At the age of 47, Jordan suffered his first severe depressive episode with psychotic symptoms and was admitted to a psychiatric state hospital. He was subsequently prescribed the tricyclic antidepressant clomipramine. During the first week of treatment, the dose of clomipramine was increased from 225 to 300 mg/day.
About 1 week after starting clomipramine, Jordan suffered side effects, including excessive sweating, an abnormally fast heart rate, low blood pressure, dizziness and constipation. Tests found that he had unusually high levels of certain liver enzymes and that he had higher than recommended concentrations of both drugs in his blood serum. Just over 2 months after admission to the hospital, doctors decreased his dose of clomipramine from 300 mg/day to 150 mg/day. Nine days later, the drug concentrations were still markedly increased. By the time the drug doses were decreased, the man’s depressive and psychotic symptoms had already greatly improved. All his side effects went away.
A pharmacogenetic test revealed that Jordan was a poor metabolizer of clomipramine, meaning that he had a reduced metabolism of clomipramine to less active metabolites. This can result in higher concentrations of the drug, which can increase the risk of side effects.
John’s poor metabolizer status along with the high dose of clomipramine resulted in the side effects he experienced.
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PharmGKB. Dutch Pharmacogenetics Working Group Guideline for clomipramine and CYP2D6. https://www.pharmgkb.org/guideline/PA166104964. Accessed October, 2013.
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