Search

The article reviews examples where additional focus or training is needed to optimize pharmacological treatments of schizophrenia. These include the use of hierarchical approach to treatment planning, making the therapeutic relationship with patients a priority, and embracing expertise in pharmacological management.

Aims: Norway and Sweden had different early pandemic responses that may have impacted mental health management. The aim was to assess the impact of the early COVID‐19 pandemic on mental health‐related care. Methods: We used national registries in Norway and Sweden (1 January 2018–31 December 2020) to define 2 cohorts: (i) general adult population; and (ii) mental health adult population. Interrupted times series regression analyses evaluated step and slope changes compared to prepandemic levels for monthly rates of medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, lithium, opioid analgesics, psychostimulants), hospitalizations (for anxiety, bipolar, depressive/mood, eating and schizophrenia/delusional disorders) and specialist outpatient visits. Results: In Norway, immediate reductions occurred in the general population for medications (−12% antidepressants to −7% hypnotics/sedatives) except for antipsychotics; and hospitalizations (−33% anxiety disorders to −17% bipolar disorders). Increasing slope change occurred for all medications except psychostimulants (+1.1%/month hypnotics/sedatives to +1.7%/month antidepressants); and hospitalization for anxiety disorders (+5.5%/month), depressive/mood disorders (+1.7%/month) and schizophrenia/delusional disorders (+2%/month). In Sweden, immediate reductions occurred for antidepressants (−7%) and opioids (−10%) and depressive/mood disorder hospitalizations (−11%) only with increasing slope change in psychostimulant prescribing of (0.9%/month). In contrast to Norway, increasing slope changes occurred in specialist outpatient visits for depressive/mood disorders, eating disorders and schizophrenia/delusional disorders (+1.5, +1.9 and +2.3%/month, respectively). Similar changes occurred in the pre‐existing mental health cohorts. Conclusion: Differences in early COVID‐19 policy response may have contributed to differences in adult mental healthcare provision in Norway and Sweden. [ABSTRACT FROM AUTHOR]

Bipolar disorder is associated with increased rates of many physical disorders, but the effects of medication are unclear. We systematically investigated the associations between sustained use of first line maintenance agents, lithium versus lamotrigine and valproate, and the risk of physical disorders using a nation-wide population-based target trial emulation covering the entire 5.9 million inhabitants in Denmark. We identified two cohorts. Cohort 1: patients with a diagnosis of bipolar disorder prior to first purchase (N = 12.607). Cohort 2: all 156.678 adult patients who had their first ever purchase (since 1995) of either lithium, lamotrigine or valproate between 1997 and 2021 regardless of diagnosis. Main analyses investigated the effect of sustained exposure defined as exposure for all consecutive 6-months periods during a 10-year follow-up. Outcomes included a diagnosis of incident stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, myxedema, osteoporosis, dementia, Parkinson's disease, chronic kidney disease and cancer (including subtypes). In both Cohorts 1 and 2, there were no systematic statistically significant differences in associations between sustained use of lithium versus lamotrigine and valproate, respectively, and any physical disorder, including subtypes of disorders, except myxedema, for which exposure to lithium increased the absolute risk of myxedema with 7–10 % compared with lamotrigine or valproate. In conclusion, these analyses emulating a target trial of "real world" observational register-based data show that lithium does not increase the risk of developing any kind of physical disorders, except myxedema, which may be a result of detection bias. [ABSTRACT FROM AUTHOR]

Background: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. Content: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Conclusions: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately. [ABSTRACT FROM AUTHOR]

Immune imbalances are associated with the pathogenesis and pharmacological efficacy of bipolar disorder (BD). The underlying mechanisms remain largely obscure but may involve immunometabolic dysfunctions of T-lymphocytes. We investigated if inflammatory cytokines and the immunometabolic function of T-lymphocytes, including frequencies of subsets, mitochondrial mass (MM), and low mitochondrial membrane potential (MMPLow) differed between BD patients (n = 47) and healthy controls (HC, n = 43). During lithium treatment of hospitalized patients (n = 33), the association between weekly T-lymphocyte immune metabolism and clinical symptoms was analyzed, and preliminary explorations on possible mechanisms were conducted. In comparison to HC, BD patients predominantly showed a trend toward CD4+ naïve T (Tn) activation and exhibited mitochondrial metabolic disturbances such as decreased MM and increased MMPLow. Lower CD4+ Tn-MM correlated with elevated IL-6, IL-8, and decreased IL-17 A in BD patients. With lithium treatment effective, MM of CD4+ T/Tn was negatively correlated with depression score HAMD. When lithium intolerance was present, MM of CD4+ T/Tn was positively correlated with depression score HAMD and mania score BRMS. Lithium does not mediate through the inositol depletion hypothesis, but the mRNA level of IMPA2 in peripheral blood is associated with mitochondrial function in CD8+ T cells. The cross-sectional design and short-term follow-up meant that we could not directly examine the causality of BD and immune dysregulation. The altered metabolism of CD4+ Tn was strongly associated with remodeling of the inflammatory landscape in BD patients and can also be used to reflect the short-term therapeutic effects of lithium. [Display omitted] • Activation of circulating CD4+ naive T cells is observed in BD patients. • Lower mitochondrial mass of CD4+ naive T is a pivotal mediator mediating immune dysfunction in BD patients. • Enhancing the mitochondrial mass of naïve T-cells might be a potential therapeutic target for BD. • The emergence of drug intolerance disrupts the immunomodulatory effects of lithium on T-cells. [ABSTRACT FROM AUTHOR]

In this study, Li‐containing porous carbon materials were prepared from terephthalic acid and lithium hydroxide, and then loaded with different contents of copper oxide. After these materials were fully characterized with X‐ray diffraction, scanning electron microscope, Raman spectrum, nitrogen adsorption and desorption, and CO2‐TPD, their CO2 capture performance was measured. Results showed that the CO2 capture capacity of CuO(0.75)/LiC at 0 °C under 1 bar was as high as 142.8 mg‐CO2 g−1. However, excess CuO significantly reduced CO2 capture performance of the material. For example, the maximum adsorption capacity of CuO(2)/LiC was only 119.7 mg‐CO2 g−1. Meanwhile, with CO2/N2 mixed gas, these materials had significantly and selectively higher CO2 adsorption capacity over N2. Additionally, all of these lithium‐containing carbon‐based porous materials with supported copper oxide, including CuO(0.75)/LiC, could effectively capture CO2 with high selectivity and reproducibility. [ABSTRACT FROM AUTHOR]

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI. Method: The "Boolean logic" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar. Results: Lithium's therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor‐mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short‐ as well as long‐term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo‐cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI. Conclusion: Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI. [ABSTRACT FROM AUTHOR]

Purpose: Myelosuppressive chemotherapy-induced neutropenia (CIN) remains a major limitation of cancer treatment efficacy, necessitating very expensive supportive care. Lithium carbonate, an inexpensive drug, can increase the number of neutrophils, possibly providing an efficacious and cost-effective alternative for treating CIN. The aim of this study was to determine whether lithium therapy can attenuate chemotherapy-induced neutropenia and leukopenia in breast cancer patients. Methods: A total of 50 breast cancer patients were enrolled in this prospective, interventional, randomized, controlled, and single-blind study. The patients were divided into two groups: a control group (group 1, N = 25 patients) and a lithium-treated (treatment) group (group 2, N = 25 patients). Group 1 patients were further subclassified into a non-neutropenic control group (N = 16) and a neutropenic control (N = 9) based on the subsequent development of severe neutropenia, or not. The control group received 4 cycles of doxorubicin or epirubicin plus cyclophosphamide followed by 2 cycles of paclitaxel. The treatment group received the same regimen as the control group as well as oral lithium carbonate throughout the chemotherapy cycles. Results: The results showed that the absolute neutrophil count (ANC) was increased in the lithium-treated group, while it was markedly reduced in both the non-neutropenic and neutropenic control groups (by 55.56% and 65.42% post-4 chemotherapy cycles, and by 19.57% and 39.90% post-6 cycles, respectively). The same pattern of alterations was observed for the total white blood cell count in both the control and treatment groups. In addition, the incidence and period prevalence were greatly reduced in the lithium-treated group compared to non-neutropenic and neutropenic control groups. Conclusion: Lithium therapy ameliorated chemotherapy-induced leukopenia and neutropenia in breast cancer patients. This may provide a new strategy for cost-effective treatment of CIN, particularly in Egyptian cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: Severe polyhydramnios during pregnancy may be associated with long‐term lithium use and presents considerable challenges. This complication, which has been linked to induced nephrogenic diabetes insipidus (NDI), underscores the necessity for cautious management of pregnant women with bipolar disorder. This case report aims to elucidate the relationship between long‐term lithium use, pregnancy, and the development of severe polyhydramnios, emphasizing the importance of diagnosing NDI in order to prevent obstetric and neonatal complications. Methods: We present the case of a 42‐year‐old primigravida undergoing long‐term lithium treatment for bipolar disorder type I, who developed severe polyhydramnios at 34 weeks of gestation. Clinical data including obstetric monitoring and neonatal outcomes were analyzed. Results: This case emphasizes the need for heightened awareness and proactive measures to mitigate the risk associated with lithium treatment during pregnancy. Close monitoring and timely interventions are essential to ensure optimal outcomes for both mother and fetus. Conclusions: Our article puts forth the hypothesis that there is a link between lithium use during pregnancy and the occurrence of polyhydramnios and Nephrogenic Diabetes Insipidus (NDI), which may lead to severe obstetric and neonatal complications. This case report contributes to the limited literature on the subject and gives doctors practical advice that may help them make a better risk‐benefit analysis. Further research is warranted in order to refine risk assessment protocols and management strategies in this complex clinical scenario. [ABSTRACT FROM AUTHOR]

Introduction: Lithium has an irreplaceable role in the treatment of severe mood disorders, but declining renal function associated with its use leads to clinical dilemmas. Although not often applied, and requiring close monitoring and multidisciplinary actions, concurrent lithium and haemodialysis treatment (CLHT) is a feasible option. To our knowledge, however, there are no detailed consensus‐ or evidence‐based treatment guidelines or directives on its delivery. Methods: To fill this gap, we reviewed the literature and surveyed psychiatrists and nephrologists with experience in CLHT using a self‐designed questionnaire. Our goal was to form an integrated picture of the current knowledge and clinical practices of CLHT and formulate practical recommendations for colleagues being confronted with patients with renal dysfunction requiring lithium to help manage their mood disorder. Results: We identified 14 case reports and case series describing CLHT and one systematic review concluding CLHT to be effective. Ten nephrologists and six psychiatrists practising in the Netherlands completed our questionnaire, providing details on collaboration, lithium dosing regimens, serum level evaluations and additional amenities and services they deemed necessary during CLHT delivery. Discussion: We found that CLHT appears to be safe and effective and argue that delivery is a shared responsibility and needs continuous multidisciplinary finetuning. To facilitate delivery, we provide a flowchart for the initiation or reinstatement of lithium therapy in haemodialysis patients and a practical guide for CLHT, including an easy‐to‐use rule of thumb for calculating the lithium target dose. [ABSTRACT FROM AUTHOR]

Residual lithium compounds (RLCs) are known to form on the surface of nickel‐rich LiNi1‐x‐yCoxMnyO2 (NCM) oxides during synthesis and storage. In this study, the impact of RLCs on cathode performance in sulfide‐based all‐solid‐state batteries (ASSBs) is investigated by employing practically relevant approaches to generate (or remove) RLCs on (or from) NCM single crystal particles. It is revealed that Li2CO3 is the predominant component in samples exposed to air. Surprisingly, heat treatment at high temperatures does not remove RLCs but increases the overall RLC content, accompanied by the partial transformation of existing RLCs into Li2O. These samples exhibit compromised electrochemical performance due to asymmetric overpotential increase during cell discharge. However, it is possible to recover performance through controlled ambient air storage which enables the conversion of existing Li2O into Li2CO3 and formation of fresh Li2CO3 on the surface. Notably, the beneficial effects are not replicated with pure CO2 or moisturized air storage, emphasizing the significance of storage conditions and reaction pathways for Li2CO3 formation. This study demonstrates that removal of Li2O residuals through the formation of Li2CO3 under controlled ambient air exposure proves to be advantageous for sulfide‐based ASSBs, thereby offering valuable guidance for the development of optimized NCM‐based ASSB systems. [ABSTRACT FROM AUTHOR]

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction. [ABSTRACT FROM AUTHOR]

Background: Lithium is effective in the long-term treatment of bipolar disorder. Concerns have been raised about non-responsiveness after discontinuation and resuming previously effective lithium prophylaxis. We reviewed the available literature on this so-called lithium-discontinuation-induced treatment refractoriness (LDITR). Results: We found 11 case reports and six cohort studies including 403 patients addressing LDITR, and one nation-wide register study providing some additional data on LDITR. Pooling all cohort studies, the percentages of non-responders during re-treatment with lithium ranged from 3.6 to 27.7%, with an average of 17.3%. Non-responsiveness was associated with longer duration of lithium treatment before discontinuation, longer duration of bipolar disorder before start of lithium, faster tapering off lithium, and longer duration of discontinuation. Conclusions: There may be a subgroup in whom lithium discontinuation-induced treatment refractoriness exists. However, the vast majority of people respond when lithium is restarted. Moreover, it may be necessary to continue lithium beyond the first relapses to restore long-term prophylactic efficacy. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor, in which T precursor cells undergo malignant transformation, and the side effects and drug resistance of chemotherapy drugs are still difficult problems hindering the success of treatment. Vincristine (VCR) is a traditional chemotherapy drug for children with significant efficacy in T-ALL, but its side effects are obvious. Lithium carbonate (Li2CO3) can enhance the efficacy of other chemotherapy drugs, but studies of its combination with VCR have not been reported. The purpose of this study is to investigate the effects of Li2CO3 combined with VCR on the proliferation, apoptosis and cell cycle of two pediatric T-ALL cell lines, CCRF-CEM and Jurkat cells. The results of thiazolyl blue tetrazolium bromide (MTT) colorimetric assay showed that the viability of both cells decreased with the increase of the concentration of VCR or Li2CO3 alone, which compared with the control group (P<0.05). The survival rates of the two kinds of cells were different under the same Li2CO3 concentration (P<0.01). Compared with the VCR group, the cell viability and half maximal inhibitory concentration (IC50) values of Li2CO3 combined with VCR group were reduced in the two kinds of cells, and the coefficient of drug interaction (CDI) between Li2CO3 and VCR was less than 1. Flow cytometry showed Li2CO3 combined with VCR group had the highest proportion of G2/M and apoptotic cells of the two kinds of cells among the control, Li2CO3, VCR and, Li2CO3 combined with VCR group. And there were significant differences between Li2CO3 combined with VCR group and VCR group (P<0.05). In conclusion, our experimental results suggest that the combination of Li2CO3 and VCR inhibits of T-ALL cell proliferation, arrests the cell cycle in the G2/M phase and increases cell apoptosis, which provides a new experimental basis for the clinical treatment of pediatric T-ALL, the reduction of VCR side effects, and also new ideas for drug development. [ABSTRACT FROM AUTHOR]

Background: Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega‐analyses of prospective trials of individual participant‐level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy. Methods: Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (n = 393) were aggregated into an IPD dataset (i.e., mega‐analysis). Hierarchical log‐linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI/S) and change (CGI/C) scores, and change over time in Young Mania Rating (YMR) scores. Results: Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (b = −2.33, t = −6.68, p < 0.0001), significantly greater symptom reduction on the CGI/S across time (b = −0.414, t = −6.32, p < 0.001), and a significant improvement in CGI/C across time (b = −0.47, t = −7.43, p < 0.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (b = 0.06, t = 0.49, p = 0.62). Conclusion: Findings from this IPD mega‐analysis of bipolar II depression trials suggest a divergence from current evidence‐based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega‐analysis suggests that antidepressant monotherapy may provide superior short‐term effectiveness without clinically meaningful increase in treatment‐emergent hypomanic symptoms compared to lithium monotherapy. [ABSTRACT FROM AUTHOR]

Lithium 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. Lithium 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. 7Li-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. Lithium 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. 7Li-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. • 7Li-MRI permits direct, non-invasive, longitudinal measurement of brain lithium. • Brain lithium was detected after administration of very low dose lithium orotate. • Brain 7Li-signal was stable between two- and four-weeks of supplementation. • A subset of individuals showed notably higher brain 7Li-signal intensity. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. Methods: We included adult patients with BD‐I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. Results: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). Conclusions: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples. [ABSTRACT FROM AUTHOR]

The therapeutic response to lithium in patients with bipolar disorder is highly variable and has a polygenic basis. Genome-wide association studies investigating lithium response have identified several relevant loci, though the precise mechanisms driving these associations are poorly understood. We aimed to prioritise the most likely effector gene and determine the mechanisms underlying an intergenic lithium response locus on chromosome 21 identified by the International Consortium on Lithium Genetics (ConLi+Gen). We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg. The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium. Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies. The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption. • TMPRSS15 is a novel regulator of lithium response in patients with bipolar disorder. • It is the most likely effector gene at a known lithium response locus. • The gene encodes enterokinase (ENTK), a key modulator of intestinal absorption. • ENTK likely impacts lithium response through the modulation of lithium absorption. [ABSTRACT FROM AUTHOR]

Severe mental disorders like Schizophrenia and related psychotic disorders (SRD) or Bipolar Disorder (BD) require pharmacological treatment for relapse prevention and quality of life improvement. Yet, treatment adherence is a challenge, partly due to patients' attitudes and beliefs towards their medication. Social media listening offers insights into patient experiences and preferences, particularly in severe mental disorders. All tweets posted between 2008 and 2022 mentioning the names of the main drugs used in SRD and BD were analyzed using advanced artificial intelligence techniques such as machine learning, and deep learning, along with natural language processing. In this 15-year study analyzing 893,289 tweets, second generation antipsychotics received more mentions in English tweets, whereas mood stabilizers received more tweets in Spanish. English tweets about economic and legal aspects displayed negative emotions, while Spanish tweets seeking advice showed surprise. Moreover, a recurring theme in Spanish tweets was the shortage of medications, evoking feelings of anger among users. This study's analysis of Twitter data, while insightful, may not fully capture the nuances of discussions due to the platform's brevity. Additionally, the wide therapeutic use of the studied drugs, complicates the isolation of disorder-specific discourse. Only English and Spanish tweets were examined, limiting the cultural breadth of the findings. This study emphasizes the importance of social media research in understanding user perceptions of SRD and BD treatments. The results provide valuable insights for clinicians when considering how patients and the general public view and communicate about these treatments in the digital environment. • Social Media listening might offer insights into adherence issues in severe mental disorders. • We analyzed 893,289 tweets from 2008 to 2022 with advance artificial intelligence techniques. • Differences in mentioned drugs in English and Spanish tweets revealed distinct themes and emotions. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a broad diagnostic construct associated with significant phenotypic and genetic heterogeneity challenging progress in clinical practice and discovery research. Prospective studies of well-characterized patients and their family members have identified lithium responsive (LiR) and lithium non-responsive (LiNR) subtypes that hold promise for advancement. Method: In this narrative review, relevant observations from published longitudinal studies of well-characterized bipolar patients and their families spanning six decades are highlighted. DSM diagnoses based on SADS-L interviews were decided in blind consensus reviews by expert clinicians. Genetic, neurobiological, and psychosocial factors were investigated in subsets of well-characterized probands and adult relatives. Systematic maintenance trials of lithium, antipsychotics, and lamotrigine were carried out. Clinical profiles that included detailed histories of the clinical course, symptom sets and disorders segregating in families were documented. Offspring of LiR and LiNR families were repeatedly assessed up to 20 years using KSADS-PL format interviews and DSM diagnoses and sub-threshold symptoms were decided by expert clinicians in blind consensus reviews using all available clinical and research data. Results: A characteristic clinical profile differentiated bipolar patients who responded to lithium stabilization from those who did not. The LiR subtype was characterized by a recurrent fully remitting course predominated by depressive episodes and a positive family history of episodic remitting mood disorders, and not schizophrenia. Response to lithium clustered in families and the characteristic clinical profile predicted lithium response, with the episodic remitting course being a strong correlate. There is accumulating evidence that genetic and neurobiological markers differ between LiR and LiNR subtypes. Further, offspring of bipolar parents subdivided by lithium response differed in developmental history, clinical antecedents and early course of mood disorders. Moreover, the nature of the emergent course bred true from parent to offspring, independent of the nature of emergent psychopathology. Conclusions: Bipolar disorders are heterogeneous and response to long-term lithium is associated with a familial subtype with characteristic course, treatment response, family history and likely pathogenesis. Incorporating distinctive clinical profiles that index valid bipolar subtypes into routine practice and research will improve patient outcomes and advance the development and translation of novel treatment targets to improve prevention and early intervention. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neuronal disorder that leads to the development of dementia. Until nowadays, some therapies may alleviate the symptoms, but there is no pharmacological treatment. Microdosing lithium has been used to modify the pathological characteristics of the disease, with effects in both experimental and clinical conditions. The present work aimed to analyze the effects of this treatment on spatial memory, anxiety, and molecular mechanisms related to long-term memory formation during the aging process of a mouse model of accelerated aging (SAMP-8). Female SAMP-8 showed learning and memory impairments together with disruption of memory mechanisms, neuronal loss, and increased density of senile plaques compared to their natural control strain, the senescence-accelerated mouse resistant (SAMR-1). Chronic treatment with lithium promoted memory maintenance, reduction in anxiety, and maintenance of proteins related to memory formation and neuronal density. The density of senile plaques was also reduced. An increase in the density of gamma-aminobutyric acid A (GABAA) and α7 nicotinic cholinergic receptors was also observed and related to neuroprotection and anxiety reduction. In addition, this microdose of lithium inhibited the activation of glycogen synthase kinase-3beta (GSK-3β), the classical mechanism of lithium cell effects, which could contribute to the preservation of the memory mechanism and reduction in senile plaque formation. This work shows that lithium effects in neuroprotection along the aging process are not related to a unique cellular mechanism but produce multiple effects that slowly protect the brain along the aging process. [ABSTRACT FROM AUTHOR]

Background: Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. Methods: We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. Results: On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61–7.50) hyperthymic (OR,1.20; 95%CI,1.02–1.41) and irritable temperament (OR,1.28; 95%CI,1.08–1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76–0.98) and physical abuse (OR,0.83; 95%CI,0.70–0.98) were predictors of non-response. Conclusions: In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts. [ABSTRACT FROM AUTHOR]

In this research, a coated graphite polyvinyl chloride (PVC) membrane electrode was fabricated for the potentiometric determination of lithium based on 13-(3-nitrophenyl)-12H,14H-benzo[g]chromeno[2,3-b]chromene-7,12,14(13H)-trione (L) as the ionophore. The best Nernstian response was observed from the membrane composition of 31% PVC, 7% L, 2% NaTPB, and 60% dioctyl phthalate (DOP) as the plasticizer. The designed sensor showed a wide linearity over the concentration range of 1 x 10-8-1 x 10-3 M with a slope of 60.2 ± 0.3 mV decade-1, and the limit of detection (LOD) of 7.5 x 10-9 M. The selectivity of the designed sensor was investigated by the matched potential method and no serious interference was observed. The response time and life span of the electrode were 5 s and 16 weeks, respectively. The potential response of the electrode was independent of solution pH in the pH range of 3.0-12.0. The influence of the presence of organic solvents on the potential response of the electrode was also scrutinized, and the results showed that the designed sensor keeps its Nernstian behavior in solutions with 20% non-aqueous content. In the end, the electrode was successfully applied to determine lithium carbonate in tablet, urine, and serum samples with recovery% values of 96.0 to 106.33 and RSD% 1.99-4.45. [ABSTRACT FROM AUTHOR]

In recent years, the rapid development of new energy vehicles and energy storage technology, driven by the new energy industry, has led to rapid growth in lithium consumption. China has abundant lithium resources, especially in salt lake brine. Zabuye salt lake is the only salt lake in Tibet that has achieved the industrial development of lithium carbonate by using the lithium extraction technique with salinity-gradient solar pond (SGSP) so far. In this paper, the stereo-crystallization process is innovated and optimized based on an enhanced SGSP with nucleation matrix. The optimal processing parameters such as the structure design of the nucleation matrix, the spatial range of underutilized heterogeneous nucleation zone (UHNZ), and the appropriate area ratio of crystallization units have been obtained by experiments. The results show that the UHNZ should be about 0.80–2.00 m from the bottom of the pond, when the total depth of water body in the solar pond is controlled within 2.80–3.30 m and the thickness of the freshwater layer is between 0.30 and 0.60 m. For the best precipitation effect of lithium carbonate, it is suggested that the height of lower nucleation matrix (LNM) in the crystallization unit should be controlled above the height of about 0.80 m from the bottom of the pond, and the area ratio of crystallization units should be about 10%, when implementing the stereo-crystallization process. In 2022, the stereo-crystallization process with the enhanced SGSP has been fully promoted and implemented in Zabuye mining area of Tibet, increasing the output and grade of lithium concentrates significantly. [ABSTRACT FROM AUTHOR]

Key Clinical Message: COVID‐19 infection may increase the likelihood of neutropenia in patients already on clozapine. In clozapine treated patients experiencing COVID‐19 associated neutropenia, adjunct therapy with lithium can be considered. [ABSTRACT FROM AUTHOR]

Key Clinical Message: While intermittent hemodialysis (HD) is the most efficient method of removing lithium in patients with lithium toxicity, continuous renal replacement therapy is an acceptable alternative in the setting of intradialytic hypotension. This form of dialysis can reduce the need for vasopressors during HD, which increases mortality. [ABSTRACT FROM AUTHOR]

Rationale: In bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment. Objectives: We hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes. Results: We genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers. Conclusions: Our study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium's immunomodulatory potential. [ABSTRACT FROM AUTHOR]

Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment. [ABSTRACT FROM AUTHOR]

Introduction: Lithium use during pregnancy reduces the risk of mood episodes in the perinatal period for women with bipolar disorder. Some previous studies found deleterious effects of intrauterine lithium exposure on birth outcomes, yet little is known about a dose response relationship. The current study investigated the influence of maternal lithium serum levels on birth outcomes. Methods: This retrospective observational cohort study included women with a bipolar spectrum disorder who were referred to a specialized psychiatric and obstetric outpatient clinic from 2003 to 2019 and used lithium during the entire pregnancy. For 101 pregnancies at least one lithium level during pregnancy was available. A weighted average lithium level was calculated for the entire pregnancy, as well as for each trimester. Detailed information on maternal, obstetric and neonatal outcomes were retrieved from the medical records. Linear and logistic regression models were used to investigate the association between weighted average lithium level and pregnancy duration, birth weight percentiles, preterm birth and large for gestational age births (LGA). In subsequent exploratory analyses, we studied the role of thyroid‐stimulating hormone (TSH) and thyroxine (T4) as a mediator in the found associations. Results: The weighted average lithium serum level during pregnancy was negatively associated with pregnancy duration and positively with preterm birth, but not with birth weight percentile or LGA. In exploratory analyses, TSH and T4 did not mediate the association between average lithium serum level and pregnancy duration. Conclusion: The results of this cohort study during pregnancy indicate a dose response relationship between maternal lithium serum levels and pregnancy duration. [ABSTRACT FROM AUTHOR]

Background: The phenomenon of preventing the recurrences of mood disorders by the long-term lithium administration was discovered sixty years ago. Such a property of lithium has been unequivocally confirmed in subsequent years, and the procedure makes nowadays the gold standard for the pharmacological prophylaxis of bipolar disorder (BD). The efficacy of lithium prophylaxis surpasses other mood stabilizers, and the drug has the longest record as far as the duration of its administration is concerned. The continuation of lithium administration in case of good response could be a lifetime and last for several decades. The stability of lithium prophylactic efficacy in most patients is pretty steady. However, resuming lithium after its discontinuation may, in some patients, be less efficient. Main body: In the article, the clinical and biological factors connected with the prophylactic efficacy of long-term lithium administration are listed. Next, the adverse and beneficial side effects of such longitudinal treatment are presented. The main problems of long-term lithium therapy, which could make an obstacle to lithium continuation, are connected with lithium's adverse effects on the kidney and, to lesser extent, on thyroid and parathyroid functions. In the paper, the management of these adversities is proposed. Finally, the case reports of three patients who have completed 50 years of lithium therapy are described. Conclusions: The authors of the paper reckon that in the case of good response, lithium can be given indefinitely. Given the appropriate candidates for such therapy and successful management of the adverse effects, ultra-long term lithium therapy is possible and beneficial for such patients. [ABSTRACT FROM AUTHOR]

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function. [ABSTRACT FROM AUTHOR]

Disturbances in sleep and circadian rhythmicity (CR) are frequent in individuals with bipolar disorders (BD). Very few studies explored the associations between psychotropic medications and these disturbances in euthymic BD. Therefore, we aimed at exploring the associations between several classes of medications (lithium, sedative/non-sedative Atypical Antipsychotics (AAP), anticonvulsants, antidepressants, benzodiazepines) and sleep disturbances and CR dimensions in a sample of euthymic individuals with BD. We included euthymic adults with BD type 1 or 2 assessed with 21 days of actimetry. We used a Principal Component Analysis (PCA) of sleep and CR estimates to generate dimensions to be studied in association with the current use of psychotropic medications, with adjustments for potential confounding factors. We included individuals with BD-1 (n = 116) or BD-2 (n = 37). The PCA led to four dimensions of sleep and CR estimates. Benzodiazepines were associated with better sleep quality (p corrected = 0.032). Aripiprazole was associated with less robust CR (p corrected = 0.016), but with earlier peak of activity patterns (p corrected = 0.020). Sedative AAPs were associated with better sleep quality, which was no longer significant after correction. We found no association between lithium or anticonvulsants and CR. The cross-sectional design and the possible non-representativeness of the sample were limitations of our study. In euthymic individuals with BD, benzodiazepines may have a positive effect on sleep quality, while aripiprazole may have mixed effects on CR (less robust but with earlier peak of activity patterns). No association with lithium or anticonvulsants observed. Further studies are warranted to replicate and extend these results. • Few studies explored associations between psychotropic drugs and actigraphy in BD. • Benzodiazepines are associated with higher sleep quality. • Non-sedative atypical antipsychotics are associated with less robust CR but earlier peak of activity patterns. • No association between lithium or anticonvulsants and circadian rhythms was observed. • Cross-sectional design and heterogeneity of treatment are limitations in this study. [ABSTRACT FROM AUTHOR]

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

Introduction: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. Methods: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. Results: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44–0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56–0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55–0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. Conclusion: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post‐treatment thyroid function between the two therapies. Methods: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid‐stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. Results: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one‐month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one‐month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one‐month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). Conclusion: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid. [ABSTRACT FROM AUTHOR]

Background: The extent of parathyroidectomy (PTX) recommendation in patients with lithium‐associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long‐term outcomes. Methods: A population‐based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non‐LAH). Results: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2–5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH‐group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re‐admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery. Conclusions: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence. [ABSTRACT FROM AUTHOR]

Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia. Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Conclusions: Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD. [ABSTRACT FROM AUTHOR]

This article explores the treatment of psoriasis in patients with bipolar disorder who are taking lithium. While lithium can cause or worsen psoriasis, it has traditionally been recommended to discontinue the treatment. However, recent case reports have shown success in using biologic drugs to treat psoriasis without stopping lithium. The article emphasizes the importance of collaboration between psychiatrists and dermatologists in managing this condition. It presents a case study where a patient's psoriasis improved with the introduction of a biologic drug while continuing lithium therapy, suggesting that discontinuing lithium may not be necessary. Further research is needed to develop clinical guidelines in this area. [Extracted from the article]

Background: Treatment decision‐making for individuals with bipolar disorder can be difficult. Recommendations from clinical practice guidelines can be affected by multiple methodological limitations, while pharmaco‐epidemiological data suggest great variety in prescription practices across regions. Given these inconsistencies, this study aimed to provide an alternative perspective on the effectiveness of common bipolar disorder maintenance treatments through considering naturalistic data. Methods: A total of 246 individuals with bipolar disorder (84 bipolar I [BP‐I], 162 bipolar II [BP‐II]) were recruited through clinics and/or websites. All were euthymic and had trialled at least one mood stabiliser. They completed an online survey containing questions on demographics, clinical variables, symptomatology, and the effectiveness/side effect profiles of any mood stabilisers (MSTs) or atypical antipsychotics (AAPs) that they have taken. Results: Lithium and lamotrigine were the most commonly prescribed MSTs and the most effective at mood stabilisation. Lithium and lamotrigine appeared marginally more effective for BP‐I and BP‐II respectively, however, only the latter difference was statistically significant. Furthermore, lamotrigine had the more favourable side effect profile. Amongst the AAPs, quetiapine and olanzapine were the most commonly prescribed, but they were negligibly superior to other AAPs. Conclusion: This study clearly established a preference for lamotrigine in the maintenance treatment of BP‐II. While the literature consistently emphasises the primacy of lithium in bipolar disorder treatment, its side effect profile as observed in this study remains a concern. Future research considering moderators of treatment response and concomitant medications could help to identify further nuances to consider for treatment decision‐making. [ABSTRACT FROM AUTHOR]

Background: There has been no previous study in Thailand regarding the incidence of lithium-induced abnormal renal function. Hence, this study aimed to assess the effect of lithium maintenance therapy on chronic kidney disease, and associated factors among outpatients diagnosed with a psychiatric illness within Southern Thailand. Methods: This was a retrospective study, using an information review from the electronic medical records of Songklanagarind Hospital computer system in the last ten years; from 1 January 2013 until 31 September 2022. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and persisted for three months or more. There were 461 outpatients diagnosed with a psychiatric illness who received lithium maintenance therapy. From this, 154 outpatients were excluded: 153 received lithium therapy for less than three months and 1 presented with a baseline chronic kidney disease. All data were analyzed using Rstudio 4.3.1. The incidence of lithium-induced chronic kidney disease was analyzed by survival analysis. Results: Of the 307 outpatients diagnosed with a psychiatric illness and received lithium maintenance therapy, the most common diagnosis was bipolar disorder (59.3%). Most were female (52.8%), with the median (IQR) age of 39.0 (27.5–54.0) years. The median (IQR) age onset of lithium therapy and duration of lithium maintenance therapy were 28.0 (21.0–41.5) years, and 2.97 (0.9–9.2) years, respectively. This study identified six outpatients (1.9%) that developed chronic kidney disease stage 3 or more and one of them (0.3%) presented with chronic kidney disease stage 5 or end-stage. The incidence of lithium-induced chronic kidney disease was 0.0023 cases per exposed patient-year. When comparing outpatients who had received lithium maintenance therapy and developed chronic kidney disease with those who did not develop chronic kidney disease, this study identified that most of the group with chronic kidney disease had a lithium maintenance therapy for more than ten years, had an older age onset of lithium therapy, reported history of psychiatric hospitalization and lithium intoxication, and presented with physical illness. The associated factors between the effect of lithium maintenance therapy and chronic kidney disease could not be identified due to a limited number of outpatients having developed chronic kidney disease. Conclusions: Lithium-induced chronic kidney disease was identified as a minor incidence, and it was likely safe for maintenance therapy with careful and regular monitoring. However, older patients or those receiving lithium for a longer time and present with comorbid physical illnesses should be prescribed with caution. IRB / IEC certification: 65-389-3-4. [ABSTRACT FROM AUTHOR]

We report on 6Li neutron capture therapy (LiNCT) in anticipation of using carbon nanoparticles to deliver targeted, high linear energy transfer radiation to non-resectable tumors. Our investigations show that, compared with existing 10B neutron capture therapy (BNCT), 6Li offers similar dose potential for equal mass density ( D Li ∼ D B when m Li = m B ), for capture products that span 7 times more range and approximately three cell lengths. Consequently, 6Li-filled nanoparticles dispersed more than half-a-cell-length apart, better convey high doses and ultra-high dose-rates, as LiNCT generates substantially less γ-rays and becomes more targeted than BNCT. To this end, we propose a neutron production scheme involving laser-plasma driven protons incident on various 7Li targets, capable of producing > 10 9 n /sr/pulse. For high repetition frequency, efficient neutron moderation, and ideal 6Li concentration, the modality offers greater precision than existing neutron capture therapy. [ABSTRACT FROM AUTHOR]

The use of adjunctive therapy for bipolar disorder is increasingly considered to increase the efficacy of standard treatments. In this randomized clinical trial, we evaluated the effect of vitamins B1 and B6 in separate treatment arms on mood symptoms, cognitive status, and sleep quality in hospitalized patients with bipolar disorder in manic episodes. In addition to receiving standard lithium treatment, participants (N = 66) were randomized to one of three conditions: 100 mg of vitamin B1, 40 mg of vitamin B6, or placebo. Outcomes were assessed one and 8 weeks of daily treatment, including the Young Mania Rating Scale (YMRS), Pittsburgh Sleep Quality Scale (PSQI), and Mini-Mental State Examination (MMSE). This study was performed between December 2020 and September 2021 based on the registration code number IRCT20200307046712N1. Vitamin B6 had a significant effect (P value < 0.025 as significant) on mood improvement compared to placebo (F (1, 27.42) = 30.25, P < 0.001, r = 0.72), but vitamin B1 had no significant effect on mood improvement compared to Placebo (F (1/35.68) = 4.76, P = 0.036, r = 0.34). The contrasts between groups on PSQI showed a significant effect (P value < 0.025 as significant) of vitamin B6 over placebo for sleep status improvement (F (1/32.91) = 16.24, P < 0.001, r = 0.57) and also a significant effect of vitamin B1 over placebo (F (1/41.21) = 13.32, P < 0.001, r = 0.49). The use of vitamin B6 as an adjunctive therapy to lithium can be associated with the improvement of mood symptoms in patients with bipolar disorder in the midst of a manic episode. • The use of vitamin B6 as an adjunctive therapy to lithium can be associated with the improvement of mood symptoms in patients with bipolar disorder in manic episodes. • Vitamin B6, as well as vitamin B1 as adjunctive therapy, can improve sleep quality in patients with bipolar disorder in manic episodes. [ABSTRACT FROM AUTHOR]

Background: During over half a century, science has shown that lithium is the most efficacious treatment for bipolar disorder but despite this, its prescription has consistently declined internationally during recent decades to approximately 35% ever use or less of patients with bipolar disorder. Content: This narrative review provides an overview of the decreasing use of lithium in bipolar disorder internationally, shortly summarises the evidence for lithium's acute and prophylactic effects in bipolar disorder, discuss the challenges in relation to lithium including side effects, long-term risks and myths around lithium and provides two detailed examples on how specialised care models may result in successful increase of the use of lithium to 70% of patients with bipolar disorder largescale and improve care regionally and nationally. Conclusions: Decades of scientific investigations and education and teaching of clinicians and the public has not increased the use of lithium on a population-based large scale. It is argued that lithium should be the drug of choice for maintenance therapy as the single first-line treatment and that organizational changes are needed with specialised care for bipolar disorder to systematically and long-term change the use of lithium on a large-scale population-level. [ABSTRACT FROM AUTHOR]

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O'Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use. [ABSTRACT FROM AUTHOR]

This article examines the scientific career of Edward Trautner, who did pioneering research in the 1950s on lithium treatment for psychiatric disorders. Trautner was the first scientist to study the mechanism of action of lithium as a psychiatric medication. His research established that lithium could be used safely and rationally, and anticipated by a decade the large volume of research in the 1960s and 1970s that led to international acceptance of lithium treatment for mood disorders. Trautner was a pioneer of biological psychiatry who considered pharmacology to be a useful therapeutical tool rather than a permanent cure for putative chemical imbalances. His research involved cross-disciplinary collaborations that combined clinical and laboratory research in the disciplines of psychiatry, physiology, biochemistry, teratology, and even oncology. Trautner himself had a multidisciplinary background that included publications in literature and philosophy. [ABSTRACT FROM AUTHOR]

Background. Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. Methods. This naturalistic study included 760 subjects with BD (FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. Results. Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was =0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). Conclusions. This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations. [ABSTRACT FROM AUTHOR]

This study examined the association of gender on the physical morbidity of individuals likely living with bipolar disorder (BD) using a comprehensive health-related database. It investigated the association between lithium dispensing (a surrogate marker for BD) and other health morbidities, considering age and sex. The cross-sectional study design used the 10 % Schedule of Pharmaceutical Benefits Scheme (PBS) database in Australia for 2022. Medication dispensing, age, and sex were available. A validated algorithm inferred 45 health morbidities from dispensed medicines. Statistical analyses, including logistic regression, assessed the relationship between lithium dispensing, sex, and age with inferred health morbidities. The sample consisted of 1,594,112 individuals aged 10 to over 95 years. A higher proportion of women than men were dispensed lithium (0.33 % vs 0.30 %). Lithium dispensing and age were associated with higher prevalence of inferred morbidities. Women dispensed lithium had a greater physical health burden compared to men, with higher odds of chronic airways diseases, diabetes, ischaemic heart disease/hypertension, inflammation, pain, psychosis, and steroid-responsive diseases. Conversely, women dispensed lithium had lower odds of cardiac arrhythmias and hypothyroidism compared to men. This study provides evidence that individuals with BD, indicated by the dispensing of lithium, experience a relatively higher frequency of physical health morbidities, with women being disproportionally affected compared to men. The findings highlight the need for comprehensive care for people living with BD, particularly women. • Most physical morbidities are more prevalent among individuals with than without bipolar disorder (BD), particularly women. • Women with BD have more respiratory, heart and steroid-responsive diseases, diabetes, inflammation, and pain than men. • Cardiac arrythmia and hypothyroidism are more frequent in men than women with bipolar disorder. • Older adults with BD require effective preventive interventions designed to meet their physical health, especially women. [ABSTRACT FROM AUTHOR]

Aims: Despite lithium's clinical efficacy, it is commonly thought that its use is declining. The objective of this study is to describe the new and prevalent lithium users as well as rates of discontinuation of lithium use over a 10-year period. Methods: This study used provincial administrative health data from Alberta, Canada between January 1, 2009 and December 31, 2018. Lithium prescriptions were identified within the Pharmaceutical Information Network database. Total and subgroup specific frequencies of new and prevalent lithium use were determined over the 10-year study period. Lithium discontinuation was also estimated through survival analysis. Results: Between the calendar years of 2009 and 2018, 580,873 lithium prescriptions were dispensed in Alberta to 14,008 patients. The total number of new and prevalent lithium users appears to be decreasing over the 10-year timeframe, although the decline may have stopped or reversed in the latter years of the study period. Prevalent use of lithium was lowest among individuals between the ages of 18–24 years while the highest number of prevalent users were in the 50–64 age group, particularly among females. New lithium use was lowest amongst those 65 years and older. More than 60% (8,636) of patients prescribed lithium, discontinued use during the study timeframe. Lithium users between ages of 18–24 years were at the highest risk of discontinuations. Conclusions: Rather than a general decline in prescribing, trends in lithium use are dependent on age and sex. Further, the period soon after lithium initiation appears to be a key time period in which many lithium trials are abandoned. Detailed studies using primary data collection are needed to confirm and further explore these findings. These population-based results not only confirm a decline in lithium use, but also suggest that this may have stopped or even reversed. Population-based data on discontinuation pinpoint the period soon after initiation as the time when trials are most often discontinued. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a chronic illness requiring long-term use of mood stabilizers such as lithium and sodium valproate. The adverse drug reactions (ADRs) of these medicines can severely affect the quality of life of the patients. A comparative study of ADR profile of lithium and valproate in terms of prevalence, severity, and causality has not been done in the rural population of India. Methodology: A cross-sectional, observational study was done in the psychiatry outpatient department of a tertiary health care center. The bipolar disorder patients on lithium carbonate or divalproate monotherapy were chosen for documentation of ADRs after informed consent. The Naranjo causality algorithm and Modified Hartwig and Siegel scale for severity assessment were applied to all participants. The data obtained were statistically analyzed using Epi Info open-source software. Results: The study participants having mean age of 33.83 ± 12.02 years comprised nearly equal number of males and females. Tremors (19.4%), polyuria (11.5%), and polydipsia (11.2%) were the most common ADRs due to lithium, whereas nausea (12.6%), anorexia (10.6%), and sedation (9.1%) were more commonly seen in patients on valproate. Most of the ADRs had a mild severity and were categorized as possible in the Naranjo causality algorithm. Conclusion: Although ADRs are common in bipolar disorder patients treated with lithium or valproate, they are often mild and well tolerated by the patients. [ABSTRACT FROM AUTHOR]