Serum Lithium Levels Research Articles

Lithium-induced nephropathy; One medication with multiple side effects: a case report

BackgroundLithium carbonate is commonly used in the treatment of bipolar disorder. A spectrum of side effects is associated with lithium, including nephrogenic diabetes insipidus, renal tubular acidosis, chronic tubulointerstitial nephropathy, and minimal change disease. Although the former three adverse effects are well-known, minimal change disease is relatively rare.Case presentationWe herein report a case of lithium therapy-induced minimal change disease with concurrent chronic tubulointerstitial nephropathy. A 66-year old man with bipolar disorder treated by lithium for 20 years, presented to the hospital with anasarca and decreased urine output for 4 weeks. The medical history also included hyperlipidemia, hypertension, and benign prostatic hyperplasia. Further laboratory investigation revealed elevated serum lithium (2.17 mmol/L), potassium (6.0 mmol/L), and creatinine levels (2.92 mg/dL), nephrotic range proteinuria, and hypoalbuminemia. Lithium was discontinued and the patient was treated with intravenous fluids. He underwent a kidney biopsy, which showed findings consistent with minimal change disease with concurrent acute tubular injury and chronic tubulointerstitial nephropathy. The patient was subsequently treated with steroids in an outpatient setting. He did not respond to the treatment, and hemodialysis was started.ConclusionBased on the previously reported cases and review of literature, occurrence of lithium-associated minimal change nephropathy is rare. Patients with lithium-associated minimal change disease and acute tubular injury usually respond to discontinuation of lithium therapy and/or steroid treatment. In this case, minimal change nephropathy was steroid-resistant and kidney function of the patient reported here did not recover after 6-month follow-up. We postulated the underlying cause to be minimal change disease with chronic tubulointerstitial nephropathy due to long-term lithium use. This case provides an example of a rare side effect of lithium-induced minimal change nephropathy with chronic tubulointerstitial nephropathy in addition to its well-known complication of interstitial nephritis or diabetes insipidus. In our opinion, these patients likely have much worse clinical outcome.

CAN BURNING MOUTH SYNDROME BE ASSOCIATED WITH LITHIUM DEFICIENCY? REPORT OF 2 CASES

Burning mouth syndrome (BMS) is a burning sensation or pain in an oral mucosa in which no lesion is identified. It mainly affects women over the age of 60 years, especially after menopause. Here, we report 2 cases of BMS with lithium deficiency. Both patients were female and reported a strong burning sensation on the tongue and buccal mucosa. No alteration of the oral mucosa was detected on intraoral clinical examination. There was no improvement in symptoms with therapeutic tests with antifungal and corticosteroids. Serum levels of vitamins and minerals were requested, and low serum levels of lithium and normality for other exams were observed. Lithium replacement therapy was performed with lithium carbonate once a day for 60 days. After this protocol, lithium serum levels were tested, showing satisfactory levels. After 4 months of follow-up, no symptomatology was recorded. Burning mouth syndrome (BMS) is a burning sensation or pain in an oral mucosa in which no lesion is identified. It mainly affects women over the age of 60 years, especially after menopause. Here, we report 2 cases of BMS with lithium deficiency. Both patients were female and reported a strong burning sensation on the tongue and buccal mucosa. No alteration of the oral mucosa was detected on intraoral clinical examination. There was no improvement in symptoms with therapeutic tests with antifungal and corticosteroids. Serum levels of vitamins and minerals were requested, and low serum levels of lithium and normality for other exams were observed. Lithium replacement therapy was performed with lithium carbonate once a day for 60 days. After this protocol, lithium serum levels were tested, showing satisfactory levels. After 4 months of follow-up, no symptomatology was recorded.

Lithium surveillance by community pharmacists and physicians in ambulatory patients: a retrospective cohort study

BackgroundShared care agreements between clinical pharmacists and physicians can improve suboptimal lithium monitoring in in- and outpatient settings. However, it is unknown whether incorporating community pharmacists in such agreements can also improve lithium monitoring in an outpatient setting.AimTo assess the necessity for a shared care agreement for lithium monitoring in our region by investigating: intervention rates by community pharmacists and whether those are sufficient; lithium monitoring by physicians in ambulatory patients; the extent of laboratory parameter exchange to community pharmacists.Method Patient files of lithium users were surveyed in a retrospective cohort study among 21 community pharmacies in the Northern Netherlands. Outcome was the intervention rate by community pharmacists and whether those were deemed sufficient by an expert panel. Additionally, we investigated both the percentages of patients monitored according to current guidelines and of laboratory parameters exchanged to community pharmacists.Results129 patients were included. Interventions were performed in 64.4% (n = 29), 20.8% (n = 5), and 25.0% (n = 1) of initiations, discontinuations, and dosage alterations of drugs interacting with lithium, respectively. The expert panel deemed 40.0% (n = 14) of these interventions as “insufficient”. Physicians monitored 40.3% (n = 52) of the patients according to current guidelines for lithium serum levels and kidney functions combined. Approximately half of the requested laboratory parameters were available to the community pharmacist.ConclusionIntervention rates by community pharmacists and lithium monitoring by physicians can be improved. Therefore, a shared care agreement between community pharmacists, clinical pharmacists, and physicians is needed to improve lithium monitoring in ambulatory patients.

Lithium Induced Parkinsonism: A Case Report

AimsLithium is an effective mood stabiliser for the treatment of the bipolar disorder. Its utility is not restricted to acute mania and prophylactic treatment of the bipolar disorder. Another well-known indication for its use is the treatment of refractory depression. Lithium can cause several adverse effects, and typically the side effects are dose-related. Unlike antipsychotic medications, lithium is rarely associated with drug-induced Parkinsonism.MethodsWe present a case of 78 years old gentleman who was assessed due to complaints suggestive of cognitive impairment. His past psychiatric history revealed that he was admitted to a psychiatric inpatient unit with a diagnosis of treatment-resistant depression in 1991. Lithium therapy was commenced during this admission, and he remained on lithium for 27 years. The patient was clinically stable in terms of the symptoms of depression; however, he reported bilateral postural tremors 20 years after the initiation of lithium therapy. Initially, he was diagnosed with lithium-induced tremor; however, in the following months, his symptoms had worsened, and he developed new motor disturbances, although the serum levels of lithium were within the therapeutic range. On examination, he had classic parkinsonian signs of shuffling gait, muscle rigidity in all four limbs and freezing of gait. DaT-SPECT imaging clarified the diagnosis as drug-induced Parkinsonism. As the daily lithium dosage was stopped, the patient's motor symptoms improved significantly; nevertheless, some of the symptoms persisted.ResultsThe pathophysiological mechanism behind lithium-induced Parkinsonism is unclear. The condition may develop with or without frank lithium toxicity and have diverse presentations. Literature suggests that the risk factors for lithium-induced Parkinsonism appear to be the patients' age, duration of lithium therapy, and serum lithium levels. It has been suggested that older patients have a more permeable blood-brain barrier and decreased renal clearance; hence, serum lithium levels can appear therapeutic, but brain lithium levels may be much higher. Pharmacokinetic drug-drug interactions might also contribute; thus, careful monitoring is essential.Drug-induced Parkinsonism improves with discontinuation of the offending medication; however, 10% of patients will develop a persistent and progressive parkinsonian syndrome.ConclusionThis report aims to emphasise the need to consider lithium-induced Parkinsonism when Parkinson Disease symptoms appear in chronic lithium users and close monitoring of lithium levels in geriatric populations. It is essential to recognise the condition, avoid misdiagnosis and prevent inappropriate use of anti-dopaminergic medications.

Audit of Lithium in a Psychiatry of Old Age Service

AimsThe aim of this audit is to compare our prescribing and monitoring practices in the Mental Health Service for the Elderly team (MHSE) in County Monaghan with current NICE guidelines (National Institute for Health and Care Excellence, UK). Lithium is used in the management of Bipolar Affective Disorder (BPAD) and refractory Depression in the elderly and across other patient groups. The elderly population is more vulnerable generally than other patient groups to adverse effects and toxicity from Lithium including at therapeutic doses. This is due to the increased likelihood of having other medical morbidities, interaction with other medications and the higher prevalence of renal impairment.MethodsThe audit duration was from the beginning of April to the end of June 2021. Data were collected for demographic variables and for therapeutic variables such as Lithium dose, serum Lithium level, adverse effects due to Lithium, weight and signs of Lithium toxicity. Re-audit was completed during the month of June 2021.ResultsTen patients attending the MHSE team were prescribed Lithium at the time of the audit and were included in the audit. 60% were females and 40% were males. The mean age was 77.3 years. 50% had a Depressive disorder and 50% had a diagnosis of BPAD. The mean Lithium dose was 310 mg and the mean serum Lithium level was 0.5mmol/L. All 3-monthly Lithium levels were completed. 100% were provided with information booklets, record books and BMI recorded. 60% of six-monthly Lithium levels were completed. 20% of six-monthly bloods were completed but not documented. There were eight patients prescribed Lithium in the re-audit. 62% were females and 38% were males. The mean age was 78.8 years. 75% were diagnosed with refractory Depression and 25% with BPAD. The mean Lithium dose was 337.5 mg and the mean serum Lithium level was 0.6mmol/L. 100% of patients completed their three and six-monthly serum Lithium levels and documentation was complete for 100% of patients.ConclusionWe recommend the establishment of a Lithium Clinic to ensure proper monitoring of this group. This includes clear pathways for patients to have their bloods taken (GP or hospital), pro forma reminder letters for GPs and patients, a recording table for blood results and physical variables in the patient file, alert cards and the provision of written information about Lithium for patients and carers.

Point-of-care test for rapid assessment of blood lithium levels in women with bipolar disorder during perinatal period

IntroductionDetermination of lithium levels in serum has become a standard of care due to its narrow therapeutic rang, thus an immediate test for determination of blood lithium may contribute to minimize toxicit, to avoid relapse and to ensure treatment adherence. This is particularly relevant during pregnancy and early postpartum because pharmaokinetic changes in renal physiology.ObjectivesThe aim of this study is verify Medimate point-of-care method performance and systematically compare it with the routine laboratory measurement of lithium.MethodsThis cross-sectional method comparison study was conductec in the Unit of Perinatal Mental Health in the Hospital Clinic of Barcelona. Pearson and Bland-Altman analyses were performed to assess the accuracy, precision and correlation between the capillary electrophoresis technology (Medimate MiniLab) and the ion selective electrode (ISE) potentiometry method (AVL 9180).ResultsTwenty-five women with bipolar disorder in treatment with lithium during perinatal period were enrolled, corresponding to 75 blood specimens for analyses. Correlation (r), mean difference (bias), and 95% limit of agreement (LOA) of the point-of-care method [r=0.917; bias 0.0021 (95% LOA; 0.440, 0.619) mEq/L], showed that difference between ISE method and capillary electrophoresis technology was not statistically significant.ConclusionsConsidering the practicality, the microchip capillary electrophoresis technology provides a simple and highly affordable way of measuring lithium levels in a single drop of blood outside the clinical laboratory. The Medimate point-of-care system (POC) appears well adapted for the rapid and specific detection of lithium as an alternative to the current ISE procedure.DisclosureNo significant relationships.

Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT): A Review

IntroductionLithium has a narrow therapeutic window. Frequent monitoring of both serum levels and clinical signs of toxicity is warranted because toxicity may be present even when concentrations are within the therapeutic range. Persistent neurological signs and symptoms of lithium intoxication gained clinical attention in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT).ObjectivesTo review the long-term neurological sequelae of lithium intoxication (SILENT) to highlight their clinical presentation, assessment, management and preventive measures.MethodsNon-systematic review of literature through search on PubMed/MEDLINE for publications up to 2021, following the terms syndrome of irreversible lithium-effectuated neurotoxicity.ResultsNeurological manifestations of lithium poisoning may persist, even after effective removal of the drug – SILENT. The most frequent sequelae are cerebellum and brain stem dysfunction, extrapyramidal symptoms and dementia. They may last for weeks, months or years. Infection, dehydration, deteriorating renal function or the addition of other drugs may precipitate acute toxicity. Irreversible damage is difficult to treat. Some cases show spontaneous recovery that may be total, but in others, sequelae persist. Helpful measures include the avoidance of acute intoxications with lithium, long-term and continuous dose adjustment and serum level monitoring, stricter exclusion criteria for starting lithium, and aggressive treatment of acute neurotoxicity. Once the long-term neurologic sequelae have set in, the patient should be managed according to the impediment (physical rehabilitation, speech, cognitive training).ConclusionsIt is important to raise the awareness of SILENT so that clinicians are able to avoid it. There should be a low threshold for suspecting the existence of toxicity.DisclosureNo significant relationships.

MO502: Use of Lithium, Valproate and the Risk of Acute or Chronic Kidney Disease: An Observational Study From Routine Care Data

Abstract BACKGROUND AND AIMS Lithium is an established treatment for bipolar disorder and treatment-resistant depression. Despite awareness of potential kidney damage, there is a lack of research evidence to inform on the existence and magnitude of the risk. Observational studies to date show conflicting findings, possibly explained by inadequate control populations, prevalent user bias and a lack of information on kidney function or serum lithium levels. METHOD We conducted a cohort study to compare kidney outcomes in adults who started lithium or valproate therapy in Stockholm, Sweden, during 2007–18. Within lithium users, we also compared outcomes by average serum lithium concentrations during the first year of therapy. Kidney outcomes were CKD progression (composite of >30% eGFR decline and kidney failure) and AKI (by diagnosis or KDIGO transient creatinine elevations). Propensity score weighted Cox regression was used to estimate hazard ratios with [95% confidence intervals (95% CI)] and balance 46 identified confounders. Complete collection of repeated dispensations at Swedish pharmacies allowed modelling of the time-dependent risk associated with cumulative lithium exposure. Sensitivity analyses included restricting to patients with a diagnosis of bipolar disorder, apply a 1-year lag, use of alternative weighting methods and evaluation of eGFR monitoring rates to ascertain surveillance bias between groups. RESULTS We included 16 645 individuals, of whom 5308 initiated lithium and 5638 valproate therapy. Their median age was 45 years (57% women) and median eGFR was 99 mL/min/1.73 m2. A total of 179 CKD progression events and 234 AKI were identified during a median of follow-up of 4.3 and 4.2 years, respectively. After propensity score weighting, the adjusted hazard ratio for the risk of CKD progression was 1.12 (95% CI 0.86–1.47) and for AKI 0.88 (95% CI 0.7–1.09). There was a weak, non-statistically significant association between cumulative exposure to lithium and the risk of CKD progression that was not observed for cumulative use of valproate. Results were consistent among patients with a bipolar disorder diagnosis and robust to 1-year lag or alternative weighing methods. A total of 3913 lithium users were on therapy for at least one year and underwent routine serum lithium monitoring. Compared with patients with average serum lithium levels <1.0 mEq/L, those with serum lithium ≥1.0 mEq/L (n = 270) were at a higher risk of both CKD progression (HR: 2.18; 1.28–3.71) and AKI (HR: 1.37; 0.81–2.34). CONCLUSION In this analysis of patients from routine clinical practice, the risk of kidney outcomes associated with lithium therapy did not differ from that of valproate. Modest risk magnitudes need to be offset with the effectiveness and anti-suicidal benefits of lithium. However, elevated serum lithium levels strongly predicting kidney risk, emphasizing the need for close monitoring and lithium dose-adjustment.

Association between serum lithium level and incidence of COVID-19 infection.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with 'therapeutic' (0.50-1.00) versus 'subtherapeutic' (0.05-0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69-0.97, P = 0.017) and among patients with 'therapeutic' lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67-0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Management of lithium intoxication

SUMMARYLithium is a gold standard maintenance treatment in bipolar affective disorder. It has a narrow therapeutic range, and at higher serum lithium levels there is a risk of adverse effects and toxicity. There are three patterns of lithium intoxication: acute, acute-on-chronic and chronic. We describe risk factors for lithium intoxication, mechanisms of toxicity and clinical symptoms seen in lithium intoxication. We describe both the acute and chronic effects of lithium toxicity. Lithium intoxication may be life-threatening and associated with longer-term sequelae. The management of lithium intoxication involves determining the type of intoxication. We discuss treatment strategies aimed at reducing absorption and increasing elimination of lithium. We discuss clinical indications for extracorporeal methods such as dialysis, which are used to limit the time and degree of exposure of the central nervous system to toxic lithium concentrations. Haemodialysis is the most rapid method of eliminating lithium from the body, but careful monitoring is required. Preventive strategies to mitigate the risk for lithium intoxication are discussed.

Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder: A dose-response meta-analysis

The optimal serum lithium levels for preventing the recurrence of mood episodes in bipolar disorder are controversial, especially when polarity is considered. The present study aimed to comprehensively examine the dose-response relationship between lithium concentration and risk of recurrence of mood episodes. We conducted a systematic search of major databases before January 2021 (PROSPERO: CRD42021235812). A one-stage, random-effects, restricted cubic splines model was used to estimate the dose-response relationship between lithium concentration and risk of recurrence of any or specific mood episodes (depression or mania). The effect size is shown as odds ratio (OR). Our meta-analysis included six randomised controlled trials with a total of 975 participants. The dose-response curve showed that increased serum concentrations were associated with a gradual decrease in the risk of any mood episodes (OR 0.50 at 0.60 mmol/l, OR 0.15 at 1.20 mmol/l). The risk of depression decreased slightly with a concentration of 0.60 mmol/l (OR 0.83) but dropped rapidly as the concentration increased to 1.20 mmol/l (OR 0.39). By contrast, the risk for mania initially decreased steadily (OR 0.44), but decreased only marginally (OR 0.30) as the concentration increased. To reduce the recurrence risk to 56%, prevention of depression required a higher concentration than that required for mania (1.13 mmol/l vs. 0.60 mmol/l). Our results suggest a negative dose-response relationship between serum lithium levels and risk of recurrence. In particular, the different preventive effects of serum concentration on depression and mania will be an important clinical reference.

Relationship Between Lithium Dose, Serum Concentration and Duration of Lithium Therapy with Cutaneous Side-effects in Bipolar Affective Disorder Patients

Introduction: Lithium has been used in the treatment of mood disorders for more than five decades. Despite a few studies focusing on the relationship between the dose of lithium, serum lithium levels, duration of therapy, and cutaneous side-effects, results remain inconclusive. Lithium is known to cause multiple cutaneous side-effects like acneiform eruptions, psoriasiform eruption, seborrheic dermatitis, and follicular keratitis. Aim: To evaluate the relationship between cutaneous side-effects of lithium with the serum lithium levels, dosage and duration of lithium therapy in bipolar affective disorder patients. Materials and Methods: An ambispective observational study conducted among 52 bipolar affective disorder patients on lithium therapy recruited by convenient sampling methods from both Inpatients and Outpatient Psychiatry Units of PSG Institute of medical sciences and research, Coimbatore, Tamil Nadu, India, June 2014 to August 2014. The patients with bipolar affective disorder who are either newly started on lithium or already on lithium therapy were included in the study. They were followedup to assess the effect of lithium dosage, duration of lithium and serum lithium level with skin lesions, once a month for six months and once in two months for one year. Kaplan-Meier survival analysis was done with varying lithium dosages and serum lithium levels. Association between the lithium dose and serum lithium levels with the cutaneous side-effects were calculated using the survival analysis with the p-value of <0.01. Results: Out of the total, 59.6 % of the participants were in the age group less than 40 years and 34.6 % were in the age group 40-60 years. There was almost equal distribution of males and females, 51.9% and 48.1%, respectively. Overall, 38.46% participants had cutaneous lesions. Various lithium dosage and serum lithium levels did not correlate statistically with skin reactions upto one year. Survival analysis at the end of 10 years revealed that participants with higher dosage and serum levels had higher prevalence of skin lesions (40% vs 4%: 47.1% vs 6.6% respectively, p-value <0.001). The cumulative proportion of skin lesions at the end of three, five, seven and 10 years for higher dose (>800 mg/day) was 38%, 46.9%, 52.2%, 59% and for higher lithium levels (>0.8 mEq/L) was 41%, 58.2%, 65.2%, 73.9%. Conclusion: The patients who were treated with lower dosage and who had lower serum lithium level had reduced risk for cutaneous lesions. Lithium continued to exert its mood stabilisation property even when the serum level was maintained less than 0.8 mEq/L. This resulted in better compliance

Abstract- Poster

Background:In spite of prevalent use of lithium therapy in clinical settings, there is not much published literature on lithium levels in Indian patient samplesAim:The study aimed to describe the pattern and trend of serum lithium level in consecutive serum lithium estimations between January 2015 and December 2019. It did not include 2020-2021 due to frequent COVID-19 related service disruptions in this period.Methods:This was a retrospective review of lithium laboratory records for consecutive samples received over a five year period at Department of Psychiatry, AIIMS, New Delhi.Results:A total of 4,376 samples were received over five year period (mean age: 34.98±13.06 years; 62% males; out-patient: 87.4%). One-third (36.3%) samples had serum lithium levels <0.60 mEq/L and a small percentage (3.6%) were in toxic range. Further analysis was restricted to out-patient samples within therapeutic range (0.6-1.2 mEq/L) (N=2,278). One-way between-groups ANOVA (Feb-April, May-July, Aug-Oct, Nov-Jan) was significant (F=3.021; df=3; p=0.029), with LSD post-hoc showing a small but statistically significant difference in mean lithium levels of Aug-Oct compared to Nov-Jan (p=0.007) and Feb-April (p=0.015). Further, serum lithium level was positively correlated to age (p=0.019), serum potassium (p=0.002), and inversely correlated to serum sodium (p<0.001).Conclusion:Those with older age and lower sodium levels appear to have higher lithium levels, concordant with existing literature. Serum lithium levels showed a slight but significant elevation in Aug-Oct compared to Nov-Jan and Feb-April. This finding can be explored further with respect to weather variables including temperature and humidity for same period.

Lithium-induced bilateral flapping tremors (asterixis) in geriatric mania

Asterixis (flapping tremors) is a movement disorder due to cortical or subcortical pathology that usually indicates serious underlying disease processes such as encephalopathy secondary to severe hepatic dysfunction, metabolic derangements, toxic agents, or serious adverse drug events. Mood stabilizers such as valproate and carbamazepine with or without concomitant administration of antipsychotics such as clozapine and risperidone have been implicated to induce asterixis. Lithium, a first-line mood stabilizer drug for geriatric mania, with its unique profile of side-effects due to narrow therapeutic window, is very rarely implicated to induce asterixis, especially when used as a monotherapy. We report a case of lithium-induced asterixis, ataxia, acute cognitive impairment, and altered sensorium in an elderly male with first-episode of mania, both during toxic and therapeutic serum levels of lithium. This case highlights the association between asterixis, ataxia, delirium, and lithium, substantiating the dictum “start low and go slow” in geriatric psychopharmacology.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Abstract- Poster

Lithium remains the mainstay for treatment of acute and maintenance therapy of mania in bipolar disorder. The effectiveness of lithium should be weighed against its side effect profile. The cutaneous effects of lithium may occur at normal therapeutic serum lithium levels. Types of skin reactions associated with lithium include acne conglobata, hidradenitis suppurativa, folliculitis, alopecia, thinning of hair, macular/maculopapular rashes, and diffuse, erythematous, pruritic, maculopapular eruption.A 28 year old female patient, was admitted in our hospital with symptoms of irritability, decreased sleep, talking excessively, overfamiliarity, increased energy levels, increased sexual desire. Total duration of illness being 2 months. No past treatment history. Mental status examination shows overfamiliarity, overdressed, increased psychomotor activity, pressurized speech, flight of ideas and increased self esteem. She was diagnosed as first episode mania and was given tablet sodium valproate 1500 mg and tablet olanzapine 10mg in divided doses. Later lithium 300mg was added. 4 days after starting lithium patient developed maculopapular rash over both forearms, ventral aspect and nape of neck. There were no complaints of itching or any signs of systemic infection. Rash subsided completely within 5 days after stopping lithium.Clinicians should monitor cutaneous symptoms during lithium treatment, as lithium is associated cutaneous side effects, these may result in suboptimal adherence by the patients.

Can we check serum lithium levels less often without compromising patient safety?

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder. This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases. We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40-0.79 mmol/L; 0.80-0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history. For tests within the recommended range (0.40-0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40-0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80-0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4-0.79 mmol/L group (2%), irrespective of testing frequency. We propose that for those who achieve 12 months of lithium tests within the 0.40-0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80-0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

When numbers can be misleading: lithium induced irreversible neurotoxicity at therapeutic drug levels

Objective: Lithium is a principal drug used in the treatment of bipolar disorder (BPD). Due to its narrow therapeutic index, serum levels need to be monitored regularly. In elderly patients with renal dysfunction lithium toxicity can develop paradoxically within the therapeutic range. This can lead to erroneous diagnosis and delayed treatment resulting in irreversible neurological sequelae as is described in our case. Case Presentation: A 65-year-old hypertensive female, with a 7-year history of BPD presented with decreased oral intake since 5-7 days, followed by altered sensorium. Neurological examination revealed coarse tremors in bilateral upper and lower limbs with spasticity, hyperreflexia, bilateral knee clonus. Twenty-five days earlier, she was prescribed Lithium carbonate. On evaluation she was found to have chronic kidney disease. Serum lithium levels came out to be 1.18 mg/dL (borderline high). After ruling out other differentials, a diagnosis of lithium toxicity was considered and she underwent two sessions of hemodialysis (HD) leading to significant improvement in sensorium; however, the patient had persistent dysarthria, difficulty in walking and proximal myopathy predominantly in the lower limbs. Nerve conduction studies confirmed the presence of axonal neuropathy. These findings of peripheral neuropathy (both sensory and motor) were suggestive of SILENT (syndrome of irreversible lithium-effectuated neurotoxicity). Conclusion: Unintended lithium toxicity can occur even at therapeutic levels especially in the elderlies owing to its narrow therapeutic window, complex pharmacokinetics and numerous drug interactions. Lithium can result in irreversible neurotoxicity including SILENT; therefore, a high level of suspicion is required to prevent such permanent disability.

Low‐dose lithium treatment of behavioral complications in Alzheimer’s disease: Lit‐AD randomized clinical trial

AbstractBackgroundTo evaluate low‐dose lithium treatment of agitation in Alzheimer’s disease (AD).MethodIn a four‐site trial, patients with AD and agitation/aggression on the Neuropsychiatric Inventory (NPI) were randomized, double‐blind, to lithium carbonate 150‐600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response defined by 30% reduction in NPI combined score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved. Somatic, cognitive, metabolic, and neurological side effects were assessed.ResultFifty‐eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium did not differ from placebo in agitation/aggression change scores. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p=0.26). Moderate or marked improvement on global CGI change, which incorporated behavior, cognition, and function, was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher’s exact test p&lt;0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p’s&lt;0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI, 1.18 to 8.94, p=0.01). Oral dose and serum lithium levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on any safety outcome.ConclusionLow dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted with precision pharmacological targeting of likely lithium‐responsive behavioral symptoms that overlap with mania.