After experiencing 2 months of depression, anxiety, insomnia and delusions, John – a 54-year-old man- attempted suicide and was subsequently hospitalized. He was diagnosed with major depression with psychotic symptoms. In addition to undergoing psychotherapy, he was prescribed the tricyclic antidepressant nortriptyline. The patient’s dose of nortriptyline was increased gradually from 50 mg/day to 100 mg/day. Although he had a somewhat higher than recommended plasma concentration of nortriptyline, the man’s dosage was further increased over 20 days to 150 mg/day in order to advance his improvement. This led to an even greater rise in the drug’s plasma concentration. The man experienced side effects of dry mouth, constipation and dizziness. Because of these side effects and the high drug concentration, the dose was decreased to 100 mg/day. The plasma level decreased but was still over the recommended range. After being hospitalized for 1 month, the patient was discharged and continued taking 100 mg/day.
Through a pharmacogenetic test, John was determined to be a poor responder to nortriptyline. He couldn’t clear the drug out of his system, leaving him at risk of side effects due to a higher plasma concentration of the drug.
Hicks, J. K. et al. (2013) Clinical pharmacogenetics implementation consortium guidelines for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 93, 402-8.
Lee, S.-Y. et al. (2004) A case report of a poor metabolizer of CYP2D6 presented with unusual responses to nortriptyline medication. J Korean Med Sci 19, 750-2.
PharmGKB. Dutch Pharmacogenetics Working Group Guideline for nortriptyline and CYP2D6. https://www.pharmgkb.org/drug/PA450657. Accessed September, 2013.