Point-of-care companion diagnostic tests for personalizing psychiatric medications: fulfilling an unmet clinical need

Over the last decade stable isotope-labeled substrates have been used as probes for rapid, point-of-care, non-invasive and user-friendly phenotype breath tests to evaluate activity of drug metabolizing enzymes. These diagnostic breath tests can potentially be used as companion diagnostics by physicians to personalize medications, especially psychiatric drugs with narrow therapeutic windows, to monitor the progress of disease severity, medication efficacy and to study in vivo the pharmacokinetics of xenobiotics. Several genotype tests have been approved by the FDA over the last 15 years for both cytochrome P450 2D6 and 2C19 enzymes, however they have not been cleared for use in personalizing medications since they fall woefully short in identifying all non-responders to drugs, especially for the CYP450 enzymes. CYP2D6 and CYP2C19 are among the most extensively studied drug metabolizing enzymes, involved in the metabolism of approximately 30% of FDA-approved drugs in clinical use, associated with large individual differences in medication efficacy or tolerability essentially due to phenoconversion. The development and commercialization via FDA approval of the non-invasive, rapid (<60 min), in vivo, phenotype diagnostic breath tests to evaluate polymorphic CYP2D6 and CYP2C19 enzyme activity by measuring exhaled ¹³CO₂ as a biomarker in breath will effectively resolve the currently unmet clinical need for individualized psychiatric drug therapy. Clinicians could personalize treatment options for patients based on the CYP2D6 and CYP2C19 phenotype by selecting the optimal medication at the right initial and subsequent maintenance dose for the desired clinical outcome (i.e. greatest efficacy and minimal side effects).