Dextromethorphan-induced near-fatal suicide attempt in a slow metabolizer at cytochrome P450 2D6

Dextromethorphan (DXM) is a common ingredient in several prescriptions and over-the-counter cough preparations. Its metabolism in humans includes hepatic O- and N-demethylation to form dextrorphan and 3-methoxymorphinan, respectively, followed by conjugation. The active metabolite dextrorphan is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been linked with psychosis, especially in rapid metabolizers at cytochrome P450 (CYP) 2D6.

The patient was a 66-year-old married, retired Portuguese American male, with no prior psychiatric history. He presented to the emergency department following a brief psychotic episode leading to a near-fatal suicide attempt after ingesting an excessive quantity of DXM. The patient had started by ingesting 3 tablespoons (45 mL) of cough syrup per day (total, 1575 mg/d) instead of the prescribed 3 teaspoons (15 mL). In the days preceding the admission, his frequency of use had increased substantially (up to 6 times per day). During the treatment of this episode, he was initially started on sertraline 50 mg/d, which was discontinued within 48 hours, given the lack of depressive symptoms, and risperidone was initiated at 1 mg BID. The medication was discontinued after several months, and the patient completely recovered. Possible medical and psychiatric etiologies related to this brief psychotic episode in a geriatric patient are also discussed.

Caution should be exercised in prescribing DXM to geriatric patients, as they may be more susceptible to the drug's adverse effects because of increased clearance time. It appears that dose may play a greater role in causing psychosis, rather than the rate of metabolism, as evident in our patient who, contrary to the more often described scenario, was a slow metabolizer at CYP2D6.