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Background: There has been no previous study in Thailand regarding the incidence of lithium-induced abnormal renal function. Hence, this study aimed to assess the effect of lithium maintenance therapy on chronic kidney disease, and associated factors among outpatients diagnosed with a psychiatric illness within Southern Thailand. Methods: This was a retrospective study, using an information review from the electronic medical records of Songklanagarind Hospital computer system in the last ten years; from 1 January 2013 until 31 September 2022. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and persisted for three months or more. There were 461 outpatients diagnosed with a psychiatric illness who received lithium maintenance therapy. From this, 154 outpatients were excluded: 153 received lithium therapy for less than three months and 1 presented with a baseline chronic kidney disease. All data were analyzed using Rstudio 4.3.1. The incidence of lithium-induced chronic kidney disease was analyzed by survival analysis. Results: Of the 307 outpatients diagnosed with a psychiatric illness and received lithium maintenance therapy, the most common diagnosis was bipolar disorder (59.3%). Most were female (52.8%), with the median (IQR) age of 39.0 (27.5–54.0) years. The median (IQR) age onset of lithium therapy and duration of lithium maintenance therapy were 28.0 (21.0–41.5) years, and 2.97 (0.9–9.2) years, respectively. This study identified six outpatients (1.9%) that developed chronic kidney disease stage 3 or more and one of them (0.3%) presented with chronic kidney disease stage 5 or end-stage. The incidence of lithium-induced chronic kidney disease was 0.0023 cases per exposed patient-year. When comparing outpatients who had received lithium maintenance therapy and developed chronic kidney disease with those who did not develop chronic kidney disease, this study identified that most of the group with chronic kidney disease had a lithium maintenance therapy for more than ten years, had an older age onset of lithium therapy, reported history of psychiatric hospitalization and lithium intoxication, and presented with physical illness. The associated factors between the effect of lithium maintenance therapy and chronic kidney disease could not be identified due to a limited number of outpatients having developed chronic kidney disease. Conclusions: Lithium-induced chronic kidney disease was identified as a minor incidence, and it was likely safe for maintenance therapy with careful and regular monitoring. However, older patients or those receiving lithium for a longer time and present with comorbid physical illnesses should be prescribed with caution. IRB / IEC certification: 65-389-3-4. [ABSTRACT FROM AUTHOR]

Background: Neutropenia is a noteworthy side effect of clozapine, which might warrant this drugs' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine. Methods: We retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups. Results: Of the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p =.007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p <.001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis. Conclusion: Concurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis. [ABSTRACT FROM AUTHOR]

Background: Given the large genetic heterogeneity in amyotrophic lateral sclerosis (ALS), it seems likely that genetic subgroups may benefit differently from treatment. An exploratory meta-analysis identified that patients homozygous for the C-allele at SNP rs12608932, a single nucleotide polymorphism in the gene UNC13A, had a statistically significant survival benefit when treated with lithium carbonate. We aim to confirm the efficacy of lithium carbonate on the time to death or respiratory insufficiency in patients with ALS homozygous for the C-allele at SNP rs12608932 in UNC13A.Methods: A randomized, group-sequential, event-driven, double-blind, placebo-controlled trial will be conducted in 15 sites across Europe and Australia. Patients will be genotyped for UNC13A; those homozygous for the C-allele at SNP rs12608932 will be eligible. Patients must have a diagnosis of ALS according to the revised El Escorial criteria, and a TRICALS risk-profile score between -6.0 and -2.0. An expected number of 1200 patients will be screened in order to enroll a target sample size of 171 patients. Patients will be randomly allocated in a 2:1 ratio to lithium carbonate or matching placebo, and treated for a maximum duration of 24 months. The primary endpoint is the time to death or respiratory insufficiency, whichever occurs first. Key secondary endpoints include functional decline, respiratory function, quality of life, tolerability, and safety. An interim analysis for futility and efficacy will be conducted after the occurrence of 41 events.Discussion: Lithium carbonate has been proven to be safe and well-tolerated in patients with ALS. Given the favorable safety profile, the potential benefits are considered to outweigh the burden and risks associated with study participation. This study may provide conclusive evidence about the life-prolonging potential of lithium carbonate in a genetic ALS subgroup.Trial Registration: EudraCT number 2020-000579-19 . Registered on 29 March 2021. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) combined with mood stabilizers is an effective method of treatment for manic episodes; however, there are controversial views on its side effects. Case presentation: A 53-year-old man was diagnosed with bipolar disorder during a manic episode, and had previous conditions such as hypertension, and diabetes. He developed reversible delirium and anomic aphasia during combined treatment with lithium and ECT (Li-ECT). No other neurological symptoms or signs happened during the one-month follow-up period. Conclusions: The anomic aphasia appeared after ECT was reversible. Li-ECT should be administered with caution to middle- and older-aged patients with comorbidities, and serum Li levels should be closely monitored during the treatment period. [ABSTRACT FROM AUTHOR]

Background: Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by germline mutations in the Adenomatous Polyposis Coli (APC) gene, resulting in the development of numerous colorectal adenomas. As these patients have a high risk of developing colorectal cancer (CRC), guidelines suggest prophylactic colectomy during early adulthood, however, adenoma development is still observed in the remaining intestinal tract. Therefore, FAP patients would benefit from chemoprevention strategies reducing the development of adenomas. Recent work in mice reveals a chemopreventive effect of lithium on the development of adenomas by inhibiting the expansion of Apc mutated intestinal stem cells (ISCs) within the crypts of normal intestinal mucosa. Here, we aim to investigate the effect of lithium on the spread of APC mutant cells within the human intestinal epithelium.Methods: This prospective phase II single arm trial has a duration of 18 months. FAP patients (18-35 years) with a genetically confirmed APC mutation who did not undergo colectomy will be treated with lithium carbonate orally achieving a serum level of 0.2-0.4 mmol/l between month 6 and 12. Colonoscopy with biopsies of normal intestinal mucosa will be performed at baseline and every six months. The primary endpoint is the effect of lithium on the spread of APC mutant cells within intestinal crypts over time by using APC specific marker NOTUM in situ hybridization. Secondary endpoints include change in adenoma burden, patient reported side effects and safety-outcomes. Total sample size is 12 patients and recruitment will take place in the Amsterdam UMC, location AMC in the Netherlands.Discussion: The outcome of this study will function as a proof-of-concept for the development of novel chemoprevention approaches that interfere with the competition between normal and mutant ISCs.Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT05402891 (June 1, 2022) and the EU Clinical Trials Register: EuraCT 2022-000240-30 (January 1, 2022). [ABSTRACT FROM AUTHOR]

Background: Little is known about the extent of drug entry into developing brain, when administered to pregnant and lactating women. Lithium is commonly prescribed for bipolar disorder. Here we studied transfer of lithium given to dams, into blood, brain and cerebrospinal fluid (CSF) in embryonic and postnatal animals as well as adults. Methods: Lithium chloride in a clinically relevant dose (3.2 mg/kg body weight) was injected intraperitoneally into pregnant (E15–18) and lactating dams (birth-P16/17) or directly into postnatal pups (P0–P16/17). Acute treatment involved a single injection; long-term treatment involved twice daily injections for the duration of the experiment. Following terminal anaesthesia blood plasma, CSF and brains were collected. Lithium levels and brain distribution were measured using Laser Ablation Inductively Coupled Plasma-Mass Spectrometry and total lithium levels were confirmed by Inductively Coupled Plasma-Mass Spectrometry. Results: Lithium was detected in blood, CSF and brain of all fetal and postnatal pups following lithium treatment of dams. Its concentration in pups' blood was consistently below that in maternal blood (30–35%) indicating significant protection by the placenta and breast tissue. However, much of the lithium that reached the fetus entered its brain. Levels of lithium in plasma fluctuated in different treatment groups but its concentration in CSF was stable at all ages, in agreement with known stable levels of endogenous ions in CSF. There was no significant increase of lithium transfer into CSF following application of Na+/K+ ATPase inhibitor (digoxin) in vivo, indicating that lithium transfer across choroid plexus epithelium is not likely to be via the Na+/K+ ATPase mechanism, at least early in development. Comparison with passive permeability markers suggested that in acute experiments lithium permeability was less than expected for diffusion but similar in long-term experiments at P2. Conclusions: Information obtained on the distribution of lithium in developing brain provides a basis for studying possible deleterious effects on brain development and behaviour in offspring of mothers undergoing lithium therapy. [ABSTRACT FROM AUTHOR]

Background: Lithium is prescribed during pregnancy, but there is limited information about pregnancy and neonatal outcomes following in utero exposure. Thus, this study aimed to investigate the associations between lithium use and adverse pregnancy and neonatal outcomes. Methods: This population-based cohort study examined associations between maternal lithium use and major adverse pregnancy and neonatal outcomes via inverse probability weighted propensity score regression models. Results: Of 854,017 women included in this study, 434 (0.05%) used lithium during pregnancy. Among pre-specified primary outcomes, lithium use during pregnancy was associated with an increased risk of spontaneous preterm birth (8.7% vs 3.0%; adjusted relative risk [aRR] 2.64 95% CI 1.82, 3.82) and birth of a large for gestational age infant (9.0% vs 3.5%; aRR 2.64 95% CI 1.91, 3.66), but not preeclampsia nor birth of a small for gestational age infant. Among secondary outcomes, lithium use was associated with an increased risk of cardiac malformations (2.1% vs 0.8%; aRR 3.17 95% CI 1.64, 6.13). In an analysis restricted to pregnant women with a diagnosed psychiatric illness (n=9552), associations remained between lithium and spontaneous preterm birth, birth of a large for gestational age infant, and cardiovascular malformations; and a positive association with neonatal hypoglycaemia was also found. These associations were also apparent in a further analysis comparing women who continued lithium treatment during pregnancy to those who discontinued prior to pregnancy. Conclusions: Lithium use during pregnancy is associated with an increased risk of spontaneous preterm birth and other adverse neonatal outcomes. These potential risks must be balanced against the important benefit of treatment and should be used to guide shared decision-making. [ABSTRACT FROM AUTHOR]

Background: Lithium is prescribed during pregnancy, but there is limited information about pregnancy and neonatal outcomes following in utero exposure. Thus, this study aimed to investigate the associations between lithium use and adverse pregnancy and neonatal outcomes.Methods: This population-based cohort study examined associations between maternal lithium use and major adverse pregnancy and neonatal outcomes via inverse probability weighted propensity score regression models.Results: Of 854,017 women included in this study, 434 (0.05%) used lithium during pregnancy. Among pre-specified primary outcomes, lithium use during pregnancy was associated with an increased risk of spontaneous preterm birth (8.7% vs 3.0%; adjusted relative risk [aRR] 2.64 95% CI 1.82, 3.82) and birth of a large for gestational age infant (9.0% vs 3.5%; aRR 2.64 95% CI 1.91, 3.66), but not preeclampsia nor birth of a small for gestational age infant. Among secondary outcomes, lithium use was associated with an increased risk of cardiac malformations (2.1% vs 0.8%; aRR 3.17 95% CI 1.64, 6.13). In an analysis restricted to pregnant women with a diagnosed psychiatric illness (n=9552), associations remained between lithium and spontaneous preterm birth, birth of a large for gestational age infant, and cardiovascular malformations; and a positive association with neonatal hypoglycaemia was also found. These associations were also apparent in a further analysis comparing women who continued lithium treatment during pregnancy to those who discontinued prior to pregnancy.Conclusions: Lithium use during pregnancy is associated with an increased risk of spontaneous preterm birth and other adverse neonatal outcomes. These potential risks must be balanced against the important benefit of treatment and should be used to guide shared decision-making. [ABSTRACT FROM AUTHOR]

Background: The main purpose is to investigate the effect of LiCO3 as an add-on therapy with radioactive iodine in increasing the cure and decreasing the T4 level compared to radioactive iodine alone. The primary outcome is the cure rate as defined by the number of hyperthyroid patients who became euthyroid or hypothyroid. The secondary outcome is the T4 level. Methods: Four databases were searched (PubMed, Scopus, Web of Science, and Cochrane central library). The inclusion criteria were randomized and non-randomized clinical trials of hyperthyroidism patients receiving LiCO3 with radioiodine compared with hyperthyroidism patients receiving radioactive iodine alone. Included studies were appraised with the risk of bias version 2 tool, according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Results: Nine studies were eligible for inclusion in the study, six randomized control trials and three non-randomized control trials. There were 477 patients in the intervention group and 451 patients in the control group. The cure rate was not significantly different between the two groups, while it was significantly increased with 5000 to 6500 mg optimized cumulative dose of LiCO3 compared with the control group, P = 0.0001. The T4 level showed no significant difference between the two groups, P = 0.13. Conclusions: LiCO3 adjunct to radioactive iodine did not show significant differences compared with radioactive iodine alone in terms of cure rate or decreasing T4 level. However, the dose of 5000 to 6000 mg of LiCO3 may increase the cure rate. [ABSTRACT FROM AUTHOR]

Introduction: Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling. Materials and methods: Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. Results: Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. Conclusion: The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model. [ABSTRACT FROM AUTHOR]

Background: The weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy.Methods: The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent.Discussion: The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy.Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000033633. Registered on 3 July 2018. [ABSTRACT FROM AUTHOR]

Background: Despite lithium's being the most effective drug for bipolar disorder and in clinical use for decades, we still know very little about its early effects relevant to its mode of action.Methods/design: The Oxford Lithium Trial is a double-blind, randomised, placebo-controlled study of 6-week lithium treatment in participants with bipolar disorder and mood instability. Its aim is to identify early clinical, neurocognitive and biological effects. Participants (n = 40) will undergo an intensive battery of multi-modal investigations, including remote monitoring of mood, activity and physiology, as well as cognitive testing, fMRI and magnetoencephalography, together with biochemical and gene expression measurements to assess renal, inflammatory and circadian effects.Discussion: The findings derived from this trial may be of value in predicting subsequent therapeutic response or side effects, not only relevant to the use of lithium but also providing a potential signature to help in more rapid evaluation of novel mood stabilisers. In this respect, OxLith is a step towards the development of a valid experimental medicine model for bipolar disorder.Trial Registration: ISRCTN91624955 . Registered on 22 January 2015. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. Case presentation: We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. Conclusion: The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. Case presentation: We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. Conclusion: The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia. [ABSTRACT FROM AUTHOR]

Background: The literature describing the long-term use of lithium carbonate to reinstate reduced levels of white blood cell counts in patients treated with clozapine is scarce. We describe a case of successful recommencement of clozapine on a patient who developed risk level of neutropenia which was corrected by lithium carbonate. He was followed up for a period of one year. Case presentation: We report a 40-year-old Sri Lankan male who developed neutropenia and low white blood cell counts following commencement of clozapine. We were successful in restarting clozapine after the addition of lithium carbonate to increase the cell counts. Clozapine was increased to 700 mg a day with 500 mg of lithium carbonate. The patient remains stable after one year with no further episodes of neutropenia. Conclusion: Lithium carbonate can successfully be used to treat clozapine-induced neutropenia. [ABSTRACT FROM AUTHOR]

Background: Lithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur.Case Presentation: A 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication.Conclusions: We present a rare case of lithium carbonate-induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life. [ABSTRACT FROM AUTHOR]

Abstract: Breastfeeding women often need to take medicines, and therefore health professionals need to consider the effects of medication on lactation and the breastfed infant, and any associated risks. This commentary discusses the tragic case of a young woman with a history of mental illness who committed suicide in the postpartum period. She was determined to be a 'good mother' and breastfeed, and to avoid any potential adverse effects of medication on her breastfed infant. The final outcome was fatal for both mother and child. We argue that if women require medication during lactation, all risks need to be considered - the risk of not treating the maternal medical condition may greatly outweigh the potential risk to the breastfed infant. [ABSTRACT FROM AUTHOR]

Background: Lithium, an established psychiatric medication, has recently been shown to enhance new bone formation in preclinical fracture models. Current research is focused on evaluating the efficacy of low-dose, short-term lithium treatment to improve long bone fracture healing through a Phase II randomized clinical trial (LiFT NCT02999022). In working towards future applications of lithium for fracture management, this study aimed to understand the current perceptions of lithium as a psychiatric drug and the potential barriers to its orthopaedic adoption.Methods: Three questionnaires, evaluating knowledge about lithium and willingness to embrace its use in fracture healing were disseminated among the general population, fracture patients eligible for the LiFT (Lithium for Fracture Treatment) trial and orthopaedic surgeons across Canada.Results: Of the 768 public respondents, 84% were willing to take a medication that would aid fracture healing but only 62.6% if the medication was lithium. Willingness dropped to 44.6% among the 168 respondents who knew about the psychiatric use of lithium. Lack of sufficient knowledge (n = 50) and concerns about side effects including effects on the brain (n = 74) were the main reasons cited by those who were unwilling to use lithium. Of the 29 fracture patients, only 20 patients had previously heard of lithium. Of these, 40% were willing to take lithium for fracture healing with an additional 10% if the dose was low or if the intake duration was short. Only 50% knew that lithium has side effects. Of the 43 orthopaedic surgeons, 38 surgeons knew about clinical use of lithium. Of these, 68% knew that lithium has side effects and 29% knew that it interacts with other drugs. While most agreed that new strategies are needed to improve fracture management, only 68% were willing to prescribe lithium for fractures with an additional 16% if there is scientific evidence and/or a standard dosing protocol.Conclusions: This study identified a lack of knowledge about uses and side effects of lithium among all three cohorts. A robust educational framework for orthopaedic surgeons, their patients and the members of their clinical care teams will be essential to widespread repurposing of lithium for fracture care. [ABSTRACT FROM AUTHOR]