Bupropion plasma concentration and antidepressant response in elderly patients: A prospective, randomized, double-blind study

Several studies in mid-life adults have suggested a curvilinear relationship between bupropion plasma concentration and antidepressant response. Similarly, elevated levels of bupropion's major metabolites have been associated with reduced antidepressant response and increased side effects. These studies have been limited by use of ascending dose designs. We conducted a prospective, randomized, double-blind, fixed-dose study of bupropion treatment in 15 elderly subjects diagnosed with major depression. Concentration of bupropion and hydroxybupropion (HB), erythrobupropion (EB), and threobupropion (TB) were determined by high performance liquid chromatography. We found bupropion plasma concentrations less than 30 ng/ml predicted antidepressant response. Poor antidepressant response was associated with elevated levels of EB and TB, but not HB. Total metabolite concentration (HB+EB+TB) was also correlated with severity of adverse side effects. Therapeutic drug monitoring may offer advantages when treating older individuals with bupropion, with optimal antidepressant response at bupropion plasma concentrations less than 30 ng/ml.