Antipsychotics have numerous evidence-based uses in the twenty-first century, including schizophrenia spectrum and other psychotic disorders, bipolar disorder, unipolar major depression, behavioral disturbances of autism, tic disorders, and obsessive compulsive disorder . The application of antipsychotic therapy in many of these conditions is adjunctive, and it may be withdrawn during less active phases of the illness. For patients with schizophrenia spectrum disorders, antipsychotics are the foundation of treatment without which the patient is at risk for relapse, and the attendant psychiatric, social, and legal consequences [2, 3]. Given the level of disability often encountered with the onset of illness, the care and management of individuals with schizophrenia exerts a significant economic toll on society [4–6]; moreover, this burden accrues most directly to families and direct caregivers in the form of financial loss compounded by stress and decreased quality of life [7, 8]. Of particular concern are the disproportionate direct and indirect costs associated with treatment-resistant schizophrenia (TRS)  (see Figure 0.1).
Healthcare costs per patient-year for schizophrenia patients from studies published 1996–2012 worldwide, for US schizophrenia patients, and for treatment-resistant schizophrenia patients (2012 USD)
(Adapted from: J. L. Kennedy, C. A. Altar, D. L. Taylor, et al. . The social and economic burden of treatment-resistant schizophrenia: A systematic literature review. Int Clin Psychopharmacol, 29, 63–76.)
That the care costs for TRS are 3–11 times higher than for other schizophrenia patients is not surprising, but the disturbing clinical reality is that, aside from treatment resistance, there are many reasons patients fail to respond adequately to an antipsychotic, with nonadherence, underdosing, and kinetic issues playing significant roles . To emphasize this point, a study of 99 schizophrenia patients deemed treatment resistant in the South London and Maudsley National Health Service (NHS) foundation clinic found that 35% had subtherapeutic plasma antipsychotic levels . Real-world data such as these encapsulate the basic arguments for monitoring of antipsychotic plasma levels: antipsychotic nonadherence is common in schizophrenia patients ; clinicians are poor estimators of medication nonadherence [12–14]; kinetic variations or underdosing contribute to inadequate response ; plasma level, and not prescribed dose, is the best proxy for central nervous system antipsychotic effects [15, 16].