Dose Of Lithium Research Articles

Correlation of the DRD2 gene polymorphism with psychopathology and predictive antimanic responses in patients with bipolar mania

To explore the correlation of the DRD2 gene polymorphism with psychopathology and predict responses in patients with mania treated with lithium and olanzapine. Sixty patients with bipolar mania were treated with lithium combined with olanzapine for 8 weeks and assessed using YMRS, HAMD, and HAMA. The DRD2 gene polymorphism rs1800497 was tested. Eleven (24.4%) manic patients achieved an early effective response according to the reduction of the YMRS score of >20% in the 2nd week, with a lower HAMA score than the no early effective response group. Twenty-three (51.1%) manic patients achieved remission according to the reduction of the YMRS score of >75% at the 8th week with a higher dose of lithium at the 8th weekend (g/day) than in the no-remission group. Manic patients with genotype GG had lower YMRS scores and lower doses and serum concentrations of olanzapine than patients with genotype AA + AG from the 4th week to the 8th week. Manic patients with genotype GG had a higher relative change in the YMRS score than those with genotype AA + AG from the 2nd week to the 8th week. No differences in HAMA or HAMD were found between the groups with genotype GG and AA + AG. There were more patients who achieved an early effective response in the 2nd week and remission in the 8th in those with genotype GG compared to those with genotype AA + AG. Manic patients with genotype GG had a greater improvement in the YMRS score due to a greater early effective response and remission, which was not related to higher doses and serum concentrations of olanzapine and lithium.

A comparison of demographic profiles, clinical profile, course, and outcome of Bipolar I Disorder and Bipolar II Disorder: Findings from the Bipolar Disorder Course and Outcome study from India (BiD-CoIN study)

Background: There is lack of data on bipolar disorder (BD) type II from India. Aim: To compare the demographic and clinical characteristics of patients with BD-I and BD-II using the data of the Bipolar Disorder Course and Outcome study from India (BiD-CoIN study). Methodology: Using the data of the BiD-CoIN study, patients with BD-I and BD-II were compared for demographic and clinical variables. Results: Out of the 773 patients, 59 (7.63%) participants had BD-II. Compared to BD-I, patients with BD-II had a higher income; were more often unemployed or housewives; had a higher mean number of episodes per year of illness, higher severity of depressive episodes, higher depressive affective morbidity, and a higher number of hypomanic episodes (in the lifetime, and number of episodes per year of illness); received lower doses of lithium and a lower number of medications; and had lower prevalence of alcohol dependence, higher prevalence of seasonality, a high proportion of them sought faith healing treatment, and a higher proportion of them have predominant depressive polarity. Conclusions: Patients with BD-I and BD-II differ from each other on certain demographic and clinical variables. The difference in the clinical variables suggests that the patients with BD-II may require different treatment approaches for management.

A Combination of Low Doses of Lithium and Valproate Improves Cognitive Outcomes after Mild Traumatic Brain Injury.

The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + VPA) for 3 weeks after a moderate-to-severe controlled cortical impact injury reduced cortical tissue loss and improved motor function. Since both lithium and valproate can exhibit toxicity at high doses, it would be beneficial to determine if this combination treatment is effective when administered at low doses and for a shorter duration, and if it can improve cognitive function, after a mild diffuse TBI. In the present study, we tested if the combination of low doses of lithium (1 mEq/kg or 0.5 mEq/kg) plus valproate (20 mg/kg) administered for 3 days after a mild fluid percussion injury can improve hippocampal-dependent learning and memory. Our data show that the combination of low-dose Li + VPA improved spatial learning and memory, effects not seen when either drug was administered alone. In addition, postinjury Li + VPA treatment improved recognition memory and sociability and reduced fear generalization. Postinjury Li + VPA also reduced the number of anti-ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia counted using a convolutional neural network, indicating a reduction in neuroinflammation. These findings indicate that low-dose Li + VPA administered acutely after mTBI may have translational utility to reduce pathology and improve cognitive function.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

Audit of Lithium Monitoring in a Mental Health for Older Persons (Dublin North City Central) Service

Abstract Background Lithium is a psychotropic medication used for the treatment of bipolar affective disorder and augmentation for treatment resistant depression. Lithium monitoring is essential due to the narrow therapeutic range of serum lithium and the potential for toxicity. Other medications with similar risk profiles, such as warfarin, have established monitoring programmes. Older adults receiving lithium therapy are at an increased risk of adverse events, given the prevalence of medical co-morbidities and changing pharmacokinetics. The authors of this audit identified the lack of formalized lithium monitoring programme in the Mental Health Service for Older Persons (MHSOP). The aim of this audit to compare monitoring practices in the MHSOP against the current gold standard Irish Medication Safety Network (IMSN) for Prescribing and Monitoring of Lithium Therapy. Methods A survey of all community medical charts identifying patients attending the service receiving lithium therapy was completed. Data collected pertained to diagnosis, treating consultant, lithium dose, if the patient received educational material, compliance with ECG and blood monitoring. Results The MHSOP active case load was 682 patients, 14 patients were prescribed lithium therapy. Cycle 1 of the audit demonstrated poor compliance of lithium monitoring against the gold standard. A lithium pack was inserted in patient files to prompt all clinicians to follow the recommended standardized monitoring of lithium therapy as per the IMSN guidelines. In cycle 2 of the audit there was an improvement in recording blood monitoring across the patient group. Conclusion The audit demonstrated improvement in compliance with international guidelines following the intervention. It was recommended that a formalized Lithium Clinic was a needed resource for the MHSOP. The lithium monitoring pack will continue to be added to clinical files, included in Non-Hospital Consultant (NCHD) induction and multi - disciplinary teaching sessions. It is proposed that the audit be repeated in one year to longitudinally assess compliance.

Improved Automated Radiosynthesis of [18F]Dolutegravir: Toward Clinical Applications.

Positron emission tomography imaging using radiolabeled dolutegravir (DTG) is an interesting approach to understand the biodistribution of this antiretroviral drug at HIV-1 sanctuary sites. In the course of clinical translation, we depict herein an improved and pharmaceutically compliant radiosynthesis of [18F]DTG from an original tin precursor. The radiosynthesis was achieved in two steps by copper-mediated radiofluorination, followed by enol ether deprotection using a kit-based AllInOne module. Ready-to-inject [18F]DTG was obtained in 20 ± 5% (n = 12) decay-corrected radiochemical yield within 90 min, representing a 4-fold increase compared to the previously published three-step radiosynthesis. Quality control was carried out with three consecutive [18F]DTG productions according to the current European Pharmacopoeia guidelines, which include pH determination, identity and purity (chemical, radiochemical, and radionuclide) assessments, residual solvent quantification, dosage of lithium, copper, and tin traces, sterility and bacterial endotoxin tests. [18F]DTG (∼2 GBq) was obtained with a molar activity of 59 ± 2 GBq/μmol at the time of injection and was suitable for human applications.

Peripartum lithium management: Early maternal and neonatal outcomes

BackgroundIt has been suggested that a 30–50 % lithium dose reduction or lithium discontinuation 24-48 h before delivery could minimize neonatal complications. We investigated the maternal lithemia changes around delivery after a brief discontinuation, the placental transfer of lithium at delivery, and the association between neonatal lithemia at delivery and acute neonatal outcomes. MethodsA retrospective observational cohort study was conducted in a teaching hospital (November/2006-December/2018). Data was extracted from the medical records. We included psychopathologically stable women, with a singleton pregnancy, treated with lithium in late pregnancy, with at least one maternal and neonatal lithemia at delivery. Lithium was discontinued 12 h before a scheduled caesarean section or induction, or at admission day to hospital birth; and restarted 6-12 h post. ResultsSixty-six mother-infant pairs were included, and 226 maternal and 66 neonatal lithemias were obtained. We found slight maternal lithemia fluctuations close to 0.20 mEq/L, and early postpartum relapse of 6 %. The mean (SD) umbilical cord/mother intrapartum lithemia ratio was 1.10 (0.17). Fifty-six percent of neonates presented transient acute complications. Neonatal hypotonia was the most frequent outcome (N = 15). Mean lithemia were 0.178 mEq/L higher in those with hypotonia than in those without (p = 0.028). LimitationsIt is a retrospective cohort of a moderate sample size of healthy uncomplicated pregnancies and results cannot be generalized to all pregnant treated with lithium. ConclusionsLithium transfers completely across the placenta. A brief predelivery lithium discontinuation was associated with slight maternal lithemia fluctuations. Neonates exposed intrautero to lithium present frequent but transient acute effects.

Retrospective Review of Postpartum Lithium Use Including During Lactation.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Lithium Ions as Modulators of Complex Biological Processes: The Conundrum of Multiple Targets, Responsiveness and Non-Responsiveness, and the Potential to Prevent or Correct Dysregulation of Systems during Aging and in Disease.

Lithium is one of the lightest elements on Earth and it has been in the environment since the formation of the galaxy. While a common element, it has not been found to be an essential element in biological processes, ranging from single cell organisms to Homo sapiens. Instead, at an early stage of evolution, organisms committed to a range of elements such as sodium, potassium, calcium, magnesium, zinc, and iron to serve essential functions. Such ions serve critical functions in ion channels, as co-factors in enzymes, as a cofactor in oxygen transport, in DNA replication, as a storage molecule in bone and liver, and in a variety of other roles in biological processes. While seemingly excluded from a major essential role in such processes, lithium ions appear to be able to modulate a variety of biological processes and "correct" deviation from normal activity, as a deficiency of lithium can have biological consequences. Lithium salts are found in low levels in many foods and water supplies, but the effectiveness of Li salts to affect biological systems came to recent prominence with the work of Cade, who reported that administrating Li salts calmed guinea pigs and was subsequently effective at relatively high doses to "normalize" a subset of patients with bipolar disorders. Because of its ability to modulate many biological pathways and processes (e.g., cyclic AMP, GSK-3beta, inositol metabolism, NaK ATPases, neuro processes and centers, immune-related events, respectively) both in vitro and in vivo and during development and adult life, Li salts have become both a useful tool to better understand the molecular regulation of such processes and to also provide insights into altered biological processes in vivo during aging and in disease states. While the range of targets for lithium action supports its possible role as a modulator of biological dysregulation, it presents a conundrum for researchers attempting to elucidate its specific primary target in different tissues in vivo. This review will discuss aspects of the state of knowledge regarding some of the systems that can be influenced, focusing on those involving neural and autoimmunity as examples, some of the mechanisms involved, examples of how Li salts can be used to study model systems, as well as suggesting areas where the use of Li salts could lead to additional insights into both disease mechanisms and natural processes at the molecular and cell levels. In addition, caveats regarding lithium doses used, the strengths and weaknesses of rodent models, the background genetics of the strain of mice or rats employed, and the sex of the animals or the cells used, are discussed. Low-dose lithium may have excellent potential, alone or in combination with other interventions to prevent or alleviate aging-associated conditions and disease progression.

Impact of single versus multiple dose lithium on renal dysfunction in bipolar patients: A retrospective cohort study

AbstractAimBipolar disorder significantly affects social functioning and maintenance treatment is crucial. Lithium is considered as a first‐line maintenance treatment in all treatment guidelines, but careful administration is necessary due to concerns about renal dysfunction caused by its use. Lithium can be administered in divided doses from two to three times a day or once a day. However, it is controversial which regimen, single or multiple dose, should be recommended in light of adverse effects. This study aims to clarify the difference in renal dysfunction due to the number of divided lithium doses using data from the electronic medical record in a retrospective cohort.MethodsWe targeted 72 patients who were prescribed lithium carbonate for bipolar disorder in the Juntendo University Hospital electronic medical record from April 2021 to March 2023. There were 35 cases in the single‐dose group and 37 cases in the multiple‐dose group. The outcome was the change in creatinine and estimated glomerular filtration rate (eGFR) during the observation period. The effect of the regimen was evaluated using multiple regression analysis.ResultsThere were no significant differences in the change in creatinine and eGFR between the single‐ and the multiple‐dose group, though renal function measured by creatinine and eGFR significantly worsened depending on the duration of treatment or aging.ConclusionThere was no significant difference in renal dysfunction between the single‐dose group and the multiple‐dose group; thus, considering the expected positive effect on adherence, a once‐daily regimen is recommended in maintenance lithium treatment.

Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants

BackgroundLithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (7Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose. MethodsLithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2–7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional 7Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout. Results7Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher 7Li-signal intensities (approximately 2–4×) compared to other study participants. LimitationsLithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of 7Li exhibits imperfect spatial separation of signal from adjacent pixels. Conclusions7Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10–60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

Impact of Lithium on the Immune System: An Investigation of T-Cell Subpopulations and Cytokine Responses in Rats.

The aim of this study was to investigate the dose-dependent adverse effects of long-term dietary lithium administration on specific aspects of the defense system in rats. Additionally, the study aimed to explore the inflammatory activities of lithium beyond its recognized anti-inflammatory properties. Forty Wistar Albino rats were involved, which were randomly allocated into the control and four treatment groups. The control group received standard rat feed, and the experimental groups' diet was added 1g/kg, 1.4g/kg, 1.8g/kg, and 2.2g/kg lithium bicarbonate, respectively. CD4+, CD8+, and CD161 + cells were assessed by flow cytometry. TNF-α, IFN-γ, IL-1β, and IL-2 and IL-4, IL-6, and IL-10 levels were measured. The proportion of CD4 + cells and the CD4+/CD8 + ratio (P = 0.005 and P = 0.038, respectively) were reduced with the highest dose of lithium compared to the control group. The data regarding pro-inflammatory cytokines showed a dose-dependent increase in serum TNF-α and IFN-γ levels (P = 0.023 and P = 0.001, respectively). On the other hand, serum IL-1β and IL-2 levels were decreased in a dose-dependent manner (P = 0. 001 and P = 0. 001, respectively). As for anti-inflammatory cytokines, a dose-dependent decrease was determined in serum IL-4 level (P = 0.002), while no significant changes were noted in IL-6 and IL-10 levels (P = 0.507 and P = 0.732, respectively). In conclusion, lithium adversely impacted the cellular defense system. Furthermore, apart from its anti-inflammatory properties, lithium exhibited cytokine-mediated inflammatory activities. Therefore, lithium's potential adverse effects on the immune system should be considered in immunodeficient patients and those with an inflammatory status treated with high doses of lithium.

A Therapeutic Dose of Lithium Triggers Anti-inflammatory Mechanisms in The Kidneys of Treated Mice

Lithium (Li+) is an effective mood stabilizer in people with schizoaffective disorders with more than 2 million prescriptions per year. Accumulation of Li+ in blood can cause neprotoxicity, manifesting in nephrogenic diabetes insipidus, renal tubular acidosis and tubulointerstitial nephropathy. Damage to renal cells often leads to a local immune response, playing a pivotal role in the ensuing renal injury and subsequent recovery. While both pro- and anti-inflammatory actions of Li+ were reported in various tissues, our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6 mice receiving a 0.3% lithium carbonate diet for 28 days. Given the insidious development of Li+-induced renal injury, we hypothesize that nephrotoxic effects of Li+ are alleviated by its anti-inflammatory action. We used fluorescence-activated cell sorting, qPCR, immunoblotting and proteome profiler arrays to assess the pyroptotic inflammatory cascade, characterize the infiltrating immune cells and cytokine markers in the renal tissue isolated from Li+-treated and control mice. We found that both biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinase-associated lipocalin, NGAL, are elevated in the renal tissue of Li+-treated mice. This correlated with a moderate but significant increase in renal fibrosis in mice on Li+ diet. Expression of most genes associated with pyroptotic inflammatory cascade, including NLRP3, Casp-1, IL-1b, was not different in the renal tissue isolated from control and Li+-treated mice. Higher mRNA levels of apoptosis-associated speck-like protein (ASC), in the renal tissue of Li+-treated mice could be attributed to its a pro-apoptotic, rather than inflammasome forming, function. This is in line with elevated levels of CD93 marker in the kidneys of mice on Li+ diet, reflecting increased clearance of apoptotic cells. In general, Li+-treated mice had markedly higher levels of anti-inflammatory cytokine markers in the renal tissue, most notably, IL-10 and adiponectin, and lower abundance of pro-inflammatory markers, such as CD26, CLCX16, PCSK9 and osteopontin. Higher abundance of proinflammatory IL-6 in the kidneys of Li+-treated mice made a notable exception. However, this cytokine can also be released by tubular epithelial cells under insult and induce polarization of anti-inflammatory M2 macrophages. Mice on Li+-diet had higher levels of macrophages (F4.80+ cells) in the renal tissue. Future studies will determine their polarization phenotype. Overall, our results suggest that Li+-induced toxic insult to the tubular epithelial cells is paralleled by the anti-inflammatory immune response localized to the renal tissue. NIDDK 1R01DK125464. This is the full abstract presented at the American Physiology Summit 2024 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.

An open label pilot trial of low-dose lithium for young people at ultra-high risk for psychosis.

Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side-effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side-effect assessment indicated that lithium was well-tolerated. 64% (n = 16) of participants in the lithium group were lithium-adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. With a side-effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort.

Concomitant lithium increases radioiodine uptake and absorbed doses per administered activity in graves' disease: comparison of conventional versus lithium-augmented radioiodine therapy.

BackgroundLithium inhibits iodine and thyroid hormone release from thyroid cells, possibly increasing radioiodine retention and anti-hyperthyroid efficacy when given adjunctively to radioiodine therapy (RAI) of Graves’ disease (GD). However, the literature contains limited dosimetric data regarding the influence of concomitant lithium in this setting.MethodsWe retrospectively compared dosimetric variables in patients undergoing RAI with/without adjunctive lithium (n = 52 each). We assessed two low-dose, short-duration oral lithium carbonate regimens, 450 mg/d (n = 22) or 900 mg/d (n = 30), for a mean of 4.7 ± 1.4 d starting upon RAI administration. Patients underwent diagnostic testing to measure thyroidal radioiodine uptake (RAIU) 24 h ± 2 h after ingesting up to 5 MBq radioiodine, receiving individualized RAI activities 24 h later. Using ≥3 RAIU daily measurements starting 24 h post-RAI, researchers were able to determine the effective radioiodine half-life and absorbed dose to the thyroid; we also calculated the absorbed dose per administered activity concentration within that organ. Rates of GD cure, defined as reaching euthyroidism or hypothyroidism post-RAI, were evaluated in patients with ~6 months or longer post-RAI follow-up.ResultsThe lithium dosage subgroups had similar dosimetric values and thus are considered together. Lithium patients and controls had similar average “diagnostic” RAIU (51.1% ± 15.7% vs. 50.6% ± 13.8%, p = 0.820), but the former had significantly higher RAIU post-RAI (56.3% ± 13.5% vs. 49.1% ± 13.5%, p = 0.002), reflecting significantly greater change in the former (+16.2% ± 30.4% vs. -1.8% ± 16.1%, p = 0.001). Radioiodine effective half-life was non-significantly longer in lithium patients (5.43 ± 1.50 d vs. 5.08 ± 1.16 d, p = 0.192). The mean RAI administered activity was 27% less in lithium patients (677 ± 294 MBq vs. 930 ± 433 MBq, p = 0.001), but GD cure rates were similar (83% [39/47] vs. 82% [33/40], p = 0.954), possibly due to the significantly higher thyroid dose in the lithium patients, especially in thyroid gland with a volume ≤ 20 mL (1.04 ± 0.44 Gy/MBq vs. 0.76 ± 0.30 Gy/MBq, p = 0.020). Day 3 serum lithium concentrations were low (450 mg/d: 0.26 ± 0.12 mmol/L, 900 mg/d: 0.50 ± 0.18 mmol/L); no lithium toxicity was noted.ConclusionLithium augmentation may increase the RAIU and thyroid absorbed dose, permitting potentially decreased RAI activities without sacrificing efficacy. Our observations should be confirmed in a prospective, randomized trial.

Late Onset Bipolar Disorder (LOBD): a case report

Introduction Bipolar disorder (BD) in the elderly patient may present as the evolution of illness initiated earlier in life or as a new-onset entity. Therefore, two groups of patients are distinguished: “late onset” (LOBD) when the first mania occurs in old age and “early onset” in elderly patients with long-standing history. BD in elderly patients (≥60 years) constitutes 25% of all BD cases. Specific aspects of older age bipolar disorder (OABD) are somatic and psychiatric comorbidity, impaired cognition and age-related psychosocial functioning. The management of BD in the elderly is complex given the high sensitivity of these patients to pharmacological side effects, particularly of psychotropic drugs.ObjectivesThe case of a patient with LOBD is presented, followed by a theoretical review of the subject.MethodsA case is presented with a bibliographic review.Results A 76-year-old woman who had no prior history of mental health issues until March 2023 when she was initially admitted to a geriatric hospitalization unit for manifesting manic symptoms. She was readmitted in July 2023 due to worsening depressive symptoms that included a declining mood, passive thoughts of death, deterioration in self-care, weight loss, insomnia, constipation, and dry mouth despite recent changes in her medications. She was on treatment with escitalopram (which was gradually discontinued and replaced with mirtazapine), quetiapine, lormetazepam, and lorazepam. Imaging tests showed chronic ischemic lesions in her brain and a small meningioma, the rest of the test were normal.The initial diagnostic hypothesis was a bipolar depressive episode, and her treatment was adjusted accordingly. She was started on lithium, and her quetiapine dosage was increased, along with the anxiolytic lorazepam. Due to the persistence of depressive symptoms, including low mood, anhedonia, apathy, and negative thoughts, she was also prescribed antidepressant medication (venlafaxine and mirtazapine). Her condition gradually improved, with better eating and sleep patterns, increased participation in activities, and reduced somatic complaints and anxiety.As she continued to experience somnolence and decreased morning energy, her antipsychotic medication was switched from quetiapine to lurasidone. The dose of lithium was decreased due to tremors in her extremities, although they remained within the therapeutic range. Despite these adjustments, her mood significantly improved, and she showed no signs of worsening or psychotic symptoms, leading to her discharge.ConclusionsSummarizing different studies, LOBD who develop mania for the first time at an advanced age (≥ 50 years) constitute 5-10% of all BD. It is important to perform a thorough differential diagnosis, as an organic substrate and diverse etiologies may be present. Current guidelines recommend that first-line treatment of OABD should be similar to that of BD in young patients, with careful use of psychotropic drugs.Disclosure of InterestNone Declared

Serum Lithium Concentration and the Risk of Chronic Kidney Disease

IntroductionLithium is an important treatment option for individuals with mood disorders, but its use has been linked to the development of chronic kidney disease (CKD). Existing studies on this association have reported conflicting results.ObjectivesThe aim of this study was to examine the risk of developing CKD with lithium use adjusting for common comorbidities.MethodsThis was a retrospective cohort study that included all individuals in Iceland receiving lithium therapy between 2008 and 2018. Lithium use was defined as at least one dispensed prescription for Lithium or at least one serum lithium concentration above the detection limit. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. CKD stages 3-5 were defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the serum creatinine (SCr) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid diseases were defined based on ICD-9 and ICD-10 codes. Individuals with fewer than 2 SCr measurements during the study period and those with CKD stages 3-5 prior to 2008 were excluded. Cox regression analysis with time dependent variables was performed to assess the risk of CKD.ResultsThe study included 2046 individuals exposed to lithium, of whom 221 (10.9%) developed CKD in the study period. Among the 1220 control subjects, 39 (3.2%) developed CKD. Lithium use was associated with CKD (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.37–2.74) after adjusting for sex, age, and comorbid diseases. Other significant risk factors were age (per year, HR 1.03, 95% CI 1.02–1.04), initial eGFR (per mL/min/1.73 m2, HR 0.92-0.96, 95% CI 0.90–0.99), presence of diabetes (HR 1.73, 95% CI 1.15–2.48) and history of AKI (HR 1.89, 95% CI 1.32–2.70). When compared to the control group not exposed to lithium, the risk (HR) of CKD was 1.24 (95% CI 0.81–1.89), 2.88 (95% CI 1.97–4.20) and 5.23 (95% CI 3.31-8.26) for groups with a mean lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L, respectively.ConclusionsLong-term lithium therapy seems to increase the risk of CKD in a concentration-dependent manner in individuals with bipolar and unipolar mood disorders. To mitigate this risk, it is essential to monitor blood levels carefully and use doses of lithium as low as possible for adequate mood stabilization and treatment.Disclosure of InterestNone Declared

Lithium management around delivery: a retrospective observational cohort study

IntroductionDuring the perinatal period lithium is proven effective as maintenance therapy and to prevent postpartum psychosis. Pregnancy affects all aspects of kidney physiology altering the pharmacokinetics of lithium. To minimize the risk of both maternal and neonatal complications around delivery, several authors have provided clinical advice on lithium dosing around delivery: decreasing dose by 30-50%, suspend lithium therapy 24-48 hours before scheduled cesarean section or induced delivery or even discontinuing lithium after first signs of labour.ObjectivesTo evaluate the validity of these recommendations by investigating 1) maternal lithium serum concentrations changes around delivery, 2) the lithium trasplacental passage at delivery and 3) the association between neonatal lithium serum concentration at delivery and neonatal outcomes.MethodsPsychopathologically stable women with a singleton pregnancy (n=66) who used lithium around delivery, were included in this retrospective observational cohort study (HCB/2020/1305). All women were advised to suspend lithium administration at the onset of labour in the event spontaneous deliveries. Study date: demographic, psychiatric, obstetric and neonatal outcomes for each mother-infant pair obtained from the hospital medical records.Lithium serum concentrations were determined by means of an AVL 9180 electrolyte analyzer based on the ion- selective electrode (ISE) measurement principle. Limit of quantification (LoQ) was 0.20 mEq/L.ResultsThe most common psychiatric diagnosis was a bipolar disorder type I (n=54, 90%). Forty mothers (61%) were on lithium monotherapy. Mean (SD) umbilical cord and intrapartum maternal lithium serum concentration was 0.59 (0.13) mEq/L and 0.55 (0.13) mEq/L respectively. There was a strong positive correlation between umbilical cord and maternal lithium serum concentrations (Pearson correlation coefficient 0.95 (95%IC: 0.91,0.97). In a subsample (N=22) a paired t test indicates that the maternal serum lithium concentrations at delivery were significantly lower (mean difference=0.19 mEq/L, 95%CI=0.13-0.25) than those during obtained the day before delivery hospitalization, after a mean (SD) of 31.29 (±11.92) hours (SD=11.92) have elapsed since the taking the last dose of lithium prior to delivery. Four women (6%) relapsed early postpartum.There were no significant differences between lithium monotherapy (N=18/40) and polytherapy (N=11/26) groups with regard to acute neonatal complications (p>0.05). The only acute neonatal complication associated to umbilical cord lithium serum concentration was hypotonia [0.712 (0.298) vs. 0.534 (0.214) (F=5.065; df=1,60; p=0.028)].ConclusionsWhen lithium is used around delivery, maternal and neonatal well-being can be maximized by maintaining maternal serum lithium concentrations at the minimal effective level and discontinuing briefly when presenting to hospital for delivery.Disclosure of InterestNone Declared

Lithium Intoxication with Therapeutic Doses Following Laparoscopic Sleeve Gastrectomy: A Case Report and Review of the Literature

Introduction Lithium is a mood stabilizer often used as a first-line treatment for bipolar disorder. Its narrow therapeutic window and changes in the absorption, distribution, and elimination of the drug following bariatric surgery have important implications regarding patient safety.ObjectivesWe present a 51-year-old female patient with bipolar disorder and a medical history of morbid obesity, type 2 diabetes mellitus, hypothyroidism, hyperlipidemia, and essential hypertension. She was mentally stable on lithium 1200 mg/day, valproate 500 mg/day, and quetiapine 400 mg/day. She had undergone laparoscopic sleeve gastrectomy. After a month, she showed up to the emergency room (ER) with nausea, vomiting, diarrhea, and fatigue. Gastroenteritis was suspected until the patient started showing neurological symptoms such as delirium, dysarthria, ataxia, chorea, and athetosis.MethodsThe patient was monitored and received aggressive intravenous hydration (3000 cc of 0.9% serum isotonic) in the intensive care unit (ICU). She was prescribed intramuscular biperiden injection of 5 mg/ml/day, pheniramine 45.5 mg/2 ml/day, and lorazepam 1 mg/day. Her lithium levels were checked every six hours. She was agitated and disoriented for the first five days despite lithium levels being in the therapeutic range. On day six, her blood lithium levels dropped to 0.399 mmol/L. Her psychiatric examination revealed that she resumed cooperation and orientation, her dysarthria subsided. However, her thought content and attitude were grandiose, and she had a labile affect. We prescribed 5 mg/day of olanzapine routinely and 1 mg/day of lorazepam on a needed basis. The next day, her labile affect became calmer, and her sleep improved so she was discharged from the ICU and admitted to general surgery inpatient service, and olanzapine was titrated to 10 mg per day since she had elevated mood symptoms.ResultsAfter 7 days of intravenous hydration and supportive treatment, her neurological symptoms completely subsided except for a fine tremor, which lasted for another 3 days and then ceased. She was clinically stabilized without further need for intervention. Her lithium level was 0.206 mmol/L before her discharge.Conclusions We believe it is of utmost importance to build a consensus in guidelines and inform physicians about lithium toxicity and its symptoms after bariatric surgeries. We recommend a careful follow-up of the patient pre-and postoperatively. Preoperative psychiatric intervention includes decreasing the lithium dose gradually and discontinuing it. After the operation, lithium can be started with a much lower dose and may be increased by checking lithium levels every week for at least 6 weeks after the operation until the patient can digest solid food again, and then every 2 weeks for 6 months, and thereafter every month for one year.Disclosure of InterestNone Declared

Case Series: The use of Lithium in Bipolar Affective Disorder and End-Stage Renal Disease

IntroductionLithium is a highly effective treatment in the management of Bipolar Affective Disorder (BPAD) however it is associated with increased risk of developing chronic kidney disease. There is a lack of clear guidance on alternative approaches to managing those individuals that require cessation of lithium due to progression to end stage renal disease (ESRD).ObjectivesWe discuss two patients with BPAD on lithium therapy who have developed ESRD. In both cases, lithium was discontinued due to ESRD, with alternatives trialled. In one case, the patient continues to be managed without lithium, whereas in the second, a decision was made to recommence lithium at a low dose. We reviewed the literature to provide meaningful context to the cases.MethodsCase 1 This patient with a long history of BPAD and multiple medical co-morbidities experienced progressive decline in renal function. A decision was made to cease lithium therapy with close monitoring for signs of affective relapse. The patient was stabilised using a combination of sodium valproate and quetiapine. Since cessation of lithium, the patient has required a significant increase in support from the CMHT and more frequent admissions to manage mood and anxiety symptoms that cause significant subjective distress.Results Case 2 This patient had a long history of stable BPAD, with no episodes of illness for over 30 years. Unfortunately they developed CKD and despite a significant reduction in lithium over time, they developed ESRD requiring haemodialysis. Lithium was discontinued leading to a manic relapse of BPAD requiring a prolonged admission and a combination of carbamezapine, olanzapine, escitalopram and clonazepam to stabilise their mental state. Following discharge home, their mental state failed to reach baseline and they reported significant anxiety symptoms and memory impairment. Following protracted assessment and support they were deemed unfit for renal transplant and a decision was then made by the patient, their family, nephrology and psychiatry to recommence lithium therapy whilst on haemodialysis. Their anxiety and functioning improved significantly following the reintroduction of low dose lithium, allowing the withdrawal of other neuroleptics.ConclusionsBoth cases required an individual approach to balance physical and mental health considerations. There are no clear markers to predict if a patient will respond to alternative mood stabilisers, nor is there a guarantee that kidney function will improve or stop declining when lithium is discontinued. Decisions should reflect patient preference and balance risks associated with relapse and of declining ESRD.Disclosure of InterestNone Declared