Long-term Lithium Therapy Research Articles

Effects of long-term lithium therapy on kidney functioning in mood disorders: A population-based historical cohort study.

Lithium is Food and Drug Administration-approved for bipolar disorder (BD) and is also used in depressive disorders but is underutilized due to concerns about chronic kidney disease (CKD). We explored clinical and demographic profiles of patients on long-term lithium therapy (LTLT) and assessed kidney function. Our aims were to identify the predictors for CKD stage ≥3 and the impact of lithium discontinuation post-CKD diagnosis. We conducted a population-based historical cohort study of adult patients with mood disorders on LTLT at the Marshfield Clinical Health System from 1990 to 2019. Data on lithium therapy and kidney-related information (estimated glomerular filtration rate and CKD) were extracted from electronic medical records. Among 1603 patients with mood disorders (mean age 42.1 years, 60% females), 15.3% (n = 246) developed CKD stage ≥3. Patients without CKD were on lithium for 4.5 years, compared to 6.6 years for those with CKD. Hypertension, age, and BD were significant CKD risk factors. Kidney function declined linearly with lithium duration, returning to pre-treatment trajectory in patients without CKD but showed no improvement in those with CKD after lithium discontinuation. The findings suggest that CKD occurs in 15% of patients with mood disorder receiving LTLT, with its progression potentially influenced by existing comorbidities rather than lithium alone. These results underscore the importance of monitoring kidney function in patients on LTLT and considering individual risk factors for CKD development. In patients who developed CKD, Li discontinuation did not impact change in kidney function.

Sonochemical synthesis of graphene oxide-Ag2O nanozyme as an oxidize-like mimic for the highly sensitive detection of lithium in blood serum

Bipolar disorder is commonly treated with lithium carbonate. The concentration of lithium in the blood serum should be closely monitored in patients who require long-term lithium therapy. To date, no colorimetric method of detecting lithium ions has been reported using nanosensors. We have developed a novel chemosensor based on nanozyme (NZ) to address this clinical need. The GO-Ag2O NZs were synthesized by a sonochemical method and used as a colorimetric nanosensor to detect lithium ions in human blood serum (Li (I)). To characterize NZs, various techniques were employed, including XRD, FTIR, TEM, FESEM, EDX, Raman spectroscopy, BET, DLS, Zeta potential, and ICP-OES. According to TEM and FESEM images of GO-Ag2O, the nanoparticles (NPs) of Ag2O are uniformly distributed on the surface of 2D graphene oxide sheets. In addition, silver oxide nanoparticles exhibited a cubic morphology with an average size of 3.5 nm. We have examined the performance of the NZs in an aqueous medium and in human blood serum that contains Li (I). A colorimetric test revealed that NZs synthesized in the presence of ultrasound were more sensitive to Li (I). According to the linearity of the calibration curves’ ranges, Li (I) has a limit of detection (LOD) of 0.01 µg/mL. Furthermore, it displayed a linear range between 0 and 12 µg/mL. GO-Ag2O NZs showed noticeable color changes from green to orange after exposure to Li (I). An incubation time of two minutes was found to be the most effective for sensing. This innovative approach provides a reliable method for monitoring lithium levels and ensuring patient safety during long-term lithium therapy for bipolar disorder.

Lithium nephropathy in Bipolar Disorder: a clinical challenge

IntroductionLithium nephropathy can occur in long-term lithium-treated bipolar disorder patients. Key risk factors include duration of lithium exposure, cumulative dose, acute intoxication episodes, advanced age, and comorbidities such as hypertension, diabetes mellitus, hyperparathyroidism, and hyperuricemia, along with concurrent use of antipsychotics. The clinical presentation is gradual, with mild proteinuria, often accompanied by arginine vasopressin resistance. Histological studies show a correlation between interstitial fibrosis and cumulative lithium duration. Approximately 15 to 25 per cent of exposed patients may experience a gradual decline in glomerular filtration rate. The outcome after lithium discontinuation varies.ObjectivesThis case study aims to analyze and document the clinical presentation, diagnosis, and management of lithium nephropathy in a patient with Bipolar Disorder.MethodsWe gathered data on the medical history, lab results, and treatment approach for a patient with Bipolar Disorder.ResultsThe patient, a 50-year-old woman, had been under the care of Psychiatry since 2008 due to a diagnosis of Bipolar Disorder Type I. During this time, she had experienced depressive and manic episodes but had not presented significant symptom decompensation for the past 14 years, successfully managed with lithium at a current dose of 600 mg per day. However, on this occasion, the patient sought hospitalization due to recent behavioural disturbances, including restlessness, disinhibition, abrupt changes in behaviour, pressured speech, sleep problems, agitation, and aggression. The patient also reported an increased sense of polyuria and polydipsia. Evaluation in the emergency department revealed elevated lithium levels of 1.47 mmol/L and hypokalemia, that justified lithium withdrawal. After lithium levels decreased, an estimated glomerular filtration rate remained low. She was diagnosed with lithium nephropathy, an adverse effect of long-term lithium therapy. Treatment with lithium changed to sodium valproate. Treatment with asenapine started and sustained for two months. Over the following two years, the patient experienced four additional hospital admissions in Psychiatry due to manic episodes.Conclusions Long-term lithium therapy can lead to lithium nephropathy with symptoms such as polyuria, polydipsia, and acute kidney failure. Consistent monitoring of patients receiving lithium is crucial to detect potential adverse effects.This case highlights the challenges in managing bipolar patients, as discontinuing lithium exacerbated symptoms despite switching to sodium valproate for nephropathy prevention. Long-term lithium treatment, while effective for bipolar disorder, poses significant renal risks. We emphasize continuous renal function monitoring and assessing the risk-benefit of lithium treatment while actively researching lithium nephropathy and its impact on glomerular function.Disclosure of InterestNone Declared

Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects.

Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population

BackgroundLong-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. MethodsPatients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. ResultsA total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1–11.4), and mean parathyroid hormone was 272 pg/mL (range 108–622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. ConclusionsScreening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

The Effect of Long-Term Lithium Use on Renal Functions in Patients with Bipolar Disorder

It is known that especially glomerular side effects of lithium lead to serious consequences such as end-stage renal disease. Therefore, it is critical to evaluate patients on long-term lithium therapy for glomerular pathologies. The present study investigated the changes in renal functions, prevalence of renal failure and progress in patients have been followed up for at least six years with bipolar disorders (BD) and on regular lithium treatment. 51 patients with BD and 38 age and sex matched healthy controls were enrolled for the study. The serum blood urea nitrogen (BUN), creatinine, uric acid, electrolytes, calcium (Ca), phosphorus (P), vitamin D (25-OH D3), parathyroid hormone (PTH) and eGFR levels were measured to compare the kidney functions of patients and control group. The relation between the renal functions and mean serum lithium levels and duration of lithium treatment were also investigated. Mean eGFR level, 25-OH D3 and urine density of patients with were significantly lower whereas creatinine, uric acid, Ca and PTH were significantly higher than that of controls.. The duration of lithium treatment and mean lithium levels were negatively correlated with eGFR level. Eight of 51 patients have critical eGFR level as lover than 60ml/minute thus further nephrological investigation was needed. The study revealed that the renal functions of the patient group was significantly lower than controls. The findings suggested that both duration of lithium treatment and high serum lithium levels may have a negative impact on renal functions. These findings suggest that it is important to clarify the response type to lithium in patients who are on long term treatment with lithium and maintain the treatment with the lowest possible therapeutic serum levels and carefully monitoring the renal functions in patients with good response to lithium.

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

BackgroundLithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD).MethodsWe conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization.ResultsA total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function.ConclusionThis study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study.

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

Long-Term Lithium Therapy: Side Effects and Interactions

Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, neurological, thyroid, metabolic, cognitive, dermatological, cardiologic, and sexual are listed. Probably, the most important negative effect of lithium, occurring mostly after 10-20 years of its administration, is interstitial nephropathy. Beneficial side-effects of long-term lithium therapy also occur such as anti-suicidal, antiviral, and anti-dementia ones. Pharmacokinetic and pharmacodynamic interactions of lithium, mostly those with other drugs, may have an impact on the success of long-term lithium treatment. This paper makes the narrative updated review of lithium-induced side-effects and interactions that may influence its prophylactic effect in bipolar disorder. Their description, mechanisms, and management strategies are provided. The papers appearing in recent years focused mainly on the long-term lithium treatment are reviewed in detail, including recent research performed at Department of Psychiatry, Poznan University of Medical Sciences, Poland. Their own observations on ultra-long lithium treatment of patients with bipolar disorder are also presented. The review can help psychiatrists to perform a successful lithium prophylaxis in bipolar patients.

Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy.

Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design. Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations). Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48-67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4-6] vs 3 [IQR, 2-5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85-38.0 [log-rank P = 0.001]]. Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis.

Dietary lithium intake, graft failure and mortality in kidney transplant recipients.

Long-term high-dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies have revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival. Urinary lithium concentration was measured using inductively coupled plasma mass spectrometry in 642 stable kidney transplant recipients (KTRs). Graft failure was defined as the start of dialysis or retransplantation and kidney function decline was defined as a doubling of serum creatinine. The median urinary lithium excretion was 3.03μmol/24 h [interquartile range (IQR) 2.31-4.01]. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3years (IQR 4.5-6.0), 79 (12%) KTRs developed graft failure and 127 (20%) KTRs developed kidney function decline. Higher urinary lithium excretion was associated with a lower risk of graft failure {hazard ratio [HR] per doubling 0.54 [95% confidence interval (CI) 0.38-0.79]} and kidney function decline [HR per doubling 0.73 (95% CI 0.54-0.99)]. These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was a significant effect modification with the use of proliferation inhibitors (P=.05) and baseline estimated glomerular filtration rate (eGFR; P<.001), with higher urinary lithium excretion being more protective in KTRs not using proliferation inhibitors and in KTRs with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with a reduced risk of all-cause mortality [HR 0.64 (95% CI 0.49-0.83); P=.001]. Dietary lithium intake may be a potentially modifiable, yet rather overlooked, risk factor for adverse long-term kidney graft outcomes and patient survival. https://clinicaltrials.gov/ct2/show/NCT02811835.

Lithium increases cortical and subcortical volumes in subjects with bipolar disorder

Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients’ lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics.

P.0680 Hypernatremia secondary to kidney injury after long-term lithium therapy during COIVD-19 pandemic

P.0680 Hypernatremia secondary to kidney injury after long-term lithium therapy during COIVD-19 pandemic

Renal effects of long-term lithium therapy, revisited.

The aim of this study was to investigate the effect of lithium treatment on renal function and to determine influencing factors. In addition, the utility of spot urine protein/creatinine ratio in detection of lithium induced nephropathy was also investigated. Serum concentrations of lithium, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), and urinalysis including protein/creatinine ratio were measured in 375 patients using lithium. Patients taking lithium for ≥8 years had higher BUN, creatinine levels, percentage of proteinuria, percentages of stage 2 and 3 chronic kidney disease (CKD); lower urine density and eGFR compared to patients taking lithium <8 years. Urine density was lower in groups with >0.8 and 0.6-0.8 mmol/L lithium level than <0.6 mmol/L. Predictors of CKD were serum level of lithium, dose of lithium, cumulative duration of lithium use, age at onset of illness, and caffeine consumption. Detrimental effects of lithium on renal functions were detected after lithium use for ≥8 years. Proteinuria measured by spot urine protein/creatinine ratio can be detected even when eGFR is >90 ml/min/1.73 m2 . Spot urine protein/creatinine ratio, which is a cost-effective and practical laboratory test, can be used to monitor lithium-treated patients.

Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study.

Long-term lithium therapy (LTLT) has been associated with kidney insufficiency in bipolar disorder (BD). We aimed to investigate the risk factors of chronic kidney disease (CKD) development and progression among BD patients receiving LTLT. We included adult patients with BD on LTLT (≥1year) who were enrolled in the Mayo Clinic Bipolar Biobank, Rochester, Minnesota. We reviewed electronic medical records to extract information related to lithium therapy and kidney-related data to assess changes in the estimated glomerular filtration rate (eGFR). CKD severity was assessed based on eGFR. Among 154 patients who received LTLT, 41 patients (27%) developed CKD, of whom 20 (49%) patients continued lithium (continuers) and 19 (46%) discontinued it (discontinuers). The median time to stage 3 CKD development was 21.7years from the start of Li treatment. Type-2 diabetes mellitus and benzodiazepine use were independent predictors for CKD development in the survival analysis, after controlling for age. The subsequent CKD progression rate did not differ between continuers and discontinuers (mean GFR 48.6 vs. 44.1, p=0.13) at the end of follow-up duration (mean duration: 3.5±4.4years for continuers and 4.9±5.3years for discontinuers). CKD was observed in one fourth of patients with BD receiving LTLT. There was no significant difference in the progression of CKD among Li continuers versus discontinuers, at the mean follow-up duration of 4.2years, after the CKD diagnosis. Progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone.

A severe course of the COVID-19 in a patient receiving prophylactically lithium

Introduction. The SARS-CoV2 pandemic makes a challenge for patients with bipolar disorder receiving prophylactically lithium. There have been findings pointing to the antiviral effect of lithium which arouse suppositions that using the drug may prevent or attenuate the illness. Case report. A 58-year old male patient, inhabitant of Lombardy, with bipolar disorder for more than 20 years, who have been receiving prophylactically lithium and valproate since 2010. In February 2020, became infected with COVID-19 disease, with a temperature of 40°C; chest pain, dyspnoea, and dry cough developed. SARS-CoV2 infection was confirmed by PCR test; chest imaging showed characteristic changes for the infection. He was treated with antibiotics, oxygen, fluids, and antipyretic drugs. Hyperpyrexia and respiratory problems persisted for 40 day; full recovery occurred after 7 weeks. Comments. This case shows that also in patients on long-term lithium therapy, COVID-19 may run a severe course.

Effect of lithium carbonate on the function of the thyroid gland: mechanism of action and clinical implications.

Lithium carbonate, a drug known for more than 100 years, has been successfully used as a psychiatric medication. Currently, it is a commonly used drug to treat patients with unipolar and bipolar depression, and for the prophylaxis of bipolar disorders and acute mania. Lithium salts may cause the development of goiter, hypothyroidism, or rarely hyperthyroidism. The present review examined the current state of knowledge on the effect of lithium carbonate on the thyroid gland. The Pubmed database and Google Scholar were searched for articles related to the effects of lithium therapy on the thyroid gland function published up to February 2020. Studies that examined the mechanism of action of lithium at the molecular level, including pharmacokinetics, and focused on its effects on the thyroid gland were included. Lithium as a mood-stabilizing drug has a complex mechanism of action. Because of the active transport of Na+/I- ions, lithium, despite its concentration gradient, is accumulated in the thyroid gland at a concentration 3 - 4 times higher than that in the plasma. It can inhibit the formation of colloid in thyrocytes, change the structure of thyroglobulin, weaken the iodination of tyrosines, and disrupt their coupling. In addition, it reduces the clearance of free thyroxine in the serum, thereby indirectly reducing the activity of 5-deiodinase type 1 and 2 and reducing the deiodination of these hormones in the liver. Taken together, this review provides recommendations for monitoring the thyroid gland in patients who require long-term lithium therapy. Prior to the initiation of lithium therapy, thyroid ultrasound should be performed, and the levels of thyroid hormones (fT3 and fT4), TSH, and antithyroid peroxidase and antithyroglobulin antibodies should be measured. If the patient shows normal thyroid function, TSH level measurement and thyroid ultrasound should be performed at 6- to 12-month intervals for long term.

A Rare but Reversible Cause of Lithium-Induced Bradycardia

Lithium is a well-known medication that has been used for many years to treat mood disorders. One of its side effects is cardiotoxicity, which usually occurs at serum lithium levels > 1.5 mEq/L but rarely occurs when therapeutic levels of lithium are used. Other causes of bradycardia should be eliminated by performing a detailed workup that includes calcium level, thyroid function, and cardiac workup, with consideration of any medication interactions. Lithium-induced bradycardia is reversible upon discontinuation of lithium, but irreversible sinus node can occur and may warrant permanent insertion of a pacemaker to maintain sinus rhythm when long-term lithium therapy is required. Herein, we describe the case of a 42-year-old woman who presented with symptomatic bradycardia. Bipolar disorder was described in her past medical history, and she was receiving lithium therapy. A detailed workup indicated bradycardia secondary to lithium use. Her condition improved after discontinuation of the lithium, and normal sinus rhythm was restored over the next three days.

Methodology for rapid assessment of blood lithium levels in ultramicro volumes of blood plasma for applications in personal monitoring of patients with bipolar mood disorder.

Bipolar disorder (BD) is a common mental health condition, characterized by extreme changes in mood, energy, and behavior. BD is often managed through mood-stabilizing medications, of which lithium formulations remain the most reliable and effective at reducing the risk of suicide. To achieve adequate and consistent efficacy, lithium concentrations need to be maintained within a narrow therapeutic range (0.4 to 1.2 mmol / L). Because of its narrow therapeutic index, long-term lithium therapy is associated with serious side effects and risks of toxicity. It is believed that the availability of a personal blood lithium analyzer would benefit patients who are on lithium treatment. We detail the results of a spectrophotometric method performed on ultramicro volumes to determine blood plasma lithium concentrations as compared with reference measurements of flame photometry, and validated in samples of unknown lithium content. Applying multiple linear regression, lithium concentrations could be determined in a rapid manner using full-range spectra or triwavelength data. Both techniques highly correlated with reference standards and could predict lithium levels accurately (R2 = 0.794214 and RMSEP = 0.209584, and R2 = 0.863921 and RMSEP = 0.167524, respectively). Therefore, this method can be a useful for rapid assessment of blood lithium in nonlaboratory settings i.e., general practices, hospital clinics, and community health centers by healthcare professionals and/or by patients. Future work will now focus on completion of a miniaturized and integrated system that will deliver a portable and personal lithium-monitoring device.

Glutamate-Related Antibodies and Peripheral Insulin-Like Growth Factor in Bipolar Disorder and Lithium Prophylaxis

Aims: The aim of this study was to evaluate serum levels of the antineuronal antibodies anti-N-methyl-D-aspartate receptor (NMDAR) and anti-glutamic acid decarboxylase (GAD), and insulin-like growth factor 1 (IGF-1), in patients with bipolar disorder (BD), during manic and depressive episodes and in remission compared to euthymic patients receiving long-term lithium therapy. Methods: Serum levels of anti-NMDAR and anti-GAD 450/620 antibodies, as well as IGF-1, were measured using the ELISA method in 19 manic and 17 depressed patients both in an acute episode and in remission after the episode. All of the subjects were under pharmacological treatment. The control group included 18 euthymic BD patients receiving lithium for 9–44 years (mean 22 ± 11) in whom a single measurement was performed. Results: Serum levels of anti-NMDAR antibodies were higher in acute manic episodes than in lithium-treated patients. Serum levels of anti-GAD 450/620 antibodies were higher in acute manic and depressive episodes compared to remission after the respective episode. Their values in both acute manic and depressive episodes were higher than those in lithium-treated patients. Serum levels of IGF-1 were higher in acute manic episodes and in remission after mania than in lithium-treated patients. Conclusion: Higher levels of anti-NMDAR and anti-GAD antibodies during episodes may point to an abnormality in the glutamatergic system in BD. Increased levels of IGF-1 during an acute manic episode and in remission after mania may constitute a compensatory mechanism against excitotoxicity. Lower levels of anti-NMDAR, anti-GAD antibodies, and IGF-1 during long-term lithium treatment may reflect normalization of this processes, contributing to mood stabilization.