Clinical implications of 2-hydroxydesipramine plasma concentrations

The clinical utility of 2-hydroxydesipramine (2-OH-DMI) measurements was evaluated by examining the relationship of 2-OH-DMI concentrations in plasma to clinical outcome and side effects in depressed inpatients treated with desipramine (DMI). Studies were performed in responders and nonresponders to treatment and in patients experiencing subjective side effects or major adverse reactions necessitating interruption of treatment. Unlike DMI concentrations, 2-OH-DMI concentrations did not correlate with response. Summing the concentrations of parent drug and metabolite (DMI + 2-OH-DMI) did not improve the correlation over that achieved with DMI alone. Neither DMI, 2-OH-DMI, nor their sum correlated with subjective side effect totals or major adverse reactions. While our data do not permit any conclusions regarding the clinical activity of 2-OH-DMI, they suggest that its routine measurement in plasma is not likely to be useful in the management of depression.