Bipolar disorder (BD) is a chronic psychiatric illness characterized by recurrent manic and depressive episodes, leading to significant impairment. Lithium remains a key treatment for BD, particularly in relapse prevention. However, its narrow therapeutic range and inter-individual pharmacokinetic variability necessitate careful dosing. This study aims to establish a suitable platform to investigate the pharmacokinetics of lithium in hospitalized patients with BD in Mashhad, Iran, to optimize therapeutic use and minimize toxicity. This cross-sectional study was conducted at Ibn Sina Hospital, Mashhad, between 2016 and 2022. Hospitalized patients diagnosed with BD and receiving lithium therapy were included. Clinical, demographic, and laboratory data were collected, including lithium serum levels, renal function parameters, and co-administered medications. Advanced data pre-processing techniques were applied to ensure accuracy and facilitate future pharmacokinetic modeling. A total of 701 patients (53.1% male, mean age: 38.0 SD: ± 12.2 years) with 795 hospitalization episodes were analyzed. The mean lithium serum concentration was 0.65 ± 0.30 mEq/L. Thyroid disorders (5.9%) and diabetes (5.6%) were the most common comorbidities. The mean duration of hospitalization during lithium treatment was 21.7 ± 10.8 days. Sodium valproate was the most frequently co-prescribed medication (n = 553), followed by lorazepam (n = 468) and risperidone (n = 458). Lithium dosing showed considerable variability, emphasizing the need for individualized therapeutic strategies. This study provides valuable insights into lithium pharmacokinetics in Iranian BD patients. The findings highlight the necessity of personalized dosing approaches to enhance efficacy and reduce adverse effects. Future research should incorporate pharmacokinetic modeling and machine learning to refine lithium therapy.

Lithium is the first-line treatment for bipolar disorder. However, the narrow therapeutic window of serum (s-)lithium is near its toxicity range, necessitating continuous monitoring of patients, a process involving regular hospital visits. On-demand home sampling could allow for more frequent testing, possibly resulting in safer patient outcomes, further dosage optimization, and increased compliance. This article presents a device that measures the s-lithium concentration from whole blood. The device consists of a single-use cartridge able to conduct on-chip serum filtration, volume-metering and an on-chip colorimetric assay. Spiked whole blood shows good linearity (Pearson's r = 0.96, R2 = 0.92), a limit-of-detection of 0.3 mmol L-1, and an average deviation of 0.05 mmol L-1 (±6%) compared to atomic absorption spectroscopy. The on-chip colorimetric assay has shown to be a promising technique for measuring s-lithium concentration from whole blood and could allow patients to assess lithium levels at home and make the treatment available for new patient groups.

Bipolar disorder is a complex mental disorder that often requires long-term medication management. Lithium carbonate is widely used to prevent and treat the recurrence of bipolar disorder. However, even with normal serum lithium levels, some rare but serious side effects may occur. This case report describes a 42-year-old female patient with bipolar disorder who experienced "electrical shock-like" convulsions after taking lithium carbonate sustained-release tablets, despite having normal serum lithium concentrations. The patient had a history of emotional instability for 27 years, and no obvious psychotic symptoms such as hallucinations or delusions were found upon psychiatric examination at admission. On the 33rd day of medication, the patient began to experience frequent rapid convulsions in the head, neck, and upper body. Considering the possibility of drug side effects, lithium carbonate was discontinued, and the convulsions subsequently subsided. Electroencephalogram (EEG) examination showed no abnormalities. After 10 days of treatment, the convulsions had essentially disappeared. This case reminds clinicians that even with normal serum lithium levels, toxic symptoms may occur, and close monitoring of the patient's clinical manifestations and serum lithium levels is essential. Additionally, poor diet and reduced sodium intake may increase the risk of lithium toxicity, so these factors should also be taken into consideration.

Bipolar disorder (BD) is a severe mental illness characterized by significant mood swings. Effective drug treatment modalities are crucial for managing BD.

To analyze the current status and future trends of global research on BD drug treatment over the last decade.

The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment. A total of 2624 articles were extracted. Data visualization and analysis were conducted using CiteSpace, VOSviewer, Pajek, Scimago Graphica, and R-studio bibliometrix to identify research hotspots, key contributors, and future trends.

The United States, China, and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration networks. The University of Pittsburgh, Massachusetts General Hospital, and the University of Michigan have been identified as the major research institutions in this field. The Journal of Affective Disorders is the most influential journal. A keyword analysis revealed research hotspots related to clinical symptoms, drug efficacy, and genetic mechanisms. A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited paper.

This study provides a detailed overview of the field of BD drug treatment, highlighting key contributors, research hotspots, and future directions. The study findings can be employed as a reference for future research and policymaking, which may enable further development and optimization of BD pharmacotherapy.

Lithium exhibits a narrow margin between therapeutic doses and toxic blood concentrations, which can pose a substantial risk of toxic effects. Reportedly, lithium toxicity may be associated with a reduced anion gap; however, the precise relationship remains unclear. This study examined several different anion gap calculation methods to detect toxic lithium concentrations without directly measuring blood lithium concentrations.

Our retrospective study analyzed blood samples collected for lithium concentration measurements. The anion gap was determined using three different methods, both with and without albumin and lactate concentration corrections. Samples were categorized into two groups based on lithium concentration (<1.5 or ≥1.5 mmol/L), and anion gap values were compared. Correlation and logistic regression analyses were used to assess the relationship between each anion gap indicator and lithium concentration. Receiver operating characteristic curves were used for diagnostic analysis.

Overall, 24 measurements were collected, with 41.7% of samples falling within the toxic range. The high-lithium concentration group exhibited significantly smaller anion gaps. Correlation and logistic regression analyses revealed a significant association between anion gap values and lithium concentrations. Areas under the receiver operating characteristic curve were: conventional anion gap 0.77 (95% CI: 0.55-0.94); albumin-corrected anion gap 0.85 (95% CI: 0.66-1.00); and both albumin- and lactate-corrected anion gap 0.86 (95% CI: 0.66-1.00).

The anion gap is calculated as the difference between measured cations and anions. Accumulation of lithium (a cation) may decrease measured cations and decrease the calculated anion gap. Abnormal albumin and lactate concentrations may also alter the anion gap and affect its usefulness as a diagnostic marker for elevated serum lithium concentrations. A negative likelihood ratio of 0.1 suggests that the anion gap might be valuable in excluding toxicity.

The corrected anion gap, accounting for albumin and lactate concentrations, may be beneficial in suggesting the possibility of toxic lithium concentrations.

Bipolar disorder is commonly treated with lithium carbonate. The concentration of lithium in the blood serum should be closely monitored in patients who require long-term lithium therapy. To date, no colorimetric method of detecting lithium ions has been reported using nanosensors. We have developed a novel chemosensor based on nanozyme (NZ) to address this clinical need. The GO-Ag2O NZs were synthesized by a sonochemical method and used as a colorimetric nanosensor to detect lithium ions in human blood serum (Li (I)). To characterize NZs, various techniques were employed, including XRD, FTIR, TEM, FESEM, EDX, Raman spectroscopy, BET, DLS, Zeta potential, and ICP-OES. According to TEM and FESEM images of GO-Ag2O, the nanoparticles (NPs) of Ag2O are uniformly distributed on the surface of 2D graphene oxide sheets. In addition, silver oxide nanoparticles exhibited a cubic morphology with an average size of 3.5 nm. We have examined the performance of the NZs in an aqueous medium and in human blood serum that contains Li (I). A colorimetric test revealed that NZs synthesized in the presence of ultrasound were more sensitive to Li (I). According to the linearity of the calibration curves' ranges, Li (I) has a limit of detection (LOD) of 0.01 µg/mL. Furthermore, it displayed a linear range between 0 and 12 µg/mL. GO-Ag2O NZs showed noticeable color changes from green to orange after exposure to Li (I). An incubation time of two minutes was found to be the most effective for sensing. This innovative approach provides a reliable method for monitoring lithium levels and ensuring patient safety during long-term lithium therapy for bipolar disorder.

Psychiatric disorders often require pharmacological interventions to alleviate symptoms and improve quality of life. However, achieving an optimal therapeutic outcome is challenging due to several factors, including variability in the individual response, inter-individual differences in drug metabolism, and drug interactions in polytherapy. Therapeutic drug monitoring (TDM), by measuring drug concentrations in biological samples, represents a valuable tool to address these challenges, by tailoring medication regimens to each individual. This review analyzes the current landscape of TDM in psychiatric practice, highlighting its significance in optimizing drug dosages, minimizing adverse effects, and improving therapeutic efficacy. The metabolism of psychiatric medications (i.e., mood stabilizers, antipsychotics, antidepressants) often exhibits significant inter-patient variability. TDM can help address this variability by enhancing treatment personalization, facilitating early suboptimal- or toxic-level detection, and allowing for timely interventions to prevent treatment failure or adverse effects. Furthermore, this review briefly discusses technological advancements and analytical methods supporting the implementation of TDM in psychiatric settings. These innovations enable quick and cost-effective drug concentration measurements, fostering the widespread adoption of TDM as a routine practice in psychiatric care. In conclusion, the integration of TDM in psychiatry can improve treatment outcomes by individualizing medication regimens within the so-called precision medicine.

Lithium is an effective psychoactive drug. It has a narrow therapeutic margin, with subtherapeutic levels or intoxication commonly occurring. Therapeutic drug monitoring (TDM) of lithium has several barriers. This scoping review aims to describe and analyze existing and emerging technologies for lithium TDM and to describe the lithium quantification parameters (precision, accuracy, detection limit) attributed to each technology.

PubMed, Scopus, Web of Science, and Google Scholar were searched. Studies that described lithium quantification and complied with PRISMA-ScR guidelines were included. Articles selection was conducted by 2 researchers. Good precision was defined if its relative standard deviation <3%; acceptable, from 3% to 5%; and low, >5%. Accuracy was considered good if the error <5%; acceptable, 5%1 to 0%; and low if it was >10%.

Of the 2008 articles found, 22 met the inclusion criteria. Of these, 14 studies concerned laboratory devices, in which precision was found to be low in one third of cases, and half had good precision. Accuracy of one third was good, another third was low, and the remaining third did not report accuracy. The other 8 studies concerned portable devices, in which precision was low in more than 60% of the cases and good in 25% of the studies. Accuracy was low in 50% of the cases, and good in just over a third. Limits of detection included the therapeutic range of lithium in all studies.

Among emerging technologies for lithium TDM, precision and accuracy remain a challenge, particularly for portable devices.

In this work, we introduce ratiometric diffuse in vivo flow cytometry (R-DiFC) for quantitative measurement of circulating fluorescent red blood cell (fRBC) sensors for systemic blood sodium levels. Unlike in our previous work in measuring circulating fRBC sensors, R-DiFC allows simultaneous measurement of two fluorophores encapsulated in the sensor, the ratio of which enables self-calibration of the fluorescence signal with different fRBC depths in biological tissue. We show that the R-DiFC signal varies significantly less than either fluorescence signal alone. This work holds promise for personalized monitoring of systemic sodium for bipolar patients in the future.

Lithium remains the "gold standard" for both acute and maintenance treatment of bipolar disorder (BD), a serious life-long condition characterised by recurrent episodes of depressed and manic mood states. However, lithium has a very narrow therapeutic range (0.4-1.2 mmol L^-1) and despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. While it is crucial to carefully monitor lithium plasma levels, the current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Therefore, development of low-cost and facile lithium detection techniques that can be translated into point-of-care devices for personal monitoring will be a major advance in the management of BD. In the current study, we present colorimetric determination of lithium therapeutic levels utilizing test paper strips, based on its reaction with the chromogenic agent Quinizarin. Exposure of Quinizarin-dipped test papers to samples of interstitial fluid (ISF) or dH₂O spiked with therapeutic concentrations of lithium resulted in colour changes that were monitored using optical spectroscopy. The acquired spectra from the test papers show spectral variations which are related to lithium concentrations in spiked samples of dh₂O and artificial ISF with a coefficient of determination (R²) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of ¹⁰B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% energy release occurred within the cell by the nuclear reaction ¹⁰B (n, α)⁷Li, which lead to tumor cell death. The use of lithium instead of boron brings a new unique opportunity-local 100% energy release-since all products of the ⁶Li (n, α)³H reaction have high linear energy transfer characteristics. The aim of this study was to determine the concentrations of Li in the tumor, skin, blood, brain and kidney in experimental animals with B16 melanoma and to analyze the potential Li toxicity after lithium carbonate administration at single doses of 300 and 400 mg/kg. Lithium carbonate was chosen since there is a long-term experience of its use in clinical practice for the treatment of psychiatric disorders. The inductively coupled plasma atomic emission spectrometry was used to evaluate Li concentrations in tissue samples. The accumulation efficiency of Li in the tumor was the highest at a time point of 30 min (22.4 µg/g; at a dose of 400 mg/kg). Despite the high lithium accumulation in the kidneys, the pathological changes in kidney tissues were not found. Thus, lithium may actually be used for the Li-NCT development and future studies can be conducted using ⁶Li and following irradiation of tumor cells using the schemes of lithium administration tested in this work.

Therapeutic monitoring of neurotransmitters (NTs) and psychiatric medications is essential for the diagnosis and treatment of mental illness. However, in-vivo monitoring of NTs in humans as well as continuous physiological monitoring of psychiatrics have yet to be realized. In pursuit of this goal, there has been a plethora of work to develop electrochemical sensors for both in-vivo NT monitoring as well as in-vitro detection of psychiatric medications. We review these sensors here while discussing next steps needed to achieve concurrent, continuous physiological monitoring of NTs and psychiatric medications as part of a closed-loop feedback system that guides medication administration.