ABSTRACT
Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures.
Subject(s)
Antimanic Agents , Antipsychotic Agents , Bipolar Disorder , Fractures, Bone , Humans , Bipolar Disorder/drug therapy , Bipolar Disorder/epidemiology , Female , Male , Middle Aged , Adult , Antipsychotic Agents/adverse effects , Fractures, Bone/epidemiology , Fractures, Bone/chemically induced , Antimanic Agents/adverse effects , Antimanic Agents/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Cohort Studies , Lithium Compounds/adverse effects , Lithium Compounds/therapeutic use , Aged , United Kingdom/epidemiology , Lithium/therapeutic use , Lithium/adverse effectsABSTRACT
INTRODUCTION: Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI. METHOD: The "Boolean logic" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar. RESULTS: Lithium's therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor-mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short- as well as long-term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo-cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI. CONCLUSION: Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI.
Subject(s)
Brain Injuries, Traumatic , Neuroprotective Agents , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/administration & dosage , Animals , Lithium/pharmacology , Lithium/therapeutic use , Brain/drug effects , Brain/metabolism , Lithium Compounds/pharmacologyABSTRACT
AIMS: Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders. METHODS: This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy. RESULTS: Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk. CONCLUSION: Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.
Subject(s)
Antimanic Agents , Antipsychotic Agents , Bipolar Disorder , Propensity Score , Quetiapine Fumarate , Valproic Acid , Humans , Bipolar Disorder/drug therapy , Bipolar Disorder/mortality , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Female , Male , Adult , Middle Aged , Valproic Acid/therapeutic use , Antimanic Agents/therapeutic use , Cohort Studies , Quetiapine Fumarate/therapeutic use , Quetiapine Fumarate/adverse effects , Olanzapine/therapeutic use , Hong Kong/epidemiology , Risperidone/therapeutic use , Risperidone/adverse effects , Lithium/therapeutic use , Cause of DeathABSTRACT
BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric illness affecting â¼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive. METHODS: In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies. FINDINGS: We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with changes to Na+ conductance. Whole transcriptome sequencing in BD neurons revealed altered gene expression pathways related to glutamate transmission, alterations in cell signalling and ion transport/channel activity. We found altered Akt signalling as a potential therapeutic effect of Li in LR neurons from patients with BD, and that Akt activation mimics Li effect in LR neurons. Furthermore, the increased neural network activity observed in both LR & LNR neurons from patients with BD were reversed by AMP-activated protein kinase (AMPK) activation. INTERPRETATION: These results suggest potential for new treatment strategies in BD, such as Akt activators in LR cases, and the use of AMPK activators for LNR patients with BD. FUNDING: Supported by funding from ERA PerMed, Bell Brain Canada Mental Research Program and Brain & Behavior Research Foundation.
Subject(s)
AMP-Activated Protein Kinases , Bipolar Disorder , Induced Pluripotent Stem Cells , Neurons , Proto-Oncogene Proteins c-akt , Bipolar Disorder/metabolism , Bipolar Disorder/drug therapy , Humans , Neurons/metabolism , AMP-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Lithium/pharmacology , Lithium/therapeutic use , Signal Transduction , Gene Expression Profiling , TranscriptomeABSTRACT
ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.
Subject(s)
Bipolar Disorder , Drug Monitoring , Neuromyelitis Optica , Plasmapheresis , Humans , Antimanic Agents/therapeutic use , Antimanic Agents/blood , Bipolar Disorder/therapy , Bipolar Disorder/blood , Drug Monitoring/methods , Intensive Care Units , Lithium/blood , Lithium/therapeutic use , Neuromyelitis Optica/therapy , Neuromyelitis Optica/blood , Plasmapheresis/methodsABSTRACT
BACKGROUND: The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLi+Gen). METHODS: We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg. RESULTS: The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium. LIMITATIONS: Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies. CONCLUSIONS: The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption.
Subject(s)
Bipolar Disorder , Computer Simulation , Intestinal Absorption , Serine Endopeptidases , Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Bipolar Disorder/metabolism , Humans , Intestinal Absorption/drug effects , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Mice , Animals , Membrane Proteins/genetics , Membrane Proteins/metabolism , Lithium/therapeutic use , Lithium/pharmacology , Antimanic Agents/pharmacology , Antimanic Agents/therapeutic use , Genome-Wide Association Study , Lithium Compounds/pharmacology , Lithium Compounds/therapeutic use , Lithium Compounds/pharmacokineticsABSTRACT
BACKGROUND Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI.
Subject(s)
Diabetes Insipidus, Nephrogenic , Diabetes Mellitus , Hypernatremia , Female , Humans , Middle Aged , Diabetes Insipidus, Nephrogenic/chemically induced , Diabetes Insipidus, Nephrogenic/drug therapy , Lithium/therapeutic use , Celecoxib/therapeutic use , Polyuria/chemically induced , Polyuria/drug therapy , Hypernatremia/chemically induced , Hypernatremia/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diabetes Mellitus/drug therapy , SodiumABSTRACT
Alzheimer's disease (AD) is the most common neuronal disorder that leads to the development of dementia. Until nowadays, some therapies may alleviate the symptoms, but there is no pharmacological treatment. Microdosing lithium has been used to modify the pathological characteristics of the disease, with effects in both experimental and clinical conditions. The present work aimed to analyze the effects of this treatment on spatial memory, anxiety, and molecular mechanisms related to long-term memory formation during the aging process of a mouse model of accelerated aging (SAMP-8). Female SAMP-8 showed learning and memory impairments together with disruption of memory mechanisms, neuronal loss, and increased density of senile plaques compared to their natural control strain, the senescence-accelerated mouse resistant (SAMR-1). Chronic treatment with lithium promoted memory maintenance, reduction in anxiety, and maintenance of proteins related to memory formation and neuronal density. The density of senile plaques was also reduced. An increase in the density of gamma-aminobutyric acid A (GABAA) and α7 nicotinic cholinergic receptors was also observed and related to neuroprotection and anxiety reduction. In addition, this microdose of lithium inhibited the activation of glycogen synthase kinase-3beta (GSK-3ß), the classical mechanism of lithium cell effects, which could contribute to the preservation of the memory mechanism and reduction in senile plaque formation. This work shows that lithium effects in neuroprotection along the aging process are not related to a unique cellular mechanism but produce multiple effects that slowly protect the brain along the aging process.
Subject(s)
Alzheimer Disease , Lithium , Phenylmercury Compounds , Mice , Female , Animals , Lithium/pharmacology , Lithium/therapeutic use , Plaque, Amyloid/pathology , Glycogen Synthase Kinase 3 beta , Alzheimer Disease/pathology , Aging/metabolism , Disease Models, AnimalABSTRACT
This is a case of a 35-year-old woman who presented with an 18-month history of post (long)-COVID depression and exhaustion along with recurrent fevers and treatment-resistant skin boils, all of which abated with lithium treatment at a serum level of 1.14 mmol/L, and all of which worsened when the lithium serum level was lowered to 0.8. This paper illustrates Lithium's effectiveness in the treatment of post (long)-COVID syndrome, though a higher serum concentration may be required.
Subject(s)
COVID-19 , Lithium , Female , Humans , Adult , Lithium/therapeutic use , Depression , Lithium Compounds/therapeutic useABSTRACT
The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. Overall, we observed relatively weak associations (p < 1 × 10-4) with BP phenotypes within immune-related genes. Network and functional enrichment analyses of the top findings from the association analyses of Li response variables showed an overrepresentation of pathways participating in cell adhesion and intercellular communication. These appeared to converge on the well-known Li-induced inhibition of GSK-3ß. Association analyses of age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation suggested modest contributions of genes such as RTN4, XKR4, NRXN1, NRG1/3 and GRK5 to disease characteristics. PGS analyses returned weak associations (p < 0.05) between inflammation markers and the studied BP phenotypes. Our results suggest a modest relationship between immunity and clinical features in BP. More research is needed to assess the potential therapeutic relevance.
Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Bipolar Disorder/psychology , Lithium/therapeutic use , Retrospective Studies , Immunogenetics , Glycogen Synthase Kinase 3 beta , PhenotypeABSTRACT
INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.
Subject(s)
Alzheimer Disease , Dementia , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/epidemiology , Dementia/epidemiology , Dementia/drug therapy , Lithium Compounds/therapeutic use , Prevalence , Lithium/therapeutic use , Neuroprotective Agents/therapeutic useABSTRACT
Bipolar disorder with a rapid cycling course can be difficult to treat, often involving therapy resistance. A 55-year old patient with bipolar disorder with rapid cycling course did not stabilize for years, despite various pharmacotherapeutic treatments. Only after lithium was introduced as a maintenance treatment at a level of around 1.20 mmol/l, a long-term stabilization of mood developed which also persisted. A literature review was performed which concluded that maintenance treatment with lithium at levels above 1.0 mmol/l in patients with rapid cycling bipolar disorder has not been adequately studied.
Subject(s)
Bipolar Disorder , Humans , Middle Aged , Bipolar Disorder/drug therapy , Lithium/therapeutic useABSTRACT
BACKGROUND: Immune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. METHODS: We investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. RESULTS: In comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. LIMITATIONS: The cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. CONCLUSION: The altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium.
Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/genetics , Lithium/pharmacology , Lithium/therapeutic use , CD8-Positive T-Lymphocytes/metabolism , Cross-Sectional Studies , Mitochondria/metabolism , Lithium Compounds/therapeutic use , Lithium Compounds/pharmacologyABSTRACT
Bipolar disorder is a complex mental illness. Pharmacological therapy, including antipsychotics and mood stabilizers, is the primary treatment approach for manic episode. The study aimed to analyze prescribing patterns over a 14-year period for patients with bipolar mania discharged from a psychiatric hospital in Taiwan. Patients with bipolar mania discharged from the study hospital between 2006 and 2019 (nâ =â 2956) were included in the analysis. Prescribed drugs for the treatment of manic episode, included mood stabilizers (i.e., lithium, valproate, carbamazepine) and any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs). Monotherapy, simple polypharmacy, and complex polypharmacy were also examined. Simple polypharmacy was defined as being prescribed 2 different bipolar drugs (lithium, valproate, carbamazepine, and any antipsychotics), while complex polypharmacy at least 3 bipolar drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. The prescription rates of valproate, SGAs, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, FGAs, and simple polypharmacy significantly decreased. Prescription rates of lithium and monotherapy did not significantly change. The study highlights the shifts in prescribing practices for bipolar mania. SGAs were prescribed more while FGAs declined, likely due to SGAs' favorable properties. Complex polypharmacy increased, reflecting the complexity of treating bipolar disorder. Long-term outcomes of these changes require further research.
Subject(s)
Antipsychotic Agents , Bipolar Disorder , Humans , Bipolar Disorder/drug therapy , Bipolar Disorder/psychology , Lithium/therapeutic use , Valproic Acid/therapeutic use , Mania , Hospitals, Psychiatric , Patient Discharge , Taiwan , Antipsychotic Agents/therapeutic use , Antimanic Agents/therapeutic use , Carbamazepine/therapeutic use , Anticonvulsants/therapeutic use , Benzodiazepines/therapeutic useABSTRACT
BACKGROUND/PURPOSE: 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. METHOD: 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%. RESULTS: 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. CONCLUSIONS: Among emerging technologies for lithium TDM, precision and accuracy remain a challenge, particularly for portable devices.
Subject(s)
Drug Monitoring , Humans , Drug Monitoring/methods , Antimanic Agents/therapeutic use , Lithium Compounds/therapeutic use , Lithium/therapeutic use , Lithium/bloodABSTRACT
More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome.
Subject(s)
Bipolar Disorder , Takotsubo Cardiomyopathy , Female , Humans , Lithium/therapeutic use , Takotsubo Cardiomyopathy/chemically induced , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/complications , Bipolar Disorder/drug therapy , Bipolar Disorder/complications , Antidepressive Agents/therapeutic use , Lithium Compounds/adverse effectsABSTRACT
El suicidio es un fenómeno que además de las pérdidas humanas que involucra, repercute negativamente en familiares y allegados, produciendo a su vez enormes gastos en el sistema sanitario. En Uruguay, la tasa de suicidio no solo ha experimentado un aumento sostenido, representando una preocupación constante para las autoridades, sino que suele ser una de la más altas de Latinoamérica, en 2022 fue de 23,08 cada 100.000 habitantes. Reconociendo que el suicidio es un fenómeno multifactorial grave, diversos estudios han indagado sobre la posible correlación entre la presencia de litio en agua corriente y tasas de suicidio, habiéndose observado una relación inversa, lo que permitiría considerar el litio como eventualmente protector de la conducta suicida. El presente estudio pretende abordar dicha correlación en los departamentos de Rocha y Montevideo, de Uruguay. Los resultados obtenidos no son concluyentes. En cuanto a las concentraciones de litio presentes en agua corriente, en general son menores a las señaladas en otros estudios como protectoras (30 µ/L). Es necesario profundizar en este eje de discusión, como en otros, para obtener un diagnóstico más detallado de este complejo y sentido fenómeno.
Suicide is a phenomenon that, in addition to the human losses it involves, has a negative impact on family members and acquaintances, leading to enormous costs in the healthcare system. In Uruguay, the suicide rate has not only experienced a sustained increase, representing a constant concern for authorities, but it also tends to be one of the highest in Latin America, reaching 23.08 per 100,000 inhabitants in 2022. Recognizing that suicide is a serious multifactorial phenomenon, several studies have investigated the possible correlation between the presence of lithium in tap water and suicide rates, noting an inverse relationship. This suggests that lithium could potentially be considered protective against suicidal behavior. This study aims to address this correlation in the departments of Rocha and Montevideo, Uruguay. The results obtained are inconclusive. Regarding the concentrations of lithium present in tap water, they are generally lower than those indicated in other studies as protective (30 µg/L). It is necessary to delve deeper into this axis of discussion, as in others, to obtain a more detailed diagnosis of this complex and profound phenomenon.
O suicídio é um fenómeno que, além das perdas humanas que envolve, tem um impacto negativo nos familiares e amigos, produzindo enormes gastos no sistema de saúde. No Uruguai, a taxa de suicídio não só tem registado um aumento sustentado, representando uma preocupação constante para as autoridades, mas geralmente é uma das mais altas da América Latina, sendo de 23,08 por 100.000 habitantes em 2022. Reconhecendo que o suicídio é um fenómeno multifatorial grave, vários estudos têm investigado a possível correlação entre a presença de lítio na água encanada e as taxas de suicídio; observa-se uma relação inversa, o que permitiria considerá-lo como um possível protetor do comportamento suicida. O presente estudo visa abordar esta correlação nos departamentos de Rocha e Montevidéu no Uruguai. Os resultados obtidos não são conclusivos. Quanto às concentrações de litio presentes na água corrente, são geralmente inferiores às indicadas em outros estudos como protetoras (30 µ/L). É necessário aprofundar esta área de discussão como em outras linhas de pesquisa, e obter um diagnóstico mais detalhado deste fenômeno complexo e significativo.
Subject(s)
Suicide , Drinking Water , Lithium/therapeutic use , Uruguay/epidemiologyABSTRACT
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
Subject(s)
Bipolar Disorder , Lithium , Humans , Lithium/pharmacology , Lithium/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/genetics , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/genetics , Genome-Wide Association Study , Multiomics , Focal AdhesionsABSTRACT
The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed pre-clinical and clinical studies that evidenced the neuroprotective effects of lithium in Alzheimer's (AD) and Parkinson's disease (PD). We followed the PRISMA guidelines and performed the systematic literature search using PubMed, EMBASE, Web of Science, and Cochrane Library. A total of 32 articles were identified. Twenty-nine studies were performed in animal models and 3 studies were performed on human samples of AD. A total of 17 preclinical studies were included in the meta-analysis. Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-ß and tau levels and significantly improved cognitive behavior in animal models of AD. Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model. Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients. This study lends further support to the idea of lithium's therapeutic potential in neurodegenerative diseases.