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CNS Neuroscience & Therapeutics Mar 2012Still after more than 50 years, lithium is a major treatment of bipolar disorder, even though it has not been promoted by the pharmaceutical industry over the last... (Review)
Review
Still after more than 50 years, lithium is a major treatment of bipolar disorder, even though it has not been promoted by the pharmaceutical industry over the last decades. In recent years the evidence base on lithium for bipolar disorder has substantially increased due to results from a number of trials. Therefore, a review of this evidence is timely. The efficacy of lithium as an acute treatment and as a maintenance treatment of bipolar disorder was evaluated through a review of the evidence, focusing on modern, randomized, parallel-group designed trials. Additionally, the evidence was sought translated into the proper use of lithium in clinical practice. Lithium's antimanic efficacy has been convincingly demonstrated. However, as blood monitoring due to the risk of toxicity is required and due to an insufficient response in highly agitated patients, lithium monotherapy has a limited place in the acute treatment of severe manic states. For acute bipolar depression, results are conflicting. Recent maintenance trials have added substantially to the documentation of lithium's long-term stabilizing properties in bipolar disorder, and these properties have been demonstrated independently of any acute response to lithium. Finally, it is now beyond doubt that not only does lithium prevent mania, but also depression in bipolar disorder. Lithium is still to be considered a major if not the most important mood- stabilizer, at least for maintaining long-term stability in patients with bipolar disorder. The potential risks of lithium should be weighed up against its benefits and the fact that serious adverse effects are usually avoidable.
Topics: Antimanic Agents; Bipolar Disorder; Disease Management; Drug Therapy, Combination; Humans; Lithium; Randomized Controlled Trials as Topic
PubMed: 22070642
DOI: 10.1111/j.1755-5949.2011.00260.x -
Postgraduate Medical Journal Oct 1979The peripheral and central neurotoxic effects of lithium carbonate are illustrated by 4 case histories. Lithium neurotoxicity is likely to be more common than the...
The peripheral and central neurotoxic effects of lithium carbonate are illustrated by 4 case histories. Lithium neurotoxicity is likely to be more common than the literature suggests. Neurological sequelae may be irreversible and may be associated with therapeutic serum levels. Prevention may be facilitated by more stringent case selection, EEG and clinical monitoring and the development of improved methods of drug level assessment.
Topics: Adult; Central Nervous System Diseases; Female; Humans; Lithium; Male; Middle Aged
PubMed: 537955
DOI: 10.1136/pgmj.55.648.701 -
British Journal of Pharmacology Jul 2018Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in G -protein coupled receptor signalling. Recently, the...
BACKGROUND AND PURPOSE
Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in G -protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5-HT receptor, a G -protein coupled receptor involved in lithium's actions.
EXPERIMENTAL APPROACH
5-HT receptor function was assessed in mice by measuring the behavioural (head-twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c-fos, Egr2) responses to 5-HT receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5-HT receptor function. Because lithium and 5-HT receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments.
KEY RESULTS
Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen enhanced the increase in extracellular 5-HT induced by citalopram, and also increased regional brain 5-HT synthesis.
CONCLUSIONS AND IMPLICATIONS
Our data demonstrated lithium-mimetic effects of ebselen in different experimental models of 5-HT receptor function, probably mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent.
Topics: Animals; Antioxidants; Azoles; Dose-Response Relationship, Drug; Isoindoles; Lithium; Male; Mice; Mice, Inbred C57BL; Organoselenium Compounds; Receptor, Serotonin, 5-HT2A
PubMed: 29488218
DOI: 10.1111/bph.14179 -
Molecules (Basel, Switzerland) Jan 2021In recent years, the applications of lithium-ion batteries have emerged promptly owing to its widespread use in portable electronics and electric vehicles. Nevertheless,... (Review)
Review
In recent years, the applications of lithium-ion batteries have emerged promptly owing to its widespread use in portable electronics and electric vehicles. Nevertheless, the safety of the battery systems has always been a global concern for the end-users. The separator is an indispensable part of lithium-ion batteries since it functions as a physical barrier for the electrode as well as an electrolyte reservoir for ionic transport. The properties of separators have direct influences on the performance of lithium-ion batteries, therefore the separators play an important role in the battery safety issue. With the rapid developments of applied materials, there have been extensive efforts to utilize these new materials as battery separators with enhanced electrical, fire, and explosion prevention performances. In this review, we aim to deliver an overview of recent advancements in numerical models on battery separators. Moreover, we summarize the physical properties of separators and benchmark selective key performance indicators. A broad picture of recent simulation studies on separators is given and a brief outlook for the future directions is also proposed.
Topics: Electric Power Supplies; Electrodes; Ions; Lithium
PubMed: 33477513
DOI: 10.3390/molecules26020478 -
Chemosphere Apr 2024This review critically examines the effectiveness of ion-imprinted membranes (IIMs) in selectively recovering lithium (Li) from challenging sources such as seawater and... (Review)
Review
This review critically examines the effectiveness of ion-imprinted membranes (IIMs) in selectively recovering lithium (Li) from challenging sources such as seawater and brine. These membranes feature customized binding sites that specifically target Li ions, enabling selective separation from other ions, thanks to cavities shaped with crown ether or calixarene for improved selectivity. The review thoroughly investigates the application of IIMs in Li extraction, covering extensive sections on 12-crown-4 ether (a fundamental crown ether for Li), its modifications, calixarenes, and other materials for creating imprinting sites. It evaluates these systems against several criteria, including the source solution's complexity, Li concentration, operational pH, selectivity, and membrane's ability for regeneration and repeated use. This evaluation places IIMs as a leading-edge technology for Li extraction, surpassing traditional methods like ion-sieves, particularly in high Mg/Li ratio brines. It also highlights the developmental challenges of IIMs, focusing on optimizing adsorption, maintaining selectivity across varied ionic solutions, and enhancing permselectivity. The review reveals that while the bulk of research is still exploratory, only a limited portion has progressed to detailed lab verification, indicating that the application of IIMs in Li recovery is still at an embryonic stage, with no instances of pilot-scale trials reported. This thorough review elucidates the potential of IIMs in Li recovery, cataloging advancements, pinpointing challenges, and suggesting directions for forthcoming research endeavors. This informative synthesis serves as a valuable resource for both the scientific community and industry professionals navigating this evolving field.
Topics: Crown Ethers; Lithium; Ions; Adsorption
PubMed: 38462186
DOI: 10.1016/j.chemosphere.2024.141674 -
International Journal of Molecular... Dec 2020Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's... (Review)
Review
Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug's inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium's neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer's disease (AD) and in patients, discussing the rationale for the drug's use in the treatment of AD.
Topics: Alzheimer Disease; Animals; Apoptosis; Autophagy; Bipolar Disorder; Drug Repositioning; Glycogen Synthase Kinase 3; Homeostasis; Humans; Lithium; Neurodegenerative Diseases; Neuroprotective Agents; Oxidative Stress; Phosphoric Monoester Hydrolases
PubMed: 33375448
DOI: 10.3390/ijms22010189 -
Acta Psychiatrica Scandinavica Nov 2013Lithium (Li) is often an effective treatment for mood disorders, especially bipolar disorder (BPD), and can mitigate the effects of stress on the brain by modulating... (Review)
Review
OBJECTIVE
Lithium (Li) is often an effective treatment for mood disorders, especially bipolar disorder (BPD), and can mitigate the effects of stress on the brain by modulating several pathways to facilitate neural plasticity. This review seeks to summarize what is known about the molecular mechanisms underlying Li's actions in the brain in response to stress, particularly how Li is able to facilitate plasticity through regulation of the glutamate system and cytoskeletal components.
METHOD
The authors conducted an extensive search of the published literature using several search terms, including Li, plasticity, and stress. Relevant articles were retrieved, and their bibliographies consulted to expand the number of articles reviewed. The most relevant articles from both the clinical and preclinical literature were examined in detail.
RESULTS
Chronic stress results in morphological and functional remodeling in specific brain regions where structural differences have been associated with mood disorders, such as BPD. Li has been shown to block stress-induced changes and facilitate neural plasticity. The onset of mood disorders may reflect an inability of the brain to properly respond after stress, where changes in certain regions may become 'locked in' when plasticity is lost. Li can enhance plasticity through several molecular mechanisms, which have been characterized in animal models. Further, the expanding number of clinical imaging studies has provided evidence that these mechanisms may be at work in the human brain.
CONCLUSION
This work supports the hypothesis that Li is able to improve clinical symptoms by facilitating neural plasticity and thereby helps to 'unlock' the brain from its maladaptive state in patients with mood disorders.
Topics: Antimanic Agents; Brain; Humans; Lithium; Mood Disorders; Neuronal Plasticity; Stress, Psychological
PubMed: 23617566
DOI: 10.1111/acps.12139 -
Scientific Reports Jan 2021Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its...
Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen's kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [- 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.
Topics: Adolescent; Adult; Bipolar Disorder; Female; Genomics; Humans; Lithium; Machine Learning; Male; Models, Genetic; Polymorphism, Single Nucleotide; Prognosis; Treatment Outcome; Young Adult
PubMed: 33441847
DOI: 10.1038/s41598-020-80814-z -
Trials Nov 2021Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of some chemotherapy regimens. Lithium has been suggested for CIPN in some animal studies.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of some chemotherapy regimens. Lithium has been suggested for CIPN in some animal studies. We aimed to study lithium's preventive effect on CIPN in breast cancer patients treated with taxanes and platinum-based medications.
METHOD
A double-blind placebo-controlled randomized clinical trial (RCT) was implemented on 36 breast cancer patients in two equal-size groups by block randomization. Participants in both groups consumed daily tablets, either placebo or lithium (300 mg), for 5 days in each course of chemotherapy. The tablets were prescribed 1 day before the start of chemotherapy. The electromyography (EMG) and nerve-conduction-velocity (NCV) tests were achieved before the first chemotherapy, 3 and 9 months after the treatment. The changes and signs or symptoms of CIPN, such as numbness, tingling, freezing, sensitivity to touch, muscle weakness, fibrillation, and knee and elbow reflex disorders, were recorded by examination. The trend of outcome changes was compared between two groups during the 9 months of study.
RESULTS
In both groups, neurologic signs and symptoms were exacerbated during the first 3 months and improved up to the ninth month of study. Results showed significant changes of all EMG-NCV variables during the 9 months of research in each group (P < 0.001), but the interaction of time and group effect was not significant in none of those indices. All symptoms changed significantly over the study time (P < 0.001) without significant statistical difference between the two groups (P=0.352). No side effect was found during the study.
CONCLUSION
The study showed that 300 mg lithium prescription once daily for 5 days might not effectively prevent CIPN in breast cancer patients. Evaluation of lithium effect on CIPN on different cancers in future studies is suggested.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials IRCT20160813029327N10 . Registration date: May 16, 2018.
Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Lithium; Peripheral Nervous System Diseases; Taxoids
PubMed: 34819131
DOI: 10.1186/s13063-021-05800-w -
Neuropharmacology Feb 2017The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the...
The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro. We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response.
Topics: Animals; Brain; Cells, Cultured; Drug Administration Schedule; Lithium; Locomotion; Male; Mice; Mice, Inbred C57BL; Models, Animal; Neurons; Rats; Transcription Factor 7-Like 2 Protein; Zebrafish
PubMed: 27793772
DOI: 10.1016/j.neuropharm.2016.10.027