Medication exposure is dependent upon many factors, the single most important being if the patient took the prescribed medication as indicated. To assess medication exposure for psychotropic and other medication classes, we enrolled 115 highly adherent psychiatry patients prescribed five or more medications. In these patients, we measured 21 psychotropic and 38 non-psychotropic medications comprising a 59-medication multiplex assay panel. Strict enrollment criteria and reconciliation of the electronic health record medication list prior to study initiation produced a patient cohort that was compliant with 91% of their prescribed medications as determined by comparing medications detected empirically in blood to the electronic health record medication list. In addition, 13% of detected medications were not in the electronic health record medication list. We found that only 45% of detected medications were within the literature-derived therapeutic reference range, with 40% below and 15% above the reference range specific to each medication. When psychotropic medications were analyzed at trough-level, only sertraline was found to be within the therapeutic reference range for all patients tested. Concentrations of the remaining medications indicated extensive sub-therapeutic exposure. This is the first study to empirically and comprehensively assess medication exposure obtained in highly compliant, co-morbid patients, minimizing the important behavioral factor of adherence known to drive erratic medication exposure. These data indicate that sub-therapeutic exposure is extensive and must be considered when therapeutic issues arise, such as treatment resistance in psychotherapy.

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