Case Series: Marked Improvement in Treatment-Resistant Obsessive–Compulsive Symptoms with Over-the-Counter Glutamatergic Augmentation in Routine Clinical Practice

Background: A sizeable minority of people with obsessive–compulsive disorder (OCD) remain haunted by intrusive thoughts and exhausting rituals even after lengthy courses of high-dose selective serotonin reuptake inhibitors (SSRIs) and antipsychotic add-ons. Because mounting basic-science and imaging data point toward glutamatergic imbalance in OCD, clinicians have begun to explore medicines that target glutamate rather than serotonin alone. Case series: Four consecutive patients—three adults and one 15-year-old—were seen in a community outpatient practice after standard treatments had failed to ease their severe OCD. Each patient was taking (or was started on) fluoxetine 10–40 mg/day, chosen both for mood stabilisation and for its ability to slow CYP2D6 metabolism. Over-the-counter dextromethorphan was then introduced at 30–120 mg/day, divided two or three times daily, making use of the drug’s mild NMDA-receptor blockade. Two patients who continued to report mental fog and vivid intrusive images later received piracetam 1 200 mg/day for its positive allosteric effect on AMPA receptors. Follow-up occurred during routine office visits; no research-specific procedures were added. Results: Within two to four weeks of starting dextromethorphan, all four patients described fewer and less intense obsessions, longer delays before engaging in compulsions, and improved sleep. The two individuals given piracetam reported additional gains in mental clarity and a further drop in obsessive content that persisted for at least eight weeks. Side-effects were mild: one brief episode of tachycardia that resolved after a small SSRI dose reduction, mild tremor in two patients, and transient menstrual spotting in one. No dissociative or psychotic reactions were observed. Conclusion: In this small, naturalistic series, adding low-cost glutamatergic agents—dextromethorphan with or without piracetam—to ongoing fluoxetine was linked to meaningful symptom relief in otherwise treatment-resistant OCD.