Why is therapeutic drug monitoring helpful?
Since the 1970s, the therapeutic drug monitoring (TDM) assay has been used to help monitor and maintain drug levels within a specific therapeutic range . The therapeutic range is the concentration range in which a drug exerts its clinical effect with minimal adverse effects for most patients .
For some drugs, maintaining this steady state can be difficult, because each person absorbs, metabolizes, utilizes and eliminates drugs differently. Additionally, therapeutic drug-monitoring rates may change over time depending on disease states and interactions with other medications.
TDM can also assist in determining the patient’s non-adherence or partial adherence (e.g. when the medication is not taken as prescribed), and the effect of drug interactions, which may cause higher or lower than expected drug concentrations at a given dosage . In short, drug monitoring helps personalize a dose to fit the specific needs of the patient.
Although TDM has become the standard of care in psychiatry for lithium as a result of the narrow therapeutic range , it is not as well established for other antipsychotic medications.
The Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology  were released to offer a tool for optimizing pharmacotherapy. Although there are enormous medical and economic benefits of prescribing drugs to treat psychiatric patients, therapeutic outcomes can be unsatisfactory.
The guidelines recommend regular monitoring of antipsychotic drug concentrations in the blood at least every 3–6 months as a means to prevent relapses and re-hospitalizations. In cases where non-adherence is suspected or where the patient is prescribed co-medications that might affect the pharmacokinetics of a prescribed drug, the frequency of TDM requests may be increased . TDM is also valuable when medication is switched from oral to LAI formulations, or vice versa .
What is the intended use of antipsychotic assays and what do the TDM assays measure?
Antipsychotic assays measure the concentration of an antipsychotic drug in the patient’s blood.
If the dose of medication is known (dose in milligrams, dosing frequency per day, and time since last dose), antipsychotic assays provide a quantitative result which may then be referenced against the patient’s baseline and may also identify if the result is within expected range for that dose regime [8,9].
Measured concentrations for adherent patients at steady state are expected to be in the measuring range of the assays. If the medication or dose of medication is unknown (e.g. in an emergency department), antipsychotic assays are still able to identify and measure the prescribed antipsychotic drug.
The therapeutic reference range is a population-based range defined in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology. The ranges are based on studies to determine blood levels below which clinical response is less likely and calculations for blood levels expected on the highest recommended dose .
The usefulness of TDM varies depending on the clinical situation and the particular drug involved. As a result, four levels of recommendation are defined, ranging from ‘strongly recommended’ to ‘potentially useful’ as follows :
Level 1: strongly recommended
Level 2: recommended
Level 3: useful
Level 4: potentially useful.
Of the second-generation antipsychotic drugs, clozapine and olanzapine have been classified as Level 1 – TDM strongly recommended, owing to its beneficial effect in investigating decreased tolerability or intoxication. Aripiprazole, quetiapine, risperidone and paliperidone, however, are set at Level 2 – TDM Recommended, as it can assist where there are special indications or when problem solving is necessary .
What technologies are available for antipsychotic drug testing?
Technologies for testing antipsychotic drugs can be laboratory based or via point-of-care testing (POCT).
POCT can be done rapidly and be performed by clinical personnel in the presence of the patient. These rapid test results can provide a physician with answers that can quickly help determine a course of action or treatment. Although they can deliver the result quickly, they can be prone to pre-analytical and post-analytical error and they can be a burden to busy clinical staff.
Testing within the core laboratory is performed by highly trained scientific staff. Stringent quality procedures throughout every stage of sample processing ensure the quality and accuracy of a test result.
Today, the most widely used methodology for TDM of antipsychotics is liquid chromatography-tandem mass spectrometry owing to its sensitivity and specificity towards the identification of analytes. This technique requires highly skilled staff and is time consuming, which can lead to longer turnaround times for results.
The guidelines indicate that for an effective TDM service, the availability of accurate analytical methods that produce results within a reasonable time are essential. In cases of suspected intoxications, TDM methods should allow drug analysis within 1–2 hours .
Responding to this need Beckman Coulter, in partnership with Saladax Biomedical Inc., has recently introduced a laboratory-based nanoparticle homogeneous agglutination technology to provide rapid, high-quality assays to measure the antipsychotic drugs listed in Table 1.