Lithium Treatment Research Articles

Lithium Treatment May Reduce Risk of Osteoporosis in Bipolar Patients

Lippincott's Bone and Joint Newsletter: September 2022 - Volume 28 - Issue 8 - p 91-92 doi: 10.1097/01.BONEJ.0000872700.67895.67

ECT for Depression May Cut Suicide Risk by Nearly 50%

Back to table of contents Previous article Next article Clinical & ResearchFull AccessECT for Depression May Cut Suicide Risk by Nearly 50%Nick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:22 Aug 2022https://doi.org/10.1176/appi.pn.2022.09.7.20AbstractThe study also found that suicide risk reduction was more pronounced in patients with unipolar depression than in patients with bipolar depression.Patients hospitalized for depression who received electroconvulsive therapy (ECT) had a nearly 50% reduced risk of suicide death over the following year versus comparable patients who did not receive ECT. The findings came from a detailed analysis of over 67,000 hospital records from patients seen in psychiatric inpatient units across Ontario, Canada.The analysis, published in Lancet Psychiatry, also found that patients who received ECT were less likely to die from other causes within one year after discharge.The findings provide further evidence that ECT can be a lifesaving treatment for patients with severe depression, said lead author Tyler Kaster, M.D., Ph.D., an assistant professor of psychiatry at the University of Toronto and medical head at the Temerty Centre for Therapeutic Brain Intervention.Kaster and colleagues used Canadian registries to examine the 12-month mortality outcomes of all adults aged 18 and older in Ontario who spent more than three days hospitalized for unipolar or bipolar depression between April 1, 2007, and December 31, 2017. Individuals were included in the analysis multiple times if their hospitalizations occurred more than 12 months apart. The final sample included 67,327 hospital admissions, during which 4,982 patients received ECT.A total of 450 deaths from suicide occurred within 12 months of discharge from the hospital; this included the deaths of 27 people who received ECT (5.84 per 1,000 person-years) and 423 who did not receive ECT (7.26 per 1,000 person-years).After adjusting for more than 100 demographic and medical variables that might influence whether a hospitalized patient would be a good candidate for ECT (such as age, psychotic symptoms, and physical comorbidities), the researchers found that patients who received ECT in the hospital had a 47% reduced risk of suicide death and a 25% reduced risk of any death over 12 months compared with those who did not receive ECT. Additional analysis revealed that suicide risk reduction was more pronounced in patients with unipolar depression than in patients with bipolar depression.Kaster and colleagues estimated that for every 200 hospitalized patients treated with ECT, one suicide will be prevented, which is about the same benefit seen with lithium treatment among people with bipolar disorder. Kaster said that while the number of suicides prevented by ECT may appear low, it is meaningful as suicide is a very rare event.Kaster noted that previous research he conducted also found no evidence that patients hospitalized for depression who received ECT were at an increased risk of serious medical events, compared with patients who did not receive ECT.While ECT is not for every depressed patient, Kaster said he hoped that the medical event and mortality data would provide further support that ECT is a medically safe procedure.“[ECT] is still the most invasive treatment for depression we have and any decision to proceed has to be made very thoughtfully, weighing all the benefits and risks,” he said.This study was supported by the Canadian Institutes for Health Research, Norris Scholars Award, and University of Toronto. ■Resources“Risk of Suicide Death Following Electroconvulsive Therapy Treatment for Depression: a Propensity Score-Weighted, Retrospective Cohort Study in Canada”“Risk of Serious Medical Events in Patients With Depression Treated With Electroconvulsive Therapy: A Propensity Score-Matched Retrospective Cohort Study” ISSUES NewArchived

Chronic Kidney Disease and Severe Mental Illness: Addressing Disparities in Access to Health Care and Health Outcomes.

Individuals with severe mental illness, including conditions such as schizophrenia and bipolar disorder, are at a higher risk of developing CKD. Higher incidences of CKD in this population can be partially explained by known risk factors, such as the use of lithium treatment and higher rates of cardiovascular disease. However, this does not fully explain the higher proportion of CKD in individuals with severe mental illness, and further research investigating the factors influencing disease onset and progression is needed. Similarly, although it is well documented that mental health difficulties, such as depression and anxiety, are highly prevalent among individuals with CKD, there is a lack of published data regarding the rates of severe mental illness in individuals with CKD. Furthermore, for individuals with CKD, having severe mental illness is associated with poor health outcomes, including higher mortality rates and higher rates of hospitalizations. Evidence also suggests that individuals with severe mental illness receive suboptimal kidney care, have fewer appointments with nephrologists, and are less likely to receive a kidney transplant. Limited research suggests that care might be improved through educating kidney health care staff regarding the needs of patients with severe mental illness and by facilitating closer collaboration with psychiatry. Further research investigating the rates of severe mental illness in patients with CKD, as well as the barriers and facilitators to effective care for this population, is clearly required to inform the provision of appropriate supports and to improve health outcomes for individuals with CKD and co-occurring severe mental illness.

Provider Perspectives on the Current Use of Lithium Medications and Lithium Monitoring Practices for Psychiatric Conditions.

PurposeDespite lithium being a gold standard treatment for bipolar disorder, the percentage of patients with bipolar disorder who are prescribed lithium medication has declined in many parts of the world over the past two decades. The use of lithium is limited by its narrow therapeutic window and adverse side effects, which necessitates frequent serum lithium monitoring; hence, there is a critical need for improved ways to monitor lithium levels in psychiatric patients. We have recently shown that saliva lithium levels are highly correlated with those in blood, thereby presenting an alternative to venipuncture. Saliva sampling could open the door for at-home collections – potential that has been exemplified throughout the COVID-19 pandemic – thereby allowing samples to be collected remotely and delivered to a specific site for testing. In addition, prototype point-of-care devices have been developed by others for serum lithium monitoring, suggesting potential for a saliva lithium monitoring device. Our objective was to query the perspectives of American psychiatrists on lithium treatment practices and obstacles, the potential for at-home saliva collection and point-of-care devices, for lithium monitoring, as an alternative to pathology-based blood testing.MethodsData was collected through an online, anonymous survey, distributed to American psychiatric societies.ResultsSixty-five respondents from 21 American states completed the survey. The majority of respondents were female, over 65 years of age, and/or had practiced for 30 years or more. The most frequent obstacles encountered with regard to lithium monitoring were adverse drug effects, and the need for monitoring. Overall, respondents believed saliva lithium monitoring and point-of-care devices would be useful, however raised concerns regarding validity and time-delay.ConclusionPoint-of-care devices and saliva lithium monitoring are promising alternatives to blood testing that would be welcomed by psychiatric societies, however, require extensive development and validation before implementation into a clinical setting.

Decreased miR-15b-5p/miR-155-5p levels and increased miR-134-5p/miR-652-3p levels among BD patients under lithium treatment

BackgroundThere is an increasing interest about the role of miRNAs in the pathogenesis of bipolar disorder (BD). In this study, we aimed to examine the role of miRNAs as potential diagnostic and clinical biomarkers in BD. MethodsFifteen miRNAs in plasmas obtained from BD patients (n = 66) and from the healthy control group (n = 66) were analyzed by a qPCR test. Clinical variables including lithium treatment response were assessed with various test batteries. The correlation of the miRNA levels with the clinical variables and scale scores was examined. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DIANA-miRPath v.3.0 software to identify the possible target genes. ResultsThe miR-132, miR-134, miR-152, miR-607, miR-633, and miR-652 levels were significantly increased, whereas the miR-15b and miR-155 levels were found to be significantly decreased in the patient group compared to the controls. The miR-15b-5p and miR-155-5p levels and increases in the miR-134-5p and miR-652-3p levels were calculated to have 83.3 % sensitivity and 78.8 % specificity in determining the risk of BD. miR-155-5p was associated with the disease burden and severity. Fatty acid biosynthesis and metabolism, viral carcinogenesis, the EBV infection, and extracellular matrix and adhesion pathways were highlighted as target pathways. ConclusionWe can conclude that miRNAs may play a role in the pathophysiology of BD through various biological pathways and that miRNAs may be used as a screening test to distinguish bipolar patients from healthy controls. Our findings will provide a basis for long-term follow-up studies with larger samples.

Cellular Genome-wide Association Study Identifies Common Genetic Variation Influencing Lithium-Induced Neural Progenitor Proliferation

BackgroundBipolar disorder is a highly heritable neuropsychiatric condition affecting more than 1% of the human population. Lithium salts are commonly prescribed as a mood stabilizer for individuals with bipolar disorder. Lithium is clinically effective in approximately half of treated individuals, and their genetic backgrounds are known to influence treatment outcomes. While the mechanism of lithium’s therapeutic action is unclear, it stimulates adult neural progenitor cell proliferation, similar to some antidepressant drugs. MethodsTo identify common genetic variants that modulate lithium-induced proliferation, we conducted an EdU incorporation assay in a library of 80 genotyped human neural progenitor cells treated with lithium. These data were used to perform a genome-wide association study to identify common genetic variants that influence lithium-induced neural progenitor cell proliferation. We manipulated the expression of a putatively causal gene using CRISPRi/a (clustered regularly interspaced short palindromic repeats interference/activation) constructs to experimentally verify lithium-induced proliferation effects. ResultsWe identified a locus on chr3p21.1 associated with lithium-induced proliferation. This locus is also associated with bipolar disorder risk, schizophrenia risk, and interindividual differences in intelligence. We identified a single gene, GNL3, whose expression temporally increased in an allele-specific fashion following lithium treatment. Experimentally increasing the expression of GNL3 led to increased proliferation under baseline conditions, while experimentally decreasing GNL3 expression suppressed lithium-induced proliferation. ConclusionsOur experiments reveal that common genetic variation modulates lithium-induced neural progenitor proliferation and that GNL3 expression is necessary for the full proliferation-stimulating effects of lithium. These results suggest that performing genome-wide associations in genetically diverse human cell lines is a useful approach to discover context-specific pharmacogenomic effects.

Lithium and Stroke Recovery: A Systematic Review and Meta-Analysis of Stroke Models in Rodents and Human Data.

Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.

Rationale and design of the prevention of paclitaxel-related neurological side effects with lithium trial - Protocol of a multicenter, randomized, double-blind, placebo- controlled proof-of-concept phase-2 clinical trial.

IntroductionChemotherapy-induced polyneuropathy (CIPN) and post-chemotherapy cognitive impairment (PCCI) are frequent side effects of paclitaxel treatment. CIPN/PCCI are potentially irreversible, reduce quality of life and often lead to treatment limitations, which affect patients’ outcome. We previously demonstrated that paclitaxel enhances an interaction of the Neuronal calcium sensor-1 protein (NCS-1) with the Inositol-1,4,5-trisphosphate receptor (InsP3R), which disrupts calcium homeostasis and triggers neuronal cell death via the calcium-dependent protease calpain in dorsal root ganglia neurons and neuronal precursor cells. Prophylactic treatment of rodents with lithium inhibits the NCS1-InsP3R interaction and ameliorates paclitaxel-induced polyneuropathy and cognitive impairment, which is in part supported by limited retrospective clinical data in patients treated with lithium carbonate at the time of chemotherapy. Currently no data are available from a prospective clinical trial to demonstrate its efficacy.Methods and analysisThe PREPARE study will be conducted as a multicenter, randomized, double-blind, placebo-controlled phase-2 trial with parallel group design. N = 84 patients with breast cancer will be randomized 1:1 to either lithium carbonate treatment (targeted serum concentration 0.5–0.8 mmol/l) or placebo with sham dose adjustments as add-on to (nab-) paclitaxel. The primary endpoint is the validated Total Neuropathy Score reduced (TNSr) at 2 weeks after the last (nab-) paclitaxel infusion. The aim is to show that the lithium carbonate group is superior to the placebo group, meaning that the mean TNSr after (nab-) paclitaxel is lower in the lithium carbonate group than in the placebo group. Secondary endpoints include: (1) severity of CIPN, (2) amount and dose of pain medication, (3) cumulative dose of (nab-) paclitaxel, (4) patient-reported symptoms of CIPN, quality of life and symptoms of anxiety and depression, (5) severity of cognitive impairment, (6) hippocampal volume and changes in structural/functional connectivity and (7) serum Neurofilament light chain protein concentrations.Ethics and disseminationThe study protocol was approved by the Berlin ethics committee (reference: 21/232 – IV E 10) and the respective federal agency (Bundesinstitut für Arzneimittel und Medizinprodukte, reference: 61-3910-4044771). The results of the study will be published in peer-reviewed medical journals as well as presented at relevant (inter)national conferences.Clinical trial registration[https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027165], identifier [DRKS00027165].

Magnetic field effects in biology from the perspective of the radical pair mechanism.

Hundreds of studies have found that weak magnetic fields can significantly influence various biological systems. However, the underlying mechanisms behind these phenomena remain elusive. Remarkably, the magnetic energies implicated in these effects are much smaller than thermal energies. Here, we review these observations, and we suggest an explanation based on the radical pair mechanism, which involves the quantum dynamics of the electron and nuclear spins of transient radical molecules. While the radical pair mechanism has been studied in detail in the context of avian magnetoreception, the studies reviewed here show that magnetosensitivity is widespread throughout biology. We review magnetic field effects on various physiological functions, discussing static, hypomagnetic and oscillating magnetic fields, as well as isotope effects. We then review the radical pair mechanism as a potential unifying model for the described magnetic field effects, and we discuss plausible candidate molecules for the radical pairs. We review recent studies proposing that the radical pair mechanism provides explanations for isotope effects in xenon anaesthesia and lithium treatment of hyperactivity, magnetic field effects on the circadian clock, and hypomagnetic field effects on neurogenesis and microtubule assembly. We conclude by discussing future lines of investigation in this exciting new area of quantum biology.

What affects chronic lithium poisoning in psychiatric patients? - a case report

INTRODUCTION: Despite medical developments, drug poisoning still occurs. Lithium is a drug that has been used for more than 60 years as a mood stabilizer in the treatment and prevention of bipolar disorder, mania and recurrent depression. Lithium is the most commonly prescribed mood stabilizer. It has a narrow therapeutic index. Its target concentration in acute mania should be 0.6-1.5 mEq/L and 0.6-0.8 mEq/L for maintenance therapy. Because of this, there is a risk of lithium intoxication. We would like to present to you the case of a patient with chronic lithium poisoning.
 MATERIALS AND METHOD: Patient information was collected from hospital records available in the clinical toxicology department. In addition, we conducted a literature review on lithium treatment, its toxicity, side effects and pharmacokinetics using PubMed.
 CASE REPORT: The patient, 58, was referred for lithium poisoning and admitted to the Clinical Toxicology and Cardiology Department in Lublin for treatment. The patient had a previous diagnosis of bipolar affective disorder, hypertension and obesity. According to the history, the patient was admitted to the psychiatric ward due to deterioration of her mental state for a month. She was found to have a high lithium level -2.98 mmol/L and elevated renal function parameters-creatinine 2.13 mg/dl. During treatment with hemodialysis, these parameters returned to normal.
 CONCLUSION: It is important to remember that lithium has a narrow therapeutic range. Attention should be paid during lithium treatment to situations that increase the risk of adverse effects and the development of toxicity, and serum lithium concentrations should be monitored during treatment.

Lithium treatment promotes the activation of primordial follicles through PI3K/Akt signaling†.

In mammals, dormant primordial follicles represent the ovarian reserve throughout reproductive life. In vitro activation of dormant primordial follicles has been used to treat patients with premature ovarian insufficiency (POI). However, there remains a lack of effective strategies to stimulate follicle activation in vivo. In this study, we used an in vitro ovarian culture system and intraperitoneal injection to study the effect of lithium treatment on primordial follicle activation. Lithium increased the number of growing follicles in cultured mouse ovaries and promoted pre-granulosa cell proliferation. Furthermore, lithium significantly increased the levels of phosphorylated protein kinase B (Akt) and the number of oocytes with forkhead Box O3a (FOXO3a) nuclear export. Inhibition of the phosphatidylinositol 3 kinase (PI3K)/Akt pathway by LY294002 reversed lithium-promoted mouse primordial follicle activation. These results suggest that lithium promotes mouse primordial follicle activation by the PI3K/Akt signaling. Lithium also promoted primordial follicle activation and increased the levels of p-Akt in mouse ovaries in vivo and in human ovarian tissue cultured in vitro. Taken together, lithium promotes primordial follicle activation in mice and humans by the PI3K/Akt signaling. Lithium might be a potential oral drug for treating infertility in POI patients with residual dormant primordial follicles.

Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D1 receptor dependent mechanism

Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic- and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateperone, electrophysiology in vitro to study lumateperone's effects on NMDA- and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine- and glutamate release in the rat mPFC. Our results demonstrate that lumateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumateperone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations.

Effect of chronic lithium on mechanical sensitivity and trabecular bone loss induced by type-1 diabetes mellitus in mice.

Type-1 diabetes mellitus (T1DM) is a chronic condition characterized by long-term hyperglycemia that results in several complications such as painful peripheral neuropathy, bone deterioration, and increased risk of bone fractures. Lithium, a first-line therapy for bipolar disorder, has become an attractive agent for attenuating peripheral neuropathy and menopause-induced bone loss. Therefore, our aim was to determine the effect of chronic lithium treatment on mechanical hypersensitivity and trabecular bone loss induced by T1DM in mice. T1DM was induced in male C57BL/6J mice by intraperitoneal injection of streptozotocin (STZ, 50mg/kg/day, for 5 consecutive days). 12 weeks after T1DM-induction, mice received a daily intraperitoneal injection of vehicle, 30 or 60mg/kg lithium (as LiCl) for 6 weeks. Throughout the treatment period, blood glucose levels and mechanical sensitivity were evaluated every 2 weeks. After lithium treatment, the femur and L5 vertebra were harvested for microcomputed tomography (microCT) analysis. T1DM mice showed significant hyperglycemia, mechanical hypersensitivity, and significant trabecular bone loss as compared with the control group. Chronic lithium treatment did not revert the hindpaw mechanical hypersensitivity nor hyperglycemia associated to T1DM induced by STZ. In contrast, microCT analysis revealed that lithium reverted, in a dose-dependent manner, the loss of trabecular bone associated to T1DM induced by STZ at both the distal femur and L5 vertebra. Lithium treatment by itself did not affect any trabecular bone parameter in non-diabetic mice.

Antidepressant chronotherapeutics normalizes prefrontal 1H-MRS glutamate in bipolar depression

BackgroundDysfunctional glutamatergic neurotransmission has been proposed both, as a biological underpinning of mood disorder and as a target for rapid-acting antidepressant treatments. Total sleep deprivation and light therapy (TSD + LT) can prompt antidepressant response in drug-resistant bipolar depression. Here we explored the effects of TSD + LT on dorsolateral prefrontal cortex (DLPFC) glutamate and/or glutamine+glutamate (Glx) levels. MethodsWe studied single voxel 1H-MRS measures of DLPFC Glu and Glx levels of 48 healthy participants and 55 inpatients with a major depressive episode in course of Bipolar Disorder, a subset of which (N = 23) underwent three cycles of repeated TSD + LT and were evaluated before and after treatment. Treatment effects of mood and on Glu and Glx concentrations were analyzed in the context of the Generalized Linear Model (GLM), correcting for age, sex and ongoing lithium treatment. ResultsHigher concentration of Glu (adjusted Z = −2189, p = 0,0285) and Glx (adjusted Z = −3,13, p = 0,0017) were observed in BD patients compared to HC. Treatment caused a significant rapid reduction of depressive symptom severity over time (F = 63.98, p < 0.01). Change in depression levels after TSD + LT treatment was significantly influenced by delta change in Glu levels (LR χ2 = 4.619, p = 0.0316) and in Glx levels (LR χ2 = 4.486, p = 0.0341). ConclusionA reduction in Glu and Glx levels associated with depression could contribute to the mechanism of action of TSD + LT, directly acting on glutamatergic neurons, or to the interaction between the glutamatergic system and dopamine (DA) and serotonin (5-HT) levels, known to be targeted by TSD. This is in line with several studies showing a glutamatergic modulation effects of antidepressants and mood stabilizing agents. This finding deepens our understanding of antidepressant effect of chronoterapeutics.

Comparison of Alternative Application Methods for Anti-Varroa Lithium Chloride Treatments.

Simple SummaryThe Varroa mite is one of the most dangerous pests of honey bee colonies, spreading many diseases, and its high infestation rate leads to the death of the colony. Due to its wide-scale distribution and lethal effect, this mite parasite threatens not only the honey industry but also the pollination of many plant species, including several cultivated plants. Therefore, an uncontrolled varroosis could threaten the human food supply as well as trigger biodiversity loss. Control options against Varroa are still inadequate; the mite could develop resistance to synthetic chemicals, whereas the efficiency of organic acid and essential oils-based treatments is very variable. Recently, lithium has been identified as a potential and effective anti-Varroa agent with both systematic and contact modes of action. Present experiments revealed that the efficiency of the lithium treatment depends greatly on the application method. The trickling method of application in repeated treatment and concentration of 500 mM provided very high, >>90%, efficiency. However, further investigations are required before the lithium chloride could be registered as a veterinary medicine in beekeeping practice.Varroosis is one of the most dangerous threats to the bee industry but means of its treatment are still unsatisfactory. Lithium-based anti-Varroa treatments may provide an alternative, as this trace element can be a natural component of honey and is well tolerated by adult bees. However, it can be toxic to larvae and its use in beekeeping practice is not yet well understood. The present study aimed to investigate the efficacy of relevant application methods of acaricides used in beekeeping practice in brood-free conditions for lithium. Vaporisation proved to be an inefficient method of lithium treatment and killed only 9.9 ± 3.3% (mean ± SD) of mites in the hive. Lithium-impregnated paper strips showed moderate efficiency by killing 55.1 ± 26.2% of mites. The most effective way of applying lithium was the trickling method; different trickling treatments decreased the abundance of mites on average by 65 to 99.7%, depending on the applied dosage and the number of treatments. Repeated trickling treatments were more effective than single treatments, and they generally provided >90% efficiency. Experiments also proved that adding sugar to the trickling solution does not influence treatment efficiency. Thus, it is suggested that repeated and sugar-free trickling treatments with moderate lithium dosage could be the most rational methodology. Since lithium is not yet legalised in beekeeping practice, comprehensive studies are also needed to uncover the amount of lithium residue in bee products, depending on the treatment parameters.

¿Se Podrá Recomendar el Tratamiento con Litio Para el Deterioro Cognitivo Leve y la Demencia por Enfermedad de Alzheimer? Falta Evidencia Sobre su Eficacia y su Seguridad: Revisión Sistemática y Metanálisis

IntroductionAlzheimer's disease is the most prevalent neurodegenerative disease worldwide. Currently available treatments are scarce and have modest effects. Lithium has been shown to decrease cognitive impairment in people with bipolar affective disorder. However, studies evaluating lithium for cognitive impairment in Alzheimer's disease remain controversial. MethodsWe conducted a systematic search of the literature using PubMed, EMBASE, the Cochrane Library, LILACS, and Google Scholar between 30 April and 10 May 2021. Randomised controlled clinical trials (RCTs) conducted to evaluate the efficacy and safety of lithium as a treatment for cognitive impairment in people with dementia and mild cognitive impairment due to Alzheimer's disease were included. The primary outcome was the difference in cognitive functioning at the end of the study. Two authors selected the studies and extracted the data. We calculated the standardised mean differences (SMD) for continuous variables and the relative risk (RR) for dichotomous variables. Review Manager 5.4 software was used for data processing. Results2,078 reports were identified and 3 studies with data from 248 participants were included. A fourth report was included for safety analysis. Compared to placebo, no significant difference was found in the cognitive performance of patients with mild cognitive impairment or dementia due to Alzheimer's disease receiving lithium treatment (SMD=–0.39; 95%CI, –0.82 to 0.04; I2=53%; n=195). Also, significant differences were not found in the rate of discontinuation for any cause (RR=0.90; 95%CI, 0.46-1.78; I2=0%), and the rate of adverse effects between lithium and placebo (RR=1.29; 95%CI, 0.83-2.03; I2=0%). ConclusionsThe current evidence is insufficient to assume any effect of lithium as a treatment for cognitive impairment in Alzheimer's disease dementia. It is necessary to continue building better quality studies to justify the use of lithium in this population in clinical practice. Given the toxicity of lithium, adequate pre-selection of patients and close monitoring should be ensured.

Lithium use during breastfeeding was safe in healthy full-term infants under strict monitoring.

Previous studies on breastfeeding during lithium therapy have shown conflicting results. The aim of this study was to evaluate the safety when practising thorough follow-up of the infants. This retrospective study focused on women with lithium medication, and their breastfed infants born between 2006 and 2021 in Stockholm, Sweden. Information about infant serum lithium concentrations and clinical status was collected from medical records. In total, 30 infants exposed to lithium through breastmilk, 21 girls and 9 boys, were included. The median age at follow-up was 40 days (range 8-364 days). The median lithium serum concentration was 0.10 mmol/L in the second week of life (range <0.05-0.7 mmol/L), 0.08 in week 2-4 (range <0.05-1.2), 0.06 in the second month of life (range <0.05-0.2) and 0.07 after 2 months of age (range <0.05-0.2). Unexpectedly high lithium concentrations were found in two infants in the first month of life. Apart from poor weight gain, no adverse effects were found. Serum lithium concentrations in breastfed infants were stabilised at barely measurable levels after the first weeks of life. Before that, concentrations higher than the mothers were found. Lithium treatment during breastfeeding can be considered safe under strict follow-up.

The potentially protective effect of lithium on the risk of osteoporosis: A nationwide study of 22,912 patients with bipolar disorder

IntroductionOsteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, has been suggested to be particularly common among individuals with bipolar disorder. Lithium, a mood-stabilizer used as first-line treatment for bipolar disorder, may have bone-protecting properties.ObjectivesWe aimed to subject both of these hypotheses to further examination in a nationwide register-based study.MethodsWe compared the incidence of osteoporosis, identified via hospital discharge diagnoses and prescribed medications, between all individuals diagnosed with bipolar disorder and age- and sex-matched controls from the general population (earliest start of follow-up at the age of 40 years) using Cox regression. Subsequently, we followed the patients with bipolar disorder and identified all prescriptions for mood-stabilizing medications. Using Cox regression, we compared the incidence of osteoporosis for patients using lithium, antipsychotics or anticonvulsants, respectively, with that of patients not using these medications.ResultsWe followed 22,912 patients with bipolar disorder (median age 50.4 years, 43.4% men) and 114,560 matched controls for 1,215,698 person-years. The incidence of osteoporosis per 1,000 person-years was 8.70 (95%CI:8.28-9.14) among patients with bipolar disorder and 7.84 (95%CI:7.67-8.01) among controls, resulting in a hazard rate ratio (HRR) of 1.15 (95%CI:1.09-1.21). Lithium treatment was associated with reduced risk of osteoporosis (HRR=0.62; 95%CI:0.53-0.72) in a treatment-duration-response-like manner. Treatment with antipsychotics and anticonvulsants was not associated with reduced risk of osteoporosis.ConclusionsThis is the first longitudinal study to show that the risk of osteoporosis is elevated among patients with bipolar disorder, and that treatment with lithium is associated with reduced risk of osteoporosis.DisclosureDr. Østergaard has received the 2020 Lundbeck Foundation Young Investigator Prize. Furthermore, SDØ owns units of mutual funds with stock tickers DKIGI, DKIDKIX, MAJGRO, NBIDE, SPIC20CAPK, SPVILRKL and WEKAFKI.

Evaluation of the relationship between lithium treatment response and suicide attempt in bipolar disorder

IntroductionSuicide risk is 20-30 fold higher in bipolar disorder(BD) than general population. A positive family history of suicide, early-onset bipolar disorder, rapid cycling, and drug/alcohol addiction have been identified as risk factors for non-fatal suicidal behavior. Lithium is the only mood stabilizer known to have a suicide-reducing effect in patients with BD. Less than half of the bipolar patients respond lithium well. Even though mechanism of action on suicide behavior is not clearly known, it is thought that lithium significantly reduces “impulsive-aggressive” behavior via serotonergic system which might also be related with treatment response in BD.ObjectivesThe aim of this study is to evaluate the relationship between lithium response and history of suicide.MethodsThose who scored 7 points or more from the Alda total score were considered good responders. Patients were divided into those who responded well to lithium treatment and those who did not. History of suicide attemptbetween these two groups was compared.Results65.3% of the patients were female (n:49). The mean age of the patients was 36.82±13.35 years. 25 patients responded well to lithium treatment. Among the good responders, 32% of the patients and 25% of the non-responders had a history of suicide attempts. This difference was not statistically significant. (p=0.46 x²=0.13)ConclusionsThe insufficient number of data in the study was considered as a limitation of this study. In addition, there is a need for more studies as there are many factors that cause suicide attempts.DisclosureNo significant relationships.

Bipolar disorders and suicide: stumbling twice with the same stone?

IntroductionSuicide is the most terrible outcome of bipolar disorders (BD). It impacts families and healthcare professionals deeply. Family history of suicide (FHS) is one of its main risk factors, whereas lithium treatment and absence of substance use disorders (SUD) are two of its few modifiable protective factors.ObjectivesTo explore the relationship between FHS and clinical characteristics in BD. We hypothesized that FHS would be associated with less SUD, higher rates of lithium treatment and shorter duration of untreated illness (DUI).MethodsCross-sectional analysis of subjects with BD followed-up in a specialised outpatient unit (Barcelona, October’08-March’18). We described data with measures of frequency, central tendency and dispersion, and we used χ², Fisher’s test and t-tests for comparisons.ResultsThe sample consisted of 83 subjects, 56.6% males, mean age 41.9 years (SD 12.7). 74.7% (n=62) had a diagnosis of BD-I and 25.3% (n=21) of BD-II. 11 subjects (13.3%) had FHS. Those with FHS did not show significant differences in sociodemographic data, DUI (58.5+/-60.4 vs 38.19+/-84.9 months, p=0.341), lithium use (72.7% vs 73.6%, p=0.95) or SUD (27.3% vs 23.6%, p=0.79). There were differences in terms of lifetime suicide attempts (54.5% vs 20.8%, p=0.026), family history of mental disorders (100% vs 69.4%, n=0.032).ConclusionsContrary to our hypothesis, FHS was not associated with the modifiable protective factors against suicide (namely, less SUD and more lithium prescription). Similarly, we did not find an association with earlier access to mental health services at symptom onset (DUP as proxy). Therefore, our results suggest FHS does not modify attitudes towards prevention.DisclosureNo significant relationships.