receiving TCAs were concordant for response. Around the same period, Alexanderson et al. investigated steady-state plasma concentrations of nortriptyline in twins and postulated that the variability observed in the data could be due to genetic differences in ability to metabolize the drug.9 In 1994, O’Reilly et al. described eight family members diagnosed with depression who showed a similar pattern of response to tranylcypromine and lack of response to TCAs or various new-generation agents.10 Even though at that time the biochemical mechanisms of familial response were unknown, genetic variations in the metabolism of antidepressants were suspected. These hereditary studies provided the first evidence that genetic factors may account for some of the variability seen in drug response among patients with psychiatric conditions.
