Clinical utility of drug measurement and pharmacokinetics: therapeutic drug monitoring in psychiatry

Abstract

Based on the assumption that a relationship between blood levels and clinical effects (therapeutic effects, adverse events and toxicity) can be defined and considering that after equal doses plasma concentrations vary markedly between individual patients, therapeutic drug monitoring (TDM) can assist to personalize dose adjustment. Taken together, drug levels and a knowledge of the pharmacological profile of the administered drugs can enable the optimal dosage to be tailored according to the need of the individual patient. Therapeutic drug monitoring has been established for a limited number of drugs. In psychiatry, it has a 40-year-long history, which started with nortriptyline. Evidence has accumulated which shows that TDM is a valid tool for the optimization of psychopharmacotherapy. When used adequately, TDM is helpful for many patients and in many situations. Combined with pharmacogenetic tests, the metabolic status of a patient can be well characterized. Several new observations have been made during routine TDM that have stimulated clinical pharmacological research, such as investigations on inherited differences in drug metabolism that are closely linked to TDM in psychiatry. The contributions of individual forms of cytochrome P450 (CYP) to the metabolism of drugs was elicited by clinical observations on pharmacokinetic drug interactions. Therapeutic drug monitoring requires a close collaboration between the prescribing physician, the laboratory specialist, the clinical pharmacologist and the patient. This complexity may result in errors which can be detected by analysing the appropriate use of TDM in clinical practice. More education has to be provided to the prescribing clinicians on the pharmacology of the drugs and the algorithm of TDM. Moreover, clinical trials should include measurements of blood concentrations during drug development to generate valid data on the relationships between drug concentrations and clinical outcomes under well-controlled conditions. This would merely increase the amount of work and costs, as high-throughput methods are now available in many laboratories. Any progress in TDM has direct benefits for the treatment of many individual patients.