Bio-Rad - Preparing for a Stress-free QC Audit

Insight into therapeutic drug monitoring of antipsychotic medication

According to the World Health Organization, almost 15% of the world’s population is living with mental illness. We have medications that can be effective, but outcomes can vary. We caught up with Heather Read-Harper (Beckman Coulter) to find out more about the value of therapeutic drug monitoring in treating mental health disorders.

How common are schizophrenia and bipolar disorder and how are these conditions diagnosed?

Everyone has mental health, the World Health Organization (WHO) famously says, “There is no health without mental health.” It is defined as our emotional and psychological wellbeing and is influenced by our life experiences and implies the absence of an illness or disorder.

Mental illness or mental distress are different to mental health and refer to a wide range of disorders that affect mood, thinking and behaviour. Mental distress or low mental health can impact an individual when experiencing situations where emotions, thoughts and feelings can be overwhelming. In most cases, this can be overcome by practising self-care techniques and mindfulness.

Mental illness is a general term for a group of medically defined conditions such as mood disorders (depression or bipolar disorder), anxiety disorders, personality disorders and psychotic disorders (such as schizophrenia). These conditions can vary in degree of severity, ranging from mild to moderate to serious. Serious mental illness (SMI) is defined as a mental, behavioural, or emotional disorder resulting in serious functional impairment, which substantially interferes with or limits one or more major life activities. The burden of mental illnesses is particularly concentrated among those who experience disability due to SMI [1].

The WHO World mental health report published in June 2022 indicates that in 2019, 13% of the global population is living with mental disorders. Of these, schizophrenia, which occurs in 24 million, is a primary concern and bipolar disorder, another key concern of mental health services around the world, occurs in 40 million people [2].

Bipolar disorder causes an individual’s mood to change from manic highs to extreme lows of depression, sometimes lasting for long periods. Symptoms include feeling sad, hopeless, or irritable most of the time, lacking energy, difficulty concentrating and remembering things, loss of interest in everyday activities, feelings of emptiness or worthlessness, feelings of guilt and despair, feeling pessimistic about everything, self-doubt.

Schizophrenia is a severe long-term mental health condition. It causes a range of different psychological symptoms and affects the way a person will think and cope with daily life. Someone living with schizophrenia may experience hallucinations, delusions, disorganized thinking and lack motivation for daily activities.

Mental illnesses are recognizable conditions that can be professionally diagnosed and treated, although scientists have yet to discover any genetic markers, chemical imbalances or other differences in brain function which reliably predict or identify mental illness [3].

Therefore, diagnosis relies on a mental health assessment. The first step is to see a primary care doctor who will make an initial assessment by asking questions about mood, thoughts and behaviours, lifestyle and any recent events that might affect wellbeing. A physical examination along with lab tests might also be necessary to check for related complications. For less common problems or suspicion of SMI, a referral to a mental health specialist, such as a psychiatrist, will be necessary. After assessing your condition, a psychiatrist may prescribe medication or recommend other treatments, such as counselling or cognitive behavioural therapy.

There are many medications prescribed for mental illness, these include antidepressants, antipsychotics, benzodiazepines and mood stabilizers. For the management of SMI, such as schizophrenia and bipolar disorder, antipsychotics are commonly prescribed orally or as a long-acting injectable (LAI).

There are two generations of antipsychotic medication. Both the older first-generation or ‘typical’ antipsychotics and newer second-generation ‘atypical’ antipsychotics can be prescribed to effectively reduce psychotic symptoms and improve overall quality of life. However, second-generation antipsychotics are associated with a lower risk of neurological symptoms, than first-generation drugs.

Antipsychotics can affect people differently because of treatment resistance, poor tolerability or interactions with other medication. Drug type or dosage may need to be adjusted accordingly.

Beckman AssaysControlsCalibrators1 scaled e1680866422998

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 [4]. The therapeutic range is the concentration range in which a drug exerts its clinical effect with minimal adverse effects for most patients [5].

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 [6]. 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 [3], it is not as well established for other antipsychotic medications.

The Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology [8] 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 [3]. TDM is also valuable when medication is switched from oral to LAI formulations, or vice versa [7].

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 [8].

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 [8]:
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 [8].

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 [8].

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.

Schermafbeelding 2022 11 08 om 20.12.09

Table 1. Analytes measured by assays for monitoring levels of antipsychotic medication

These assays deliver results that correlate to established methods and can be seamlessly integrated into routine chemistry testing on Beckman Coulter’s scalable AU clinical chemistry analysers. With no sample pre-treatment, ready to use reagents and random-access testing, turnaround time for patient test results are shortened to minutes instead of days – to better manage and monitor treatments for psychiatric patients.

The interviewee

Heather Read-Harper,
Senior European Marketing Manager for Immunoassay
and Clinical Chemistry of Beckman Coulter
Beckman Coulter United Kingdom Limited,
High Wycombe, Buckinghamshire, UK

For further information visit Beckman Coulter


1. National Institute of Mental Health (
2. World mental health report: transforming mental health for all. World Health Organization 2022 (
3. A short guide to psychiatric diagnosis. Mental Health Europe 2018 (
4. Touw DJ, Neef C, Thomson AH et al. Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 2005;27:10–17.
5. Birkett DJ. Therapeutic drug monitoring. Aust Prescr 1997;20:9–11 (
6. Tange SM, Grey VL, Senécal PE. Therapeutic drug monitoring in pediatrics: a need for improvement. J Clin Pharmacol 1994;34(3):200–214.
7. Patil P, Schwartz TL. Fine tuning the use of second generation antipsychotics. J Ment Health Clin Psychol 2018;2(5):22–39
8. Hiemke C, Bergemann N, Clement HW et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: update 2017. Pharmacopsychiatry 2018;51(01/02):9–62 (
9. Horvitz-Lennon M, Predmore Z, Mattke S. Personalizing antipsychotic treatment of schizophrenia: monitoring plasma levels for improved treatment decisions. RAND Corporation 2017 (