2-Hydroxydesipramine and desipramine plasma levels and electrocardiographic effects in depressed younger adults.

Desipramine was given to 34 outpatients aged 20 to 51 years who had primary major depressive disorder but who were otherwise in good health. Daily dosage at bedtime was constant for the final 3 weeks of the 5-week study (mean, [SD] 169.1 [46.1] mg). Electrocardiograms done predrug and after 5 weeks were read by a cardiologist blind to the order in which they were performed. Plasma samples drawn 14 hours after the final study dose were assayed by high performance liquid chromatography; mean (SD) levels were 140.2 (140.0) ng/ml for desipramine and 56.5 (29.4) ng/ml for 2-hydroxydesipramine (2-OH-DMI). Heart rate and PR, QRS and QTc intervals were significantly greater at the end of the study than at baseline, while QT intervals were significantly less. Changes in heart rate and PR, QT and QTc intervals were significantly negatively correlated with the value of the respective cardiac parameters at baseline. Changes in PR interval were significantly positively correlated with log desipramine, log 2-OH-DMI and log (desipramine + 2-OH-DMI). Stepwise multiple regression analyses showed that, for PR interval, each of the three plasma level variables showed a significant ability to improve R2 over that obtained from baseline PR alone. These findings suggest that both 2-OH-DMI and desipramine plasma levels predict a prolongation of intracardiac conduction in younger adults and that monitoring both levels may be useful in the clinical management of certain younger adult patients.