Desipramine Toxicity With Terbinafine

Mr. A, a 52-year old man with recurrent major depression of moderate severity and a baseline score of 27 on the Hamilton Depression Rating Scale 17-item version, responded to treatment with desipramine over a period of 2 months. In subsequent continuation treatment he remained stable while taking 350 mg/day with a serum level of 166 ng/ml (therapeutic range=125–250 ng/ml).

His primary care physician then started treating Mr. A with terbinafine for onychomycosis (a fungal nail infection). After 2 weeks of treatment, Mr. A began to notice increasing dizziness, which progressed to ataxia, incoordination, and difficulty swallowing. There were no specific cardiac-type symptoms, such as syncope or palpitations. In light of these new symptoms (after 3 weeks of treatment with terbinafine), Mr. A’s desipramine level was rechecked and was found to be 580 ng/ml, even though his desipramine dose had remained unchanged.

Mr. A stopped taking desipramine for several days; after resolution of his somatic symptoms he was restarted on a dose of 50 mg/day. While Mr. A was taking 50 mg/day, his desipramine level was measured and found to be 174 ng/ml. Mr. A continued taking terbinafine during this time. When terbinafine was ultimately discontinued a couple of weeks later, his desipramine level was found to have fallen to 21 ng/ml, while he was taking the same 50-mg/day dose. The dose was gradually titrated back up to the initial amount of 350 mg/day of desipramine, which produced a serum level of 152 ng/ml.