Rates of in vivo methylation of desipramine and nortriptyline.

Routine monitoring of an 81-year-old man receiving treatment with nortriptyline for generalized anxiety disorder and depression revealed plasma concentrations of both amitriptyline and nortriptyline. In humans, the tricyclic antidepressant (TCA) tertiary amines imipramine and amitriptyline are typically metabolized by demethylation to the secondary active metabolites desipramine and nortriptyline, respectively. However, to our knowledge, methylation of secondary amine TCAs has been reported in only one case report of nortriptyline overdose and in two studies involving desipramine.