Dosage regimen design for cyclic antidepressants: a review of pharmacokinetic methods

One of the difficulties in pharmacotherapy of depression is the frequent need to make several dosage titrations before reaching the optimal therapeutic dosage. This problem has led to several experimental approaches for predicting a stable antidepressant maintenance dose from plasma concentration data collected shortly following a test dose. The theoretical basis for these methods is reviewed along with the results of clinical trials. It is concluded that accurate steady-state concentrations of cyclic antidepressants can be predicted from kinetic analysis of plasma concentrations obtained early in therapy. The most applicable drug for prospective dosing methods is nortriptyline with its widely accepted therapeutic plasma concentration range. Other drugs that also have substantial evidence for predicting the optimal dose from an early point in therapy include desipramine and imipramine. Predictive dosing methods are easily applied in the inpatient setting. Multiple data points obtained between 12 and 48 hours after the first dose are likely to give accurate predictions and provide clinically useful information. More widespread application of predictive approaches to dosage regimen design of antidepressant pharmacotherapy may lead to reduced hospitalization and cost savings.