Cheung's Regimen Series: Ultra-Low-Dose Paroxetine as CYP2D6 Inhibitor Enables Safe OTC Glutamatergic Augmentation in a Depressive Patient on Lisdexamfetamine

A 35-year-old office worker came to our clinic after years of unrelieved depression, mounting anxiety, and lifelong distraction. Several antidepressants had failed, and a recent hospitalisation for suicidal thoughts underscored the urgency of her situation. Morning lisdexamfetamine 20 mg sharpened her focus but left mood and worry largely untouched. Because she had not responded to serotonergic strategies, an OTC oral glutamatergic augmentation—dextromethorphan plus piracetam—was considered. The challenge lay in keeping dextromethorphan active with CYP2D6 inhibition without at the same time lengthening the action of lisdexamfetamine, a stimulant that depends in part on the same enzyme for clearance.To thread that needle, the patient started controlled-release paroxetine at a fraction of its usual dose (6.25 mg nightly) together with dextromethorphan 30 mg and piracetam 600 mg, all taken at bedtime. The micro-dose paroxetine was sufficient to slow dextromethorphan metabolism yet too small, and too late in the day, to meaningfully alter stimulant kinetics. Over the next 25 days her Patient Health Questionnaire score dropped from 21 to 11 and her Generalised Anxiety score from 14 to 11; she reconciled with her partner, resumed social plans, and reported no change in the onset or offset of the morning stimulant.This single case suggests that very low, night-time paroxetine can anchor glutamatergic augmentation for mood and anxiety relief while avoiding any alterations in lisdexamfetamine pharmacokinetics. The approach may widen the practical use of dextromethorphan-based regimens in patients who rely on stimulants for comorbid ADHD.