High plasma nortriptyline levels in the treatment of depression. I

Abstract

Following a 3-day single-dose kinetic study, 21 moderate to severely depressed inpatients were treated with 100 mg of nortriptyline nightly. Eighteen patients completed the 4-wk trial. The severity of depression was measured by weekly Hamilton Rating Scale and global rating. Blood for plasma nortriptyline estimation was taken at weekly intervals 12 hr following the nighttime dose. There was a 610ld variation in mean plasma nortriptyline levels, ranging from 120 µg/L to 681 µg/L. Patients with high plasma levels (<200 µg/L) showed significantly poorer clinical responses than those with levels below this limit. This study provides very strong support for the view that, in routine treatment, high plasma nortriptyline levels are significantly less effective than intermediate levels. Single-dose pharmacokinetic data obtained on the same patients showed a highly significant correlation with mean steady-state plasma levels obtained, which themselves correlated with clinical response. The value of predicting high plasma nortriptyline levels which are associated with poor response is discussed.