A New Intervention for Implementation of Pharmacogenetics in Psychiatry: A Description of the PSY-PGx Clinical Study

<b>(1) Background</b> Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. <b>(2) Methods</b> This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants <i>escitalopram</i> and <i>sertraline</i> or antipsychotics <i>risperidone</i> and <i>aripiprazole</i> according to the latest state-of-the-art international dosing recommendations for <i>CYP2C19</i> and <i>CYP2D6</i> metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. <b>(3) Conclusions</b> This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.