Patients receiving tricyclic antidepressants exhibit extreme variability in steady-state plasma concentrations because of differences in metabolism. At routine dosages, rapid metabolizers may have suboptimal concentrations while slow metabolizers can suffer from adverse effects due to inappropriately high concentrations. Neither may benefit from the drug therapy. Through analysis of plasma levels of tricyclic antidepressants, an optimal therapeutic response can be achieved, and the risk of serious side effects can be reduced.