Early observations from pharmacokinetic studies in psychiatry paved the way for drug metabolism and molecular genetic studies that began to more clearly identify and characterize genetic mechanisms that may influence drug outcomes. As was the case with many other therapeutic areas, differences in drug metabolism were initially identified. In the mid-1970s, Smith et al. studied response to the antihypertensive drug debrisoquine11 and observed that subjects’ drug responses could be separated into two distinct populations, extensive metabolizers and nonmetabolizers. The drug concentrations exhibited a binomial distribution, and since this discovery, debrisoquine has commonly been used as a probe drug for predicting cytochrome P450 (CYP) 2D6 enzyme activity. Subsequently, a number of research groups have investigated gene variants related to the pharmacodynamics of neuropsychiatric medications. Examples include serotonin2A receptor (HTR2A) and dopamine2 receptor (DRD2) variants related to antipsychotic response12 and serotonin transporter and antidepressant response,13 as well as others outlined in a recently published review by the European Group for the Study of Resistant Depression (GSRD).14 Similar studies were conducted to investigate adverse effects, where an association between a common serotonin transporter
