A recent study carried out in Sweden found that volumetric dried blood spot testing holds promise for lithium monitoring during the treatment of bipolar disorder. Lithium is among the most effective treatments within psychiatry, however safe usage requires regular patient monitoring. This is expensive and inconvenient for patients, which may lead to non-compliance and unsafe outcomes. A recent study from Sweden is the first to describe a home-sampling approach for lithium monitoring, and highlights the potential in using volumetric dried blood spots to save resources while improving compliance to make lithium treatment safer.
Therapeutic Monitoring of Lithium
The therapeutic potential of lithium within psychiatry was discovered in the mid-1800s, and the first randomly-controlled trials for bipolar disorder were conducted about 100 years later. The U.S. Food and Drug Administration approved lithium as a treatment for bipolar disorder in 1970. Today, lithium is the most widely used treatment for bipolar disorder, and it is used off-label to treat certain forms of depression.
Although its mechanism of action is unknown, lithium is considered to be one of the most effective treatments for psychiatric conditions. Lithium is administered orally, and it has a narrow therapeutic range, which means that there is only a small difference between the minimum effective concentration and the minimum toxic concentration in the blood. Therefore, careful therapeutic drug monitoring must be undertaken regularly to ensure that lithium treatment is optimally effective and safe for patients.
The Drawbacks of Conventional Lithium Monitoring
Since the development of the Coleman flame photometer in 1958, measuring the concentration of lithium in patient serum has been the predominant approach to therapeutic monitoring, whereby the serum concentration is first measured and then adjusted to an optimal individual concentration. This method works by measuring the intensity of light emitted (measured using a wavelength of a certain colour) when an element, in this case lithium, is exposed to a flame.
Colorimetric assays to measure lithium in serum and plasma are also used in clinical labs, however background signal renders these assays unsuitable for whole blood, as well as serum and plasma samples derived from haemolytic blood samples (i.e. those that contain lysed red blood cells).
In standard clinical practice, patients receiving lithium treatment are routinely monitored via venous blood draw at least every three to six months. This method requires many resources, including the presence of a trained phlebotomist, and regular visits to healthcare facilities may also be inconvenient for patients. Moreover, in low-income settings, the infrastructure to monitor lithium may not be present at all, which makes lithium treatment unsafe and unfeasible in these areas.
Risk of non-compliance
The drawbacks with conventional lithium monitoring lead to risks of non-compliance and dangerous outcomes for patients, and warrant the exploration of new patient-centric approaches that are more cost-effective, less invasive and accessible to those in need regardless of geographical location.
Using Dried Blood Spot Testing for Lithium Monitoring
Although serum is the standard matrix used within lithium monitoring, lithium is also detectable in whole blood of treated individuals, albeit at lower concentrations than in serum. This observation prompted serval inconclusive investigations about whether the ratio of blood to serum lithium levels could be used as a relevant biomarker. However, few studies have explored the possibility of monitoring lithium in whole blood.
In January 2023, researchers from various Swedish institutions including the Karolinska Institute, Stockholm Healthcare Services, Karolinska University Hospital, and KTH Royal Institute of Technology, reported a study that compared conventional lithium monitoring in serum from venous blood with volumetric dried blood spots (DBS) collected using our quantitative DBS device Capitainer®B.
Strong Correlation Between Lithium Levels Measured in DBS Samples Collected with Capitainer®B and Venous Blood Samples
For the study, finger-prick blood and venous blood samples were collected from 39 patients receiving lithium treatment for a psychiatric disorder at the time of sampling. To ensure a wide range of lithium concentrations across the samples, time since most recent dose was not considered when sampling.
Finger-prick samples were applied to Capitainer®B, while venous blood samples were processed for standard lithium measurement with flame emission photometry.
The findings of that study, published in Journal of Pharmaceutical and Biomedical Analysis, demonstrate a strong linear correlation between lithium concentrations in DBS samples and whole blood (1). The authors note that the linear correlation observed (r2 = 0.90) is an improvement on a study by others in the field from 2020 that measured lithium in dried blood spots, and that this is likely due to the use of the volumetric Capitainer®B device, which exhibited the best precision among evaluated microsamplinmg devices in a recent study from the UK (2).
The study by Wikström et al. is the first to investigate and demonstrate the potential of a volumetric microsampling device in therapeutic blood monitoring of lithium.
In clinical practice, lithium concentrations are monitored 12 hours after the most recent dose, and the use of other medications is also taken into account. The authors note that further experiments
that account for these factors will strengthen their findings.
Dried Blood Spots Offer a Patient-Centric Approach to Lithium Monitoring
According to drug usage statistics from the U.S., an estimated 400,000 people are receiving lithium treatment every year in the U.S. alone. For effective and safe treatment, all of these patients are required to attend a healthcare facility at least several times per year for lithium monitoring.
Given the negative effects of bipolar disorder and depression on social and personal functioning, especially in severe cases, the option to perform non-invasive self-sampling in the comfort of one’s home would remove the burden and expense of regular travel, and ultimately improve the quality of life in this patient group.
Furthermore, home sampling without the need for a trained phlebotomist also would also facilitate lithium monitoring in remote or low-resource areas, since DBS samples can be shipped as non-hazardous material at ambient temperature to suitable testing laboratories.
The findings of Wikström et al. highlight for the first time the potential of using a volumetric mcrosampling device such as Capitainer®B to develop a patient-centric solution for lithium montoing, and raise hopes for safer and more accessible treatment with one of the most effective drugs in psychiatry.
- Wikström F, Olsson C, Palm B, Roxhed N, Backlund L, Schalling M, Beck O. (2023). Determination of lithium concentration in capillary blood using volumetric dried blood spots. J Pharm Biomed Anal. 227(115269), doi: 10.1016/j.jpba.2023.115269.
- Carling RS, Emmett EC, Moat SJ. (2022). Evaluation of volumetric blood collection devices for the measurement of phenylalanine and tyrosine to monitor patients with phenylketonuria. Clin Chim Acta. 535(157-166), doi: 10.1016/j.cca.2022.08.005.
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Global CRO Altasciences Evaluates Capitainer®qDBS Microsampling. In 2022, Altasciences, a contract research organisation working with pharmaceutical companies in drug development, tested Capitainer®B for the quantification of a panel of 15 anti-epileptic drugs, and found that the device delivered accurate and precise blood volumes, was straightforward to use, and was devoid of the limitations of conventional DBS.