulsive disorder (OCD) remains one of the most challenging conditions in clinical psychiatry. Even with optimal doses of serotonin reuptake inhibitors and adjunctive exposure-response prevention therapy, 40-60 % of patients experience persistent, treatment-resistant symptoms. For years, the field has searched for interventions that could more directly address the rigid, maladaptive synaptic patterns embedded within cortico-striato-thalamo-cortical circuitry. Intravenous ketamine provided a dramatic proof-of-concept: a single sub-anaesthetic dose could rapidly loosen obsessive thoughts and compulsive urges, often within hours, by transiently shifting glutamatergic balance from NMDA- to AMPA-dominant signaling.

Yet ketamine's logistical barriers-cost, need for monitored administration, and dissociative side effects-have limited its reach. The Cheung Glutamatergic Regimen (CGR) represents a bold, pragmatic attempt to translate ketamine's mechanistic insights into an accessible, fully oral protocol using existing, inexpensive medications: dextromethorphan (NMDA antagonism), a potent CYP2D6 inhibitor to prolong dextromethorphan exposure, piracetam as an AMPA positive allosteric modulator, and, when needed, L-glutamine to replenish presynaptic glutamate stores.

Dr. Cheung Ngo's work, compiled in this volume, offers the most extensive published clinical experience to date with this approach. The series spans adolescents and older adults, treatment-naive individuals and those with decades of illness, and a wide range of comorbid presentations-bipolar disorder, autism spectrum disorder, ADHD, and severe somatic/hypochondriacal themes. What emerges is a consistent pattern: rapid, clinically meaningful reductions in obsessive intensity and ritual frequency, often within days to weeks, particularly when pharmacokinetic exposure to dextromethorphan is adequately sustained and AMPA facilitation is layered on. In several cases, symptom relief proved durable for months without dose escalation or major adverse events.

This collection is not a definitive endorsement. The data are naturalistic, uncontrolled, and derived from a single clinician's practice. Formal Y-BOCS ratings are sparse, blinding is absent, and concomitant medications confound attribution. Yet the temporal associations-improvement tightly linked to the sequential addition of each component, relapse upon withdrawal, and remission upon reinstatement-are difficult to dismiss. The regimen's flexibility-bedtime-only dosing for many, split schedules for diurnal rebound, and careful titration to avoid serotonin toxicity or hypomanic activation-also speaks to real-world utility.

For clinicians managing treatment-resistant OCD, especially when standard serotonergic strategies have failed or are contraindicated, the CGR offers a rational, low-cost bridge between first-line therapy and resource-intensive interventions such as ketamine infusions. Dr. Cheung's careful documentation and mechanistic reasoning provide a compelling foundation for further investigation. Randomised, controlled trials-stratified by CYP2D6 genotype, incorporating neuroimaging of synaptic density, and extending follow-up beyond one year-are now essential to determine whether this oral ketamine-like approach can be reliably generalised.

Until such evidence arrives, this volume stands as a provocative, clinically grounded hypothesis: the same glutamatergic plasticity cascade that makes ketamine unique may be replicable, at scale, with agents already on pharmacy shelves.