Dose Of Lithium Research Articles

Exploring the clinical factors affecting lithium dose and plasma level and the effect of brand.

Optimal use of lithium involves adjustment of the dose, to keep the plasma level within the narrow, recommended range. Brand-specific prescribing has long been considered critical to achieving this aim, but this is a convention based on very limited data. To explore the effect of selected demographic and clinical factors on the relationship between lithium dose and plasma level and determine whether there is an independent effect of lithium brand. Analysis of clinical audit data collected in 2023 as part of a quality improvement programme addressing the use of lithium, conducted by the Prescribing Observatory for Mental Health. Data were collected from clinical records using a bespoke proforma, submitted online and analysed using SPSS. Data were submitted for 4405 patients who had been prescribed solid-dosage formulations of lithium for more than a year. Priadel® was prescribed for 3722 (84%) of these patients, Camcolit® for 112 (2.5%) and the prescription was written generically for 554 (12.5%). Compared with Priadel, where Camcolit was prescribed, the mean daily dose was 10% higher and the mean plasma lithium level was 11% higher. A multivariable analysis was conducted to explore the relationship between selected clinical variables and maintenance lithium dose. This found that in 4213 patients whose most recent plasma lithium level was between 0.3 and 1.19 mmol/L, the variables age, sex, ethnicity, psychiatric diagnosis and the severity of chronic kidney disease were independently associated with dose while the brand of lithium prescribed was not. Our findings replicate those of previous studies with respect to the demographic and clinical variables that can be expected to influence lithium dosage in routine clinical practice. This reinforces the need to titrate the dosage for each individual patient, to achieve and maintain the target plasma level. However, the findings suggest that the Priadel and Camcolit brands of lithium are essentially interchangeable.

Management of Lithium Dosing Around Delivery: An Observational Study.

Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes. In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available. There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes. Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.Appeared originally in Bipolar Disord 2021; 23:49-54.

External Evaluation of Population Pharmacokinetics Models of Lithium in the Bipolar Population.

Lithium has been used in the treatment of bipolar disorder for several decades. Treatment optimization is recommended for this drug, due to its narrow therapeutic range and a large pharmacokinetics (PK) variability. In addition to therapeutic drug monitoring, attempts have been made to predict individual lithium doses using population pharmacokinetics (popPK) models. This study aims to assess the clinical applicability of published lithium popPK models by testing their predictive performance on two different external datasets. Available PopPK models were identified and their predictive performance was determined using a clinical dataset (46 patients/samples) and the literature dataset (89 patients/samples). The median prediction error (PE) and median absolute PE were used to assess bias and inaccuracy. The potential factors influencing model predictability were also investigated, and the results of both external evaluations compared. Only one model met the acceptability criteria for both datasets. Overall, there was a lack of predictability of models; median PE and median absolute PE, respectively, ranged from -6.6% to 111.2% and from 24.4% to 111.2% for the literature dataset, and from -4.5% to 137.6% and from 24.9% to 137.6% for the clinical dataset. Most models underpredicted the observed concentrations (7 out of 10 models presented a negative bias). Renal status was included as a covariate of lithium's clearance in only two models. To conclude, most of lithium's PopPK models had limited predictive performances related to the absence of covariates of interest included, such as renal status. A solution to this problem could be to improve the models with methodologies such as metamodeling. This could be useful in the perspective of model-informed precision dosing.

Effects of lithium on locomotor activity and circadian rhythm of honey bees

Lithium has been considered a potential acaricidal agent against the honey bee (Apis mellifera) parasite Varroa. It is known that lithium suppresses elevated activity and regulates circadian rhythms and light response when administered to humans as a primary therapeutic chemical for bipolar disorder and to other bipolar syndrome model organisms, given the crucial role of timing in the bee's foraging activity and the alternating sunlight vs dark colony environment bees are exposed, we explored the influence of lithium on locomotor activity (LMA) and circadian rhythm of honey bees. We conducted acute and chronic lithium administration experiments, altering light conditions and lithium doses to assess LMA and circadian rhythm changes. We fed bees one time 10 μl sucrose solution with 0, 50, 150, and 450 mM LiCl in the acute application experiment and 0, 1, 5, and 10 mmol/kg LiCl ad libitum in bee candy in the chronic application experiment. Both acute and chronic lithium treatments significantly decreased the induced LMA under constant light. Chronic lithium treatment disrupted circadian rhythmicity in constant darkness. The circadian period was lengthened by lithium treatment under constant light. We discuss the results in the context of Varroa control and lithium's effect on bipolar disorder.

Causes, clinical characteristics, and outcomes of high lithium levels and intoxications: Retrospective analysis of patient records.

The mood stabilizer lithium has a narrow therapeutic index with a relevant risk of intoxication. We used real-world hospital data to identify causes, treatment courses, and outcomes of high lithium levels and intoxications. Retrospective chart review of patients with a lithium concentration of ⩾1.1 mmol/L, who were treated at Charité University Medical Center Berlin. We identified 136 patients (58% women; mean age: 54.7 years) with high lithium levels or intoxication. 66.9% were chronic (stable lithium dose but changes in other variables such as co-medication). 40.4% took at least one risk medication with a relative contraindication for concurrent lithium treatment. 11.1% of the cases with a high therapeutic level showed moderate to severe intoxications. Feverish infections were significantly associated with severe intoxications. Overall, 97.1% (132/136) of patients fully recovered, two had residual but mild symptoms and two died during hospitalization (unlikely related to the intoxication). In 37.5% of patients, no psychiatrist was involved in the management of high lithium levels or intoxication. In these patients, lithium treatment was adjusted or discontinued in 37.3% of the cases compared to 64.7% when a psychiatrist was involved (χ²(1) = 9.683, p = 0.002). Patients and medical doctors should be aware of the increased risk of lithium intoxication already within the high therapeutic range and should consider alternative medications without relative contraindications for concurrent lithium use. Involving psychiatrists during or after an intoxication event is associated with more frequent adjustment of the maintenance lithium dose and should be considered in most cases.

Low and very low lithium levels: Thyroid effects are small but still require monitoring.

Low doses of lithium, as might be used for mood or dementia prevention, do not carry the same renal, toxicity, and tolerability problems of doses used for prophylaxis or treatment of mania. However, thyroid effects of low doses have not been investigated. Our goal in this study was to assess the changes in thyroid-stimulating hormone (TSH) associated with a broad range of lithium levels, including those well below the therapeutic range for bipolar disorders. This study was conducted in a small healthcare system with 19 associated primary care clinics served by a Collaborative Care program of psychiatric consultation. In this retrospective review of electronic records, we searched for patients who had received a lithium prescription and both pre- and post-lithium thyroid-stimulating hormone (TSH) levels. Patients with low lithium levels (<0.5 mEq/L, N = 197) had a mean thyroid-stimulating hormone (TSH) increase of 0.52 mIU/L. Patients with maintenance lithium levels (0.5-0.8 mEq/L; N = 123) had a mean TSH increase of 1.01 mIU/L; and patients with antimanic lithium levels (>0.8 mEq/L; N = 79) had a mean TSH increase of 2.16 mIU/L. The probability of TSH exceeding the upper limit of normal in our laboratory (>4.2 mIU/L) was positively associated with pre-lithium TSH. These results suggest that the risk of lithium-induced hypothyroidism is dose-related, and relatively small with very low doses, but thyroid monitoring, including a pre-lithium TSH, is still warranted.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran-Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation.

Folic acid supplementation improved cognitive deficits associated with lithium administration during pregnancy in rat offspring.

The present study aimed to analyse both neurobehavioural and biochemical results of neonates born of mothers exposed to different doses of lithium along with the groups that received lithium at the highest dose with folic acid as a preventive treatment. Male and female rats were mated in separate cages, and pregnant rats were divided into eight first group as (1) vehicle; (2) propylthiouracil (PTU)-induced hypothyroidism; (3-4) received two different doses of lithium carbonate (15 and 30 mg/kg); (5-7) the highest doses of lithium (30 mg/kg) plus three different doses of folic acid (5, 10 and 15 mg/kg); and (8) received just folic acid (15 mg/kg). All treatments were dissolved in drinking water and continued until delivery, followed by returning to a regular diet without treatment. Lithium (30 mg/kg) disrupts both behavioural and biochemical markers, including TSH, T3 and T4 as measuring indicators to assess thyroid function, IL-10 and TNF-α as anti-inflammatory and inflammatory agents, respectively, malondialdehyde as an oxidative stress marker, alongside SOD, and catalase activity as antioxidant indicators. Besides, folic acid, almost at the highest dose (15 mg/kg), attenuated memory impairement and anxiety-like behaviour caused by lithium. Moreover, the groups treated with folic acid alone in comparison with vehicles demonstrated higher levels of antioxidant and anti-inflammatory indicators. According to the results, prenatal exposure to a high dose of lithium (30 mg/kg) leads to foetal neurodevelopmental disorder and growth restriction through various mechanisms more likely attributed to hypothyroidism, which means it should be either prohibited or prescribed cautiously during pregnancy.

Lithium treatment versus hospitalization in bipolar disorder and major depression patients

BackgroundPreventing hospitalization of major affective disorder patients is a fundamental clinical challenge for which lithium is expected to be helpful. MethodsWe compared hospitalization rates and morbidity of 260 patients with DSM-5 bipolar or major depressive disorder in the 12 months before starting lithium versus 12 months of its use. We evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, lithium dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses. ResultsWithin 12 months before lithium, 40.4 % of patients were hospitalized versus 11.2 % during lithium treatment; other measures of morbidity also improved. Benefits were similar with bipolar and major depressive disorders. Independently associated with hospitalization during lithium treatment were: receiving an antipsychotic with lithium, suicide attempt during lithium treatment, lifetime substance abuse, and psychiatric hospitalization in the year before starting lithium, but not diagnosis. LimitationsParticipants and observation times were limited. The study was retrospective regarding clinical history, lacked strict control of treatments and was not blinded. ConclusionsThis naturalistic study adds support to the effectiveness of lithium treatment in preventing hospitalization in patients with episodic major mood disorders.

Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden

Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy. To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes. This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden. New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels. Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users. The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76). In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.

Voluntary wheel running and lithium supplementation improves muscle force production without altering SERCA function in the D2 mdx mouse

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle wasting disease that, with no cure, leads to early mortality (30-40 years of age). Previous studies have shown that voluntary wheel running can mitigate disease pathology and improve muscle contractility in the preclinical mdx mouse model. We have shown that treating wild-type (WT) mice with a low dose of lithium, a natural inhibitor of glycogen synthase kinase 3, enhanced soleus (SOL) and extensor digitorum longus (EDL) muscle contractility. Our objectives were to test our hypothesis of whether combining VWR with low dose lithium supplementation could provide further benefits to muscle contractility in DBA/2J mdx mice – a model that displays far worse disease severity compared with the traditional C57BL/10 mdx mouse. We also examined if this combined intervention could improve muscle calcium regulation in muscle by assessing sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) function as we have recently shown that SERCA function is drastically impaired in D2 mdx mice, which could also contribute to deficits in muscle force production. Methods: Young (5-6 week old) male D2 WT and mdx mice were ordered from Jackson Laboratory. D2 mdx mice were assigned into each of the following conditions: sedentary ( mdxSED), voluntary wheel running ( mdxVWR), or VWR+lithium chloride ( mdxVWR+Li). The VWR groups were given access to a cagewheel for a total of 6 weeks, and the mdxVWR+Li group were provided a low dose of LiCl (50 mg/kg/day) via drinking water for the entire duration of the study. After 6 weeks, all mice were euthanized and the SOL and EDL muscles were subjected to force-frequency curve analysis (1-160 Hz). SERCA function was assessed by performing SERCA activity assays and a Ca 2+ uptake assay. Results: In the SOL, the combined effect of lithium and VWR improved specific force production to near WT levels across submaximal and maximal frequencies. Specific force production in the mdxVWR+Li group was significantly greater compared to the mdxSED group at all stimulation frequencies. Rate of SOL force development was significantly lower in all mdx groups compared to WT. However, rate of relaxation was only significantly reduced (vs. WT) within the mdxSED group, suggesting that VWR and VWR+Li improved relaxation. This could not be explained by any changes in SERCA function. In the EDL, specific force was significantly (p&lt;0.001) reduced across mdx groups compared to WT; however, of all mdx groups, the mdxVWR+Li produced the most force and was significantly different compared to mdxVWR at 80 and 160 Hz. Rates of force development and relaxation were all slower in all mdx groups compared to WT, and there were no differences in SERCA activity. Conclusions: Combining lithium supplementation with VWR improved SOL and EDL force production in the D2 mdx mouse without any changes to SERCA function. V.A.F is a Tier 2 Canada Research Chair in Muscle Plasticity and Tissue-Remodelling. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effects of a varying doses of pilocarpine and lithium induced status epilepticus, and treatment with BPC-157

The effects of a varying doses of pilocarpine and lithium induced status epilepticus, and treatment with BPC-157

Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.

This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients. PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot. Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate. Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.

Accumulation lithium in the tissues and organs of goslings concerning of its level in the mixed feed

We studied the possibility of fortification of goslings’ products with lithium and peculiarities of its depositing in the organs and tissues of goslings concerning lithium level in the mixed feed. Experimental studies have been conducted on goose breed Legart. A total of 320 one-day-old goslings were divided on the principle of analogues into four groups and 80 heads each. The goslings of the first control group did not receive the lithium supplement with the feed mix. Experimental groups were fed with the feed mixed that additionally was supplemented with different doses of lithium by the scheme of the experiment. After 70 days of rearing, three birds were randomly selected from each group and their control slaughter. The lithium content in the representative samples of muscle tissue and organs of goslings was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). It was established that feeding the growing goslings with mixed feed containing lithium supplements in doses of 0.05, 0.1 and 0.15 mg/kg, contributed to the increase (P &lt; 0.001) of the concentration of this trace element in the muscles of the thigh and drumstick accordingly 789.5, 1589.5 and at 3447.4 %, in the muscles of the breast 1096.8, 2080.6 and at 3948.4 %, liver are 455.4, 824.6 and at 1440.8 % are compared to goslings that did not receive lithium supplements. Significantly high values of lithium accumulation factors in organs and tissues of gosling (3.21–14.44) indicated that this element has a substantial accumulating capacity. The meat of goslings enriched with lithium can be considered as a natural product with bio-corrective action that can be used in human nutrition. These meat products can be particularly useful for people that are living in regions with a low environmental level of lithium.

Lithium levels and lifestyle in patients with bipolar disorder: a new tool for self-management

BackgroundPatients should get actively involved in the management of their illness. The aim of this study was to assess the influence of lifestyle factors, including sleep, diet, and physical activity, on lithium levels in patients with bipolar disorder.MethodsA multicenter study was performed. In total, 157 lithium measurements were done biweekly in a sample of 65 patients (35 women) over 6 weeks. Lifestyle, based on total sleep hours and physical activity, was assessed by actigraphy. Diet was evaluated using the Mediterranean Lifestyle Index (Medlife).Results35.4% of patients had a normal weight. The mean Medlife score was 14.5 (± 2.5) (moderate-good adherence to Mediterranean diet). BMI, daily dose of lithium and intensity of physical activity had a combined effect on lithium levels, after adjustment for other variables. Patients who practiced intense physical exercise, who took lower doses and had a higher BMI exhibited lower levels of lithium.ConclusionsHigher physical activity and BMI contribute to lower lithium levels. Patients should be made aware of these relationships to improve their perception of control and self-management. Lifestyle-based interventions contribute to establishing a more personalized medicine.

Lithium management in pregnant patients with bipolar disorder

IntroductionWomen with bipolar disorder often ask their treating clinician for information about family planning, as they are concerned about the impact of their illness on offspring. Pregnancy places additional stress on patients, and physiological changes are particularly acute during postpartum. On the other hand, the risk of abnormalities and teratogenicity from psychotropic drugs is significant. The decision wether resuming or discontinuating lithium is discussed.ObjectivesWe present a theoretical review on the topic.MethodsA bibliographic review is presented.ResultsThe choice to continue medication during pregnancy balances the risks of an untreated illness with the risks of medication exposure. Abrupt discontinuation of psychotropic medications is associated with an increased risk for illness recurrence. Women with BD who discontinue their medications before or during pregnancy have a 71% risk of recurrence with new episodes occurring most frequently in the first trimester. Recurrent illness during pregnancy is associated with a 66% increase in the risk of postpartum episodes. Untreated or under-treated BD during pregnancy is associated with poor birth outcomes independent of pharmacotherapy exposure, including preterm birth, low birth-weight, intrauterine growth retardation, small for gestational age, fetal distress, and adverse neurodeve- lopmental outcomes. Women with untreated BD also have behavioral risk factors such as decreased compliance with prenatal care, poor nutrition, and high-risk behaviors. Impaired capacity to function may result in loss of employment, health care benefits, and social support. The biological and psychosocial risks of a BD episode are the justification for the risk of medication exposure.Fetal exposure to lithium has been associated with an increased risk for cardiac abnormalities. The risk for Ebstein’s anomaly with first trimester exposure is 1 (0.1%) to 2 in 1000 (0.2%), but the absolute risk remains low. Folate supplementation with 5 mg reduces the risk and severity of congenital heart disease. Lithium toxicity causes lethargy, hypotonia, tachycardia, coma, cyanosis, and chronic twitching in the newborn.Strategies to minimize fetal exposure and maintain efficacy include using the lowest effective dose, prescribing lithium twice daily to avoid high peak serum concentrations, and regular monitoring of lithium serum concentrations. The effective serum concentration must be established before pregnancy. If a therapeutic concentration has not been established, the lithium dose is titrated to a concentration within the therapeutic range. Breast feeding is discouraged in women taking lithium because of the high rate of transmission to the infant.ConclusionsTreatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy, especially during the first trimester, against its effectiveness at reducing relapse.Disclosure of InterestNone Declared

Effect of Regulated Add-on Sodium Chloride Intake on Stabilization of Serum Lithium Concentration in Bipolar Disorder: A Randomized Controlled Trial

IntroductionThe therapeutic use of lithium in bipolar disorder is often restricted due to its narrow therapeutic window and adverse drug reactions. Lithium-induced early renal dysfunction is clinically important as it may lead to sodium depletion due to natriuresis leading to lithium retention and lithium toxicity. This is most often seen in the initial phases of therapy, and psychiatrists struggle titrating the dose of lithium and stabilizing the serum lithium level.ObjectivesThe present study was conducted to evaluate the effect of add-on sodium chloride on serum lithium levels in bipolar disorder.MethodsThe present randomized controlled trial (NCT04222816) was conducted in 60 patients with type I bipolar disorder who were randomized into the control group who received lithium carbonate with the advice not to take additional salt (at the table) and the test group who received sachets of sodium chloride (1 g/d) as an add-on to lithium carbonate and were advised to restrict their additional salt intake (at the table) to 1 g/d. After baseline assessments, all patients were followed up at 4 weeks, 8 weeks, and 12 weeks when serum lithium, sodium and potassium were estimated. Serum creatinine and aldosterone were repeated at 12 weeks.ResultsIn the test group, the fluctuation rate in serum lithium (26.7%) was significantly (p=0.01) lower than in the control group (63.3%). There was a significant difference in serum lithium in the control group at different time points; however, the changes were not significant in the test group. There was a significant difference in serum lithium between the groups at 8 and 12 weeks of follow-up. There were no significant differences in the change in serum sodium, potassium, creatinine, aldosterone, creatinine clearance, and blood pressure within the group and between the groups. A significant positive correlation was found between serum lithium and aldosterone at baseline.ConclusionsIntake of add-on sodium chloride (1 gm/day) may reduce the fluctuations in serum lithium during the maintenance phase of lithium therapy in type I bipolar disorder.Disclosure of InterestNone Declared

Lithium: Managing Cognitive Impairment and Sexual Problems

IntroductionPatients taking lithium complain of cognitive impairment. This was assumed to be real by expert clinicians for years until relatively recent objective neuropsychological studies have failed to verify much impairment.Second and perhaps underemphasized side effect from lithium is sexual dysfunction.ObjectivesThe objective of this review is to highlight for the cognitive and sexual problems, which are two very important areas for discussion with patients. It should be brought up right when beginning to prescribe.MethodsData was obtained through an internet-based literature review, using the research platform PubMed and the World Health Organization website. Eight articles from the last five years were included.ResultsDue to the lack of evidence in neuropsychological studies, what was considered to be impaired cognitive function in the past has been recently considered a loss of sharp thinking in manic states or mild persisting depressions.About sexual dysfunction it is important eliminating other possible causes, lowering lithium dose, timing sex, and taking sildenafil and 240 mg/day of aspirin may help.ConclusionsCognitive impairment and sexual problems are two important subjects that involve the issues of dosing, of managing and dealing with people’s willingness to take lithium.Providing psychoeducation about these possible effects can head off abrupt discontinuation impulses.Disclosure of InterestNone Declared

Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats.

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3β, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3β protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3β and possibly associated with a decrease in muscle injury.

Removal of lithium from aqueous solutions by solid-phase extraction using sawdust loaded with magnetite nanoparticles and study of apoptosis, MDA and 8-OHdG caused by lithium toxicity in fish brain.

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism (Carassius auratus) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.