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Current Neuropharmacology 2023Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration),... (Review)
Review
Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration), there is a stigma associated with lithium treatment and the adverse effects that can occur at therapeutic doses. However, several studies have indicated that doses of lithium under the predetermined therapeutic dose used in bipolar disorder treatment may have beneficial effects not only in the brain but across the body. Currently, literature shows that low-dose lithium (≤0.5 mM) may be beneficial for cardiovascular, musculoskeletal, metabolic, and cognitive function, as well as inflammatory and antioxidant processes of the aging body. There is also some evidence of low-dose lithium exerting a similar and sometimes synergistic effect on these systems. This review summarizes these findings with a focus on low-dose lithium's potential benefits on the aging process and age-related diseases of these systems, such as cardiovascular disease, osteoporosis, sarcopenia, obesity and type 2 diabetes, Alzheimer's disease, and the chronic low-grade inflammatory state known as inflammaging. Although lithium's actions have been widely studied in the brain, the study of the potential benefits of lithium, particularly at a low dose, is still relatively novel. Therefore, this review aims to provide possible mechanistic insights for future research in this field.
Topics: Humans; Lithium; Diabetes Mellitus, Type 2; Bipolar Disorder; Brain; Dietary Supplements
PubMed: 35236261
DOI: 10.2174/1570159X20666220302151224 -
International Journal of Molecular... Jul 2018In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and... (Review)
Review
In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.
Topics: Animals; Bipolar Disorder; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Lithium; Psychopharmacology; Tranquilizing Agents
PubMed: 30041458
DOI: 10.3390/ijms19072143 -
International Journal of Molecular... Dec 2017Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines... (Review)
Review
Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium's specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3β, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium.
Topics: Bipolar Disorder; Glycogen Synthase Kinase 3 beta; Humans; Lithium; Nerve Growth Factors; Neuronal Plasticity; Neuroprotection
PubMed: 29232923
DOI: 10.3390/ijms18122679 -
Neuroscience Letters Apr 2022This mini-review aims to show a discrepancy between favorable data of lithium's therapeutic activity and the decreased use of the drug worldwide. The data point to... (Review)
Review
This mini-review aims to show a discrepancy between favorable data of lithium's therapeutic activity and the decreased use of the drug worldwide. The data point to lithium as the best mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most encouraging psychiatric use of lithium is the augmentation of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium is the most efficacious antisuicidal drug among all mood stabilizers. The drug also exerts antiviral, immunomodulatory, and neuroprotective effects which may be of major clinical value. On the other hand, the data of lithium use show that its therapeutic application in many countries has declined. A reason for this can be the introduction and heavy promotion of other mood-stabilizers, while lithium is an "orphan" drug with the minimal interest of any drug company. Probably, very important is also a perception of lithium as a "toxic drug", pointing to its side effects, mainly thyroid, renal and cognitive ones. In recent years, several proposals to turn back this anomalous association appeared, challenging a negative perception of lithium and optimizing its long-term administration. They show the data on lithium superiority over other mood stabilizers and point to the proper management of the lithium-induced side effects. This endeavor aims to allow a larger number of mood disorder patients to become beneficiaries of lithium use.
Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds
PubMed: 35346779
DOI: 10.1016/j.neulet.2022.136590 -
Current Neuropharmacology 2022Lithium is a well-known FDA-approved treatment for bipolar and mood disorders. Lithium has been an enigmatic drug with multifaceted actions involving various... (Review)
Review
Lithium is a well-known FDA-approved treatment for bipolar and mood disorders. Lithium has been an enigmatic drug with multifaceted actions involving various neurotransmitters and intricate cell signalling cascades. Recent studies highlight the neuroprotective and neurotrophic actions of lithium in amyotrophic lateral sclerosis, Alzheimer's disease, intracerebral hemorrhage, and epilepsy. Of note, lithium holds a significant interest in epilepsy, where the past reports expose its non-specific proconvulsant action, followed lately by numerous studies for anti-convulsant action. However, the exact mechanism of action of lithium for any of its effects is still largely unknown. The present review integrates findings from several reports and provides detailed possible mechanisms of how a single molecule exhibits marked pro-epileptogenic as well as anti-convulsant action. This review also provides clarity regarding the safety of lithium therapy in epileptic patients.
Topics: Epilepsy; Humans; Lithium; Lithium Compounds; Mood Disorders; Neuroprotection
PubMed: 35410603
DOI: 10.2174/1570159X20666220411081728 -
Journal of Integrative Neuroscience Mar 2022Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive... (Review)
Review
Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.
Topics: Animals; Antiviral Agents; Bipolar Disorder; Lithium; Lithium Compounds; Neuroprotective Agents
PubMed: 35364656
DOI: 10.31083/j.jin2102068 -
International Journal of Molecular... Jan 2022The mood stabilizer lithium represents a cornerstone in the long term treatment of bipolar disorder (BD), although with substantial interindividual variability in... (Review)
Review
The mood stabilizer lithium represents a cornerstone in the long term treatment of bipolar disorder (BD), although with substantial interindividual variability in clinical response. This variability appears to be modulated by genetics, which has been significantly investigated in the last two decades with some promising findings. In addition, recently, the interest in the role of epigenetics has grown significantly, since the exploration of these mechanisms might allow the elucidation of the gene-environment interactions and explanation of missing heritability. In this article, we provide an overview of the most relevant findings regarding the pharmacogenomics and pharmacoepigenomics of lithium response in BD. We describe the most replicated findings among candidate gene studies, results from genome-wide association studies (GWAS) as well as post-GWAS approaches supporting an association between high genetic load for schizophrenia, major depressive disorder or attention deficit/hyperactivity disorder and poor lithium response. Next, we describe results from studies investigating epigenetic mechanisms, such as changes in methylation or noncoding RNA levels, which play a relevant role as regulators of gene expression. Finally, we discuss challenges related to the search for the molecular determinants of lithium response and potential future research directions to pave the path towards a biomarker guided approach in lithium treatment.
Topics: Animals; Biomarkers; Body Fluids; DNA Methylation; Epigenesis, Genetic; Genome-Wide Association Study; Humans; Lithium
PubMed: 35163479
DOI: 10.3390/ijms23031555 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Clinical Cardiology Dec 2017Lithium has been used for the treatment of bipolar disorder for more than 6 decades. Reports of cardiac side effects resulting in both benign electrocardiographic (ECG)... (Review)
Review
Lithium has been used for the treatment of bipolar disorder for more than 6 decades. Reports of cardiac side effects resulting in both benign electrocardiographic (ECG) changes and near fatal arrhythmias have been reported in the literature. A systematic literature search was conducted on 2 electronic databases-PubMed and Medline-for the time period between January 1970 and March 2016 using the key word "lithium," along with "electrocardiography" or "ECG." All articles and their references were then screened by title for relevance by 2 authors and a librarian. A total of 406 articles were found on literature search, of which 56 met the screening criteria. T wave inversion was the most frequently reported ECG finding. Other findings include sinus node dysfunction, sinoatrial blocks, PR prolongation, QT prolongation/dispersion, and ventricular tachyarrhythmias. Some cases have shown lithium-treated patients experiencing serious cardiac outcomes, such as ST elevation myocardial infarction, heart blocks, and the Brugada pattern. Electrical changes from lithium were found to be dependent on both duration of treatment and the serum lithium level. Although there are no standardized ECG guidelines, frequent monitoring of patients on lithium therapy can ensure the medication's safe use.
Topics: Arrhythmias, Cardiac; Bipolar Disorder; Electrocardiography; Global Health; Humans; Incidence; Lithium; Survival Rate
PubMed: 29247520
DOI: 10.1002/clc.22822 -
International Journal of Molecular... Sep 2022Bipolar disorder (BD) is a severe, chronic, and disabling neuropsychiatric disorder characterized by recurrent mood disturbances (mania/hypomania and depression, with or... (Review)
Review
Bipolar disorder (BD) is a severe, chronic, and disabling neuropsychiatric disorder characterized by recurrent mood disturbances (mania/hypomania and depression, with or without mixed features) and a constellation of cognitive, psychomotor, autonomic, and endocrine abnormalities. The etiology of BD is multifactorial, including both biological and epigenetic factors. Recently, microRNAs (miRNAs), a class of epigenetic regulators of gene expression playing a central role in brain development and plasticity, have been related to several neuropsychiatric disorders, including BD. Moreover, an alteration in the number/distribution and differentiation potential of neural stem cells has also been described, significantly affecting brain homeostasis and neuroplasticity. This review aimed to evaluate the most reliable scientific evidence on miRNAs as biomarkers for the diagnosis of BD and assess their implications in response to mood stabilizers, such as lithium. Neural stem cell distribution, regulation, and dysfunction in the etiology of BD are also dissected.
Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium; MicroRNAs; Stem Cells
PubMed: 36142403
DOI: 10.3390/ijms231810489