For these reasons, therapeutic drug monitoring (TDM), the measurement of drug levels directly affecting clinical decision making, has the potential to add great value in the management of patients with schizophrenia and other disorders for which these medicines are utilized. Although TDM is routine practice in some areas of psychiatry, particularly in the management of mood stabilizers, its adoption into the management of antipsychotic drugs has been slow. This state of affairs persists despite a fairly large body of literature supporting the use of TDM with antipsychotics and, as of 2011, the establishment of consensus guidelines regarding monitoring parameters.2
The drug concentration in the blood will depend on absorption, distribution and elimination of the drug, and will continuously mirror the fate of the drug in various tissues and organs. The basic assumptions underlying TDM are that drug metabolism, as well as other factors that affect the drugs pharmacokinetics, varies from one patient to another and that the blood level of a drug is more closely related to the drug’s therapeutic effect or toxicity than is the dosage. TDM comprises the assessment and communication of drug levels in blood as well as recommendations for dose adjustments. TDM is by tradition based on concentration intervals (therapeutic range or index) within which most subjects are expected to have their optimal response (high enough to give the desired effect but low enough to avoid toxicity).
Recommended dosing regimens are designed to generate blood concentrations within a therapeutic range. Therapeutic ranges, however, are only intermediate endpoints that must be used in the context of additional criteria to assess the clinical efficacy and tolerability of any given drug therapy. The therapeutic goal must be individualized.3 Although routine drug monitoring may not be necessary in patients who are clinically stable and not experiencing adverse effects, major clinical decisions, including the decision to increase doses or switch medications due to lack of efficacy should be informed by serum concentrations of the drugs in question. Concerns about potential non-adherence or treatment-emergent adverse affects can also be clarified through direct monitoring of drug levels. The experience with clozapine should serve as an example of the potential utility of TDM.4
It is hoped that increased utilization of these measurement strategies can help us to achieve the goals of more personalized medicine with better, more timely and more cost effective outcomes.
- Guo T, et al. Measurement-Based Care Versus Standard Care for Major Depression: A Randomized Controlled Trial With Blind Raters. Am J Psychiatry. 2015; 172:1004–1013.
- Hiemke C, et al. Agnp consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry. 2011; 44(6):195-235.
- Lopez LV, Kane JM. Plasma levels of second-generation antipsychotics and clinical response in acute psychosis: A review of the literature. Schizophrenia Research. 2013; 147(2-3):368-374.
- Olsso E, et al. Genetic and Clinical Factors Affecting Plasma Clozapine Concentration. Prim Care Companion CNS Disord. 2015; 17(1):10.4088/PCC.14m01704.