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Using lithium safely.

Lithium is a difficult drug to use. Although it is effective in the management of mania, manic-depressive illness and recurrent depression, its unwanted effects are troublesome and the dose needs to be titrated against measurements of blood levels. With care, however, the risks can be minimized. Here we discuss lithium and approaches to optimize its use.

Antimanic Agents↗

Best practice in primary care pathology: review 5.

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.

Antimanic Agents↗

Chronic lithium nephropathy: MR imaging for diagnosis.

PURPOSE: To evaluate the appearance of lithium nephropathy at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Sixteen patients with renal insufficiency and clinical and laboratory evidence of nephropathy secondary to therapy with lithium salts were examined with a 1.5-T MR imaging unit with T1-weighted, T2-weighted fast imaging with steady-state precession (true FISP), rapid acquisition with relaxation enhancement, half-Fourier turbo spin-echo, and gadolinium-enhanced (FISP three-dimensional MR angiographic) sequences. Renal size and the presence, number, location and size of parenchymal cysts were analyzed. The cysts in each kidney were defined as rare (fewer than 10 cysts), sparse (between 10 and 30 cysts), abundant (30-60 cysts), or very abundant (more than 60 cysts). RESULTS: The mean length of both kidneys was 104 mm +/- 9 in seven cases, and one or both kidneys were less than 90 mm in length in nine cases. Renal microcysts measuring from 1 to 2 mm were detected in all patients. They were either very abundant (n = 12), abundant (n = 2), or sparse (n = 2). The cysts were located with equal abundance in both the cortex and the medulla in 11 cases and were predominantly located in the renal cortex in five cases. No renal artery stenosis was present. CONCLUSION: Microcysts secondary to long-term lithium therapy can be detected with MR imaging.

Aged↗

[Lithium: 55 years of history in the therapy of bipolar affective disorder].

The clinical history of lithium began in mid-19th century when it was used to treat gout. It was subsequently administered as a substitute for sodium chloride and towards the end of 1940 its effects for the control of mania were discovered. At present it is used effectively for treatment of mania and for the prophylaxis of bipolar disorder. Though its effect on affective illnesses is evident, the same cannot be said of its mechanism of action, since in spite of the numerous studies performed to date it is still not known exactly how this ion acts. Many theories have been proposed, the most important of which are: normalisation of possible ionic alterations; interactions with the adenylyl cyclase cAMP system; effects on the phosphatidylinositol cycle; stabilisation of the levels of neuroprotective proteins; normalisation of the values of some cytosolic endopeptidases; etc. In any case, it has yet to be determined which of these is the principal factor responsible for lithium's therapeutic action, while at the same time the possibility cannot be totally ruled out that its precise mechanism of action is still to be discovered.

Animals↗

Phase evolution, characterization, and impedance spectroscopic analysis of nanocrystalline SrBi2Nb2O9 in glassy Li2B4O7 matrix.

Transparent glass composites in the system (100 - x) Li2B4O7 - x SrBi2Nb2O9 (where x = 5, 10, 15, 20, 25, and 30, in molar ratio) were fabricated by conventional melt-quenching technique. The amorphous nature of the as-quenched glass composites was confirmed via X-ray powder diffraction (XRD) studies. Differential thermal analyses (DTA) established the glassy nature of the as-quenched samples. Glass nanocomposites (GNC's) with high-optical transparency were obtained by controlled heat-treatment of the glass composites at 750 K/6 h. Perovskite SrBi2Nb2O9 (SBN) phase formation through an intermediate fluorite phase was confirmed by XRD and transmission electron microscopy (TEM). The dielectric constant (epsilon r) in the frequency range from 100 Hz to 40 MHz at room temperature increases whereas dielectric loss (D) decreases with increase in SBN content in Li2B4O7 glass matrix. Impedance spectroscopy employed to rationalize the electrical behavior of the as-quenched glasses and glass nanocomposites suggests the coexistence of electronic and ionic conduction in these materials. The optical transmission and band-gap energy of these composites were found to be crystallite size dependent.

Bismuth↗

Lithium fluoride as a novel X-ray image detector for biological mu-world capture.

X-ray microradiographs of small biological objects, such as animals and plant materials at micrometric resolution, are currently performed by various methods, all of which are limited by the resolution or the dynamic range of the image detectors. Here a novel X-ray image detector is discussed, in which the previous limitations have been overcome. A film of lithium fluoride salt is used as a detector, in which the stored biological image is read by observing the optically stimulated visible luminescence of the active color centers, efficiently produced by the X-rays.

Animals↗

Nanomaterials for lithium-ion rechargeable batteries.

In lithium-ion batteries, nanocrystalline intermetallic alloys, nanosized composite materials, carbon nanotubes, and nanosized transition-metal oxides are all promising new anode materials, while nanosized LiCoO2, LiFePO4, LiMn2O4, and LiMn2O4 show higher capacity and better cycle life as cathode materials than their usual larger-particle equivalents. The addition of nanosized metal-oxide powders to polymer electrolyte improves the performance of the polymer electrolyte for all solid-state lithium rechargeable batteries. To meet the challenge of global warming, a new generation of lithium rechargeable batteries with excellent safety, reliability, and cycling life is needed, i.e., not only for applications in consumer electronics, but especially for clean energy storage and for use in hybrid electric vehicles and aerospace. Nanomaterials and nanotechnologies can lead to a new generation of lithium secondary batteries. The aim of this paper is to review the recent developments on nanomaterials and nanotechniques used for anode, cathode, and electrolyte materials, the impact of nanomaterials on the performance of lithium batteries, and the modes of action of the nanomaterials in lithium rechargeable batteries.

Electric Power Supplies↗

Mapping canonical Wnt signaling in the developing and adult retina.

PURPOSE: The role of the Wnt[b]/beta-catenin-dependent pathway (canonical Wnt pathway) in the context of retinal development and homeostasis is largely unknown. This study was undertaken to characterize activation of the Wnt canonical pathway and its relevance to cell type populations in the developing and adult retina. METHODS: Tissue from TCF/Lef-LacZ (T-cell-specific transcription factor/lymphoid enhancer-binding factor) transgenic mice was used for monitoring the activation of the canonical Wnt pathway. Lithium (Li(+)) treatment was applied to induce ectopic activation of the TCF/Lef-LacZ reporter gene in retinal explants. Gene expression and retinal cell types were examined by in situ hybridization (ISH) or by immunohistochemistry (IHC). RESULTS: On Li(+) treatment, ectopic expression of the TCF/Lef-LacZ reporter gene was rapidly and dramatically induced in retinal explants. The pattern of TCF/Lef-LacZ reporter gene expression was dynamic throughout retinal development and in the adult retina. There was a distinctive expression pattern in each cellular layer, in the developing ciliary margin (CM), and the prospective ciliary epithelium. In the mature retina, the TCF/Lef-LacZ reporter gene was expressed in subsets of retinal ganglion cells (RGCs) and amacrine cells. The expression of the four TCF/Lef transcription factors overlapped with activation of the TCF/Lef-LacZ reporter. CONCLUSIONS: The TCF/Lef-LacZ transgene is a faithful reporter of canonical Wnt signaling in the retina. The pattern of TCF/Lef-LacZ reporter gene activation and of TCF/Lef transcription factor expression suggests that activation of the canonical Wnt pathway is developmental-stage dependent and is spatially modulated. Our findings also imply the involvement of this pathway in the specification and/or generation of ciliary epithelium, cellular differentiation, axon guidance, and connectivity to targets in the central nervous system and in the maintenance or function of specific retinal neurons in the adult.

Animals↗

Pharmacological Treatment Patterns at Study Entry for the First 500 STEP-BD Participants.

OBJECTIVE: This study assessed patterns of psychopharmacological treatment for bipolar disorder. METHOD: Intake treatment data were examined for the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study (1998 to 1999). Diagnoses were assessed by using the Structured Clinical Interview for DSM-IV mood modules. Data on treatments were obtained by interviewing patients during the initial psychiatric examination. RESULTS: Of the 500 participants, 73.6 percent had bipolar I disorder, 23.0 percent had bipolar II disorder, and 3.4 percent had bipolar disorder not otherwise specified. Upon examination, 63.4 percent were euthymic, 24.6 percent were depressed, and 12.0 percent were experiencing manic, hypomanic, or mixed states. Standard mood stabilizers (lithium, valproate, or carbamazepine) were the most commonly prescribed class of drugs that participants were taking at intake (71.9 percent). The next most common class of agents was antidepressants (40.6 percent), followed by novel anticonvulsants (31.8 percent), second-generation neuroleptics (27.2 percent), and benzodiazepines (25.0 percent). Eleven percent of patients were treated with standard mood stabilizer monotherapy. These prescribing patterns were further analyzed by subtype of illness and compared with patterns in other clinical and community settings. CONCLUSION: In a large, well-characterized cross-sectional analysis of prescription patterns in the U.S. psychiatric academic setting, patients with bipolar disorder were primarily treated with standard mood stabilizers, followed by moderate use of antidepressants, novel anticonvulsants, and second-generation neuroleptics. Results can be useful in understanding the current clinical standard of care, as well as in guiding research studies toward areas in which there is a relative absence of evidence to inform clinical practice. Studies of longitudinal prescribing patterns in bipolar disorder are also needed.

Academic Medical Centers↗

Racial differences in medication switching and concomitant prescriptions in the treatment of bipolar disorder.

OBJECTIVE: This study examined whether the practices of switching between classes of medications and prescription of concomitant medications differed between black and non-black patients with bipolar disorders. METHODS: In a retrospective cohort design, data from 1998 to 2004 for patients with diagnoses of bipolar disorders were obtained from a large claims database. Information was obtained on the number of prescriptions for four classes of medications (anticonvulsants, mood stabilizers, and first- and second-generation antipsychotics) as well as on medication switching (between drug classes), concomitant prescriptions, resource use, and outcomes (an emergency department visit or a hospitalization). Logistic models assessed the relationship between outcomes and switching or concomitant prescriptions. RESULTS: The study population consisted of 1,113 adults who received at least one prescription from the four drug classes. Medication switching or concomitant prescriptions were documented for more than one-third of patients (36.6 percent). A significantly greater proportion of black patients received two or more medications from different drug classes (41.1 compared with 34.7 percent). The number of prescriptions was lower for black patients than for non-black patients. Patients for whom switching or concomitant prescriptions were documented were significantly more likely to have an emergency department visit or a hospitalization, and race was a significant predictor of these outcomes. CONCLUSIONS: The prevalence of polypharmacy-medication switching and concomitant prescriptions-was high among patients with bipolar disorder, with a higher prevalence among black patients. Patients who experienced switching or concomitant prescriptions were more likely to visit the emergency department or to be hospitalized.

Adult↗

Lithium: a review of its metabolic adverse effects.

Treatment with lithium has long been recognized to be associated with metabolic adverse effects notably hypothyroidism, hyperparathyroidism, weight gain and nephrogenic diabetes insipidus. It is important that clinicians prescribing lithium are aware of these adverse effects and have a strategy for their detection and management. We review aspects of these actions of lithium including their prevalence, risk factors, biochemical changes involved and management, and discuss some advances that have been made in their understanding in recent years.

Diabetes Insipidus, Nephrogenic↗

Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

Antipsychotic Agents↗

Lithium revisited.

OBJECTIVE: To review lithium's utility in the treatment of mood disorders. METHOD: We reviewed the safety, tolerability, teratogenicity, optimal dosing regimens, and mortality-lowering effects of lithium. Clinical relevance and scientific rigour determined which articles we selected for review. RESULTS: Lithium is the paradigmatic treatment for bipolar disorder (BD). In treating BD, optimal maintenance plasma levels may be approximately 0.75 to 0.85 mEq/L. Although nephrogenic diabetes insipidus is not uncommon, irreversible renal failure due to lithium appears to be a rare, idiosyncratic event. Lithium-induced cardiovascular teratology appears to be less common than previously thought. Optimal lithium dosing may be once daily, this agent appears to bestow a robust suicide-lowering effect, and emerging data hint at neurotrophic and neuroprotective effects. CONCLUSION: Lithium remains an effective and integral agent in the treatment of BD. Its ability to lower suicide rates in persons with BD warrants clinical attention.

Adverse Drug Reaction Reporting Systems↗