Cheung’s Regimen Series: Successful Conversion From One Dose of Esketamine to a Low-Cost Oral Ketamine-Class Glutamatergic Regimen in Treatment-Resistant Depression and OCD

Intranasal esketamine has proven its worth for patients whose depression will not yield to standard medicines, yet the realities of cost and clinic-based monitoring bar many people from long-term use. The situation is especially frustrating for those who respond spectacularly to a first dose only to watch the benefits fade when they can no longer afford repeat treatments.That was the predicament of a 48-year-old office worker who, in 2023, received a single 56 mg spray of esketamine. Within hours his mood lifted and the suicidal thoughts that had haunted him for months vanished, but the HK $6,000 price tag of each session forced him to stop. Over the next two years his illness morphed into severe obsessive–compulsive disorder dominated by violent, self-directed images. Trials of flupentixol/melitracen, bupropion plus over-the-counter dextromethorphan, and other conventional combinations offered only fleeting relief.In 2025 we replaced that patchwork with a mechanistically guided, fully oral "ketamine-like" stack: dextromethorphan 120 mg/day to block NMDA receptors, fluoxetine 20–40 mg/day to slow dextromethorphan metabolism via CYP2D6 inhibition, and piracetam 1.2 g/day to boost downstream AMPA activity. A few low-dose adjuncts (risperidone, valproate, pregabalin) were retained for sleep and anxiety. Four weeks later the change was unmistakeable. Intrusive imagery that once erupted every hour now surfaced only sporadically and could be brushed aside. His PHQ-9 score fell from 17 to the 5–6 range, suicidal ideation disappeared, and he returned to full productivity at work. These gains have held steady for more than eight months at a monthly medication cost of roughly HK $400–600—less than one-tenth the expense of maintenance esketamine.The case suggests that patients who exhibit an early, dramatic response to esketamine may not need to choose between relapse and ruinous expense. A carefully constructed oral regimen that recreates ketamine's NMDA-to-AMPA plasticity cascade can deliver similar, durable results at a price most clinics and patients can manage. Systematic trials are now warranted to test whether this strategy can scale to the wider population for whom intravenous or intranasal ketamine is out of reach.