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The experiences of patients who try drugs that aren't approved for their disease have the potential to be mined for insights into drug efficacy. Wicks et al . rapidly monitored the efficacy of lithium treatment for 149 patients with amyotrophic lateral sclerosis using an online data collection tool and a patient-matching algorithm. Patients with serious diseases may experiment with drugs that have not received regulatory approval. Online patient communities structured around quantitative outcome data have the potential to provide an observational environment to monitor such drug usage and its consequences. Here we describe an analysis of data reported on the website PatientsLikeMe by patients with amyotrophic lateral sclerosis (ALS) who experimented with lithium carbonate treatment. To reduce potential bias owing to lack of randomization, we developed an algorithm to match 149 treated patients to multiple controls (447 total) based on the progression of their disease course. At 12 months after treatment, we found no effect of lithium on disease progression. Although observational studies using unblinded data are not a substitute for double-blind randomized control trials, this study reached the same conclusion as subsequent randomized trials, suggesting that data reported by patients over the internet may be useful for accelerating clinical discovery and evaluating the effectiveness of drugs already in use.

Background Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients. Methods Lithium concentrations, Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I) scores over 24 weeks were available from 61 paediatric patients with bipolar I disorder. The population pharmacokinetics/pharmacodynamics were co-modelled. Concentrations and clinical effects following several dosage regimens were predicted by Monte Carlo simulations. Results The pharmacokinetics were well characterised by a two compartment model with linear elimination. Including the effect of total body weight (TBW) or lean body weight (LBW) on clearance and volume of distribution decreased the unexplained inter-individual variability by up to 12 %. The population mean (inter-individual variability) clearance was 1.64 L/h/53 kg LBW 0.75 (19 %) and central volume of distribution 23.6 L/53 kg LBW (6.8 %). The average lithium concentration over a dosing interval required for a 50 % reduction in YMRS was 0.711 mEq/L (59 %). A maintenance dose of 25 mg/kg TBW/day lithium carbonate in two daily doses was predicted to achieve a ≥50 % reduction in YMRS in 74 % of patients, while ~8 % of patients would be expected to have trough concentrations above the nominal safety threshold of 1.4 mEq/L. Therefore, therapeutic drug monitoring will still be required even with these dosing strategies. Conclusions When accounting for body size, the pharmacokinetic parameters in paediatric patients were within the range of estimates from adults. Pharmacokinetic/pharmacodynamic modelling supported development of practical scientifically-based dosage regimens for paediatric patients.

Lithium Carbonate is an effective treatment for affective disorders, but has a range of side effects. This case report highlights a rare side effect of Raynaud’s phenomenon following initiation of Lithium therapy in a patient with recurrent depressive disorder. He was commenced on Lithium therapy to treat severe treatment resistant depression with psychotic symptoms when alternative treatments trialled were ineffective. He had no other risk factors or known aetiological causes for development of Raynaud’s phenomenon. Symptoms resolved on discontinuation of Lithium and re-emerged on recommencement. Previous case series have shown Lithium effectively treating vasospastic disorders such as cluster headache and Raynaud’s phenomenon. However, a paradoxical reaction to those previously described was induced in this case.

Cancer involves uncontrolled cell growth, leading to tumor formation, and remains a major cause of mortality worldwide. Colorectal cancer (CRC) arises from abnormal proliferation of colon glandular epithelial cells. We assessed the cytotoxic and molecular effects of lithium carbonate (Li2CO3) and lithium chloride (LiCl) in two CRC cell lines (HCT-116 and SW-620) and a non-tumorigenic line (CRL-1790). Viability assays revealed dose-dependent cytotoxicity, with HCT-116 being the most sensitive cell line (IC50: 8.14 mM for Li2CO3). Notably, long-term lithium exposure reduced proliferation, lowering colony-forming efficiency (CFE) and a phenotypic shift from holoclones to meroclones and paraclones, indicating diminished self-renewal capacity. Minimal membrane damage was observed (LDH assay), suggesting non-lytic mechanisms consistent with apoptosis. TUNEL and Annexin-V/IP assays confirmed apoptosis in >40% of cells, without caspase-3 cleavage, suggesting a caspase-independent pathway. PARP-1 cleavage occurred only in SW-620 cells. Western blotting exposed cell-specific modulation of GSK-3β: increased inactive form (p-Ser9) in CRC cells and decreased in CRL-1790 cells, implying differential disruption of Wnt/β-catenin signaling. c-Myc levels remained unchanged, suggesting possible post-translational regulatory effects. Overall, these findings indicate that lithium salts selectively reduce CRC cell viability, impair stem-like characteristics, and induced caspase-independent apoptosis. Therefore, we expand the proof of concept of the potential of lithium-based compounds as low-toxicity adjuvant agents in colorectal cancer therapy.

Background Hyperthyroidism poses challenges, and common treatments like Radioactive Iodine (RAI) have limitations, prompting exploration of adjunctive approaches. This meta-analysis evaluates the combined impact of RAI and Lithium carbonate (LiCO3) on cure rates and thyroid hormone levels. Methods We systematically searched Cochrane Library, PubMed, Scopus, and Web of Science for studies comparing LiCO3 combined with RAI to RAI alone. Pooled results analyzed cure rates and Free T3/T4 changes. A subgroup analysis was conducted based on LiCO3 dosage and treatment duration, while meta-regression was performed to assess covariates such as the patient’s age, RAI dose, and lithium dose. The risk of bias was evaluated using ROB2, ROBINS-1, and NOS, while the statistical analyses were conducted using Revman software 5.4.1. Results Analysis of 14 studies involving 2047 patients revealed a significantly increased cure rate with RAI and LiCO3 compared to RAI alone (RR 1.12, 95% CI [1.03,1.23], p  = 0.01). Subgroup analysis revealed higher cure rates with short-duration intensified doses of LiCO3, while short-duration diluted doses reduced cure rates. No significant differences were noted in euthyroid and hypothyroid states. Changes in free T3 showed no significant difference between the arms at 7 days and the most common time point. A significant decrease in free T4 favored RAI with LiCO3 at 7 days (MD -4.90, 95% CI [-7.91, -1.89], p  = 0.001), and the most common time point (MD -3.83, 95% CI [-7.45, -0.20], p  = 0.04). Meta-regression analysis indicated better cure rates in older patients ( p  < 0.001) and lower total lithium doses ( p  < 0.001). Conclusion Treatment with RAI combined with LiCO3 significantly enhanced cure rates, particularly when using short-duration intensified doses of LiCO3. Additionally, LiCO3 effectively reduced T4 levels without altering T3 levels. Future research is needed to validate our findings. Clinical trial number Not applicable.

In 2019 in the US, 7,085 toxic lithium exposures were documented. This refers to substantial exposures that may have resulted in a clinical outcome of at least moderate severity. Of these, 22% resulted in serious clinical consequences, including 4 deaths. Lithium has a narrow therapeutic index and a wide range of toxicities. It is an effective and widely prescribed therapy for bipolar disorder and is also used off label for other psychiatric disorders. It is available in both immediate-release and sustained-re lease preparations. The recommended therapeutic range varies with patient age, owing to age-related changes in renal function and increased prevalence of polypharmacy and drug interactions. Lithium is an inorganic monovalent cation with a small molecular weight of 7 Da. It is rapidly absorbed, not protein bound, has a low volume of distribution between 0.6 and 0.9 L/kg, and is freely excreted unchanged via the kidneys. Here, Kobylianskii et al examine the case of 54-year-old woman with chronic lithium toxicity.

Lithium, a natural element, has been employed as a mental stabilizer in psychiatric treatments; however, some reports indicate it has an anticancer effect, prompting the consideration of repurposing lithium for cancer treatment. The potential anticancer use of lithium may depend on its form (salt type) and the type of cancer cells targeted. Little is known about the effects of Li2CO3 or LiCl on cancer cells, so we focused on exploring their effects on proliferation, apoptosis, migration, and cell cycle as part of the hallmarks of cancer. Firstly, we established the IC50 values on HeLa, SiHa, and HaCaT cells with LiCl and Li2CO3 and determined by crystal violet that cell proliferation was time-dependent in the three cell lines (IC50 values for LiCl were 23.43 mM for SiHa, 23.14 mM for HeLa, and 15.10 mM for HaCaT cells, while the IC50 values for Li2CO3 were 20.57 mM for SiHa, 11.52 mM for HeLa, and 10.52 mM for HaCaT cells.) Our findings indicate that Li2CO3 and LiCl induce DNA fragmentation and caspase-independent apoptosis, as shown by TUNEL, Western Blot, and Annexin V/IP assay by flow cytometry. Also, cell cycle analysis showed that LiCl and Li2CO3 arrested the cervical cancer cells at the G1 phase. Moreover, lithium salts displayed an anti-migratory effect on the three cell lines observed by the wound-healing assay. All these findings imply the viable anticancer effect of lithium salts by targeting several of the hallmarks of cancer.

The magnesium impurities in lithium carbonate cannot be detected quickly in an aqueous environment. To solve this bottleneck problem, this study proposes a new method for the rapid detection of trace Mg2+ in lithium carbonate using a water-soluble fluorescent probe. A water-soluble fluorescent probe A was obtained by introducing hydroxyl groups on a fluorescent oxazole ring. After modification, the hydrogen bonding between the probe and water molecules increased by more than 62 times. Consequently, the energy loss of outward transfer of the fluorescent probe increased, resulting in weak fluorescence in saline systems. Mg2+ was captured by N on the oxazole ring and O on the phenolic hydroxyl group through a 1:1 coordination ratio within the probe structure. The hydrogen bonding attraction between the complex and water molecules increased 16 times. Additionally, the orbital energy gap was reduced from 2.817 to 0.383 eV. Meanwhile, the Mg2+ impeded the phototropic electron transfer effect process, resulting in enhanced fluorescence and completing this process within 3 to 10 s, with a detection limit of 6.06 μmol/L. This method can promote the real-time and rapid quality control of Mg2+ impurities in the refining and purification of lithium carbonate, as well as effectively reduce production costs.

Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and serious side effect of many cytotoxic drugs, including paclitaxel. Despite the identification of treatment options in animal models, clinical trials for the treatment or prevention of CIPN have been negative. Major challenges for successful clinical translation of preclinical data include a lack of reproducibility and randomization, small sample sizes and insufficient statistical tests. We therefore conducted a confirmatory, preclinical multicenter randomized controlled replication trial to test the safety and efficacy of three drugs for preventing paclitaxel-induced polyneuropathy: (1) nilotinib, (2) lithium carbonate and (3) interleukin-6-neutralizing antibodies. We preregistered the data analysis plan as well as the two-step study protocol: the optimal doses of the three compounds were assessed first and then tested in a mouse breast cancer xenograft model to compare safety and efficacy. Results Unfortunately, toxicity of intraperitoneally administered nilotinib in combination with paclitaxel was observed, and higher-than-expected tumor growth resulted in a lack of power when the trial was analyzed. Thus, although lithium carbonate and IL-6-neutralizing antibodies tended toward neuroprotection, the differences between these groups were not statistically significant. However, the PINPRICS study ultimately still provides important lessons with regard to the planning and conduction of multicenter preclinical trials.

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li+) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation. The results showed that compared with OGNa and LC, OGLi significantly reduced the clinical symptoms and histopathological changes associated with UC in the acute model. It was worth noting that OGLi significantly changed the gut microbiota characteristics of the DSS-treated mice and corrected the typical dysbacteriosis of DSS-induced UC. This intervention resulted in increasing the abundance of norank_f_Muribaculaceae and Ileibacterium spp. while reducing the levels of Escherichia-Shigella spp. and Romboutsia spp. The OGLi could significantly increase the diversity of intestinal microorganisms in the short term. All of these discoveries demonstrate that lithium collaboratively enhances the anti-UC efficacy of OG, which will help to create OG-based drugs for the treatment of UC.