Article

The clinical applications of lithium orotate. A two years study

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Sixty four patients were treated with lithium orotate and observed for time periods ranging from four months to two and one half years. Lithium orotate is of truly unparalleled efficiency in the treatment of constitutional migraine, constant headache and hemicrania. Also in the treatment of depression, alcoholism and epilepsy, lithium orotate has proven very useful without any problems in the application. Lithium orotate is effective at uncommonly low dosages and causes no negative side effects. Lithium citrate and lithium carbonate are far less effective than lithium orotate. The specific principle is considered to be a directed intracellular transport of lithium by means of the orotic carrier molecule, which has a high affinity for tissue dependent on the pentose pathway, e.g., glia and the blood brain barrier. The directed carrier principle of the lithium orotate therapy makes a determination of the lithium level in blood serum unnecessary. The effectiveness of lithium therapy as such is based on a membranal and cellular displacement of sodium.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Lithium orotate was recently introduced as a drug by Nieper (1973a) who used it in clinical trials in the hope of applying the principle of directed electrolyte transport in lithium therapy. His studies on calcium orotate and magnesium orotate indicated that these salts pass through the cell membrane in undissociated form and release the respective ions only at the site of membranes of cytoplasmic structures (Nieper, 1969;1973b). ...
... His studies on calcium orotate and magnesium orotate indicated that these salts pass through the cell membrane in undissociated form and release the respective ions only at the site of membranes of cytoplasmic structures (Nieper, 1969;1973b). Nieper assumed that lithium orotate also would be taken up in the undissociated form specifically into the tissues of the central nervous system whereupon the lithium ion would be liberated within the cells (Nieper, 1973a). ...
... The features of lithium pharmacokinetics previously established using LiCl and Li2CO3, such as more rapid uptake of lithium after intraperitoneal injection than after intragastric administration (Morrison, Pritchard, Braude & D'Aguanno, 1971), higher lithium concentrations in serum than in brain soon after short-term lithium administration (Schou, 1958;Ebadi, Simmons, Hendrickson & Lacy, 1974), higher lithium concentrations in kidney and brain than in liver after longterm lithium administration (Birch & Hullin, 1972), and higher lithium concentrations in red blood cells than in plasma during prolonged administration of lithium (Smith, 1975) also were observed in the present study of LiOr. Thus, the findings offer no support whatsoever for the assumption that the pharmacokinetics of lithium ions given as LiOr differ from LiCl or Li2CO3 (Nieper, 1973a). ...
Article
Full-text available
1The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride.2No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food.3The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate.4Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion.
... There would therefore be advantages in a preparation of a lithium salt that maintains a relatively constant serum lithium concentration with as few doses as possible. Lithium orotate has been reported by Nieper (1973) to be effective at doses of 0.9 mmol lithium ion four to six times per week in cases of constitutional migraine, hemicrania, constant headache, and other disorders. In contrast to this, the correct dose of lithium carbonate for lithium prophylaxis has been recommended to be about 20 to 30 mmol lithium ion daily (Kerry, 1975). ...
... The elevated brainconcentrations after the orotate may be a consequence of the lithium serum concentrations falling off much more slowly than after the carbonate (Fig. 2). Lithium equilibrates slowly between blood and brain in contrast with the process between blood and other tissues (Schou, 1958 Nieper (1973) offered an alternative explan. ation, suggesting that orotic acid forms a complex with lithium which can enter the brain preferentially through a specific carrier mechanism for orotate. ...
Article
Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.
... Харчові отруєння літієм спостерігаються досить рідко. Інтоксикація літієм часто має ятрогенну природу (отруєння препаратами літію зустрічаються в психіатричній практиці) [13,17]. ...
... Симптомами середньої інтоксикації є діарея, блювання, м'язова слабкість, млявість і втрата координації. Симптомокомплекс тяжкого отруєння літієм складається з неврологічних розладів: атаксії, погіршення зору, втрати пам'яті, запаморочення, втрати орієнтації, судом, ступору й коми [17,19]. ...
... For the preventive treatment of mood disorders related to migraine or tension-type headache, the recommended therapy is to use antidepressive tricyclics (TCAs) [72], such as amitriptyline, as monotherapy or a combination of amitriptyline and an SSRI such as paroxetine [16] or flunarizine [73] and mood stabilizers such as lithium [21] or valproate [73,74]. These have been tested and found to be useful for migraine prophylaxis. ...
Article
Full-text available
Studies on the prevalence and impact of psychiatric disorders among headache patients have yielded findings that have clarified the relationship between migraine and major affective disorders, anxiety, illicit drug abuse, nicotine dependence, and suicide attempts. Studies in both clinical and community-based settings have demonstrated an association between migraine and a number of specific psychiatric disorders. In large-scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. In longitudinal studies, the evidence supports a bidirectional relationship between migraine and depression, with each disorder increasing the risk of the other disorder. Although a strong association has been demonstrated consistently for migraine and major depression, especially for migraine with aura, there has been less systematic research on the links between migraine and bipolar disorder. This review will focus on the way in which psychiatric disorders decrease the quality of life and result in a worse prognosis, chronicity of the disease, and a worse response to treatment. Short-term pharmaceutical care intervention improves the patients' mental health, but it does not significantly change the number and severity of headaches. The increase in self-efficacy and mental health associated with pharmaceutical care may be instrumental in improving the long-term pharmacotherapy of patients with migraine and headache.
... Further, it is also reported that lithium ions (Li + ) can increase the release of serotonin or 5-hydroxy tryptamine by neurons in the brain [5]. Furthermore, the most commonly prescribed lithium salts include lithium carbonate (Li 2 CO 3 ), lithium orotate (C 5 H 3 LiN 2 O 4 ), and lithium citrate (Li 3 C 6 H 5 O 7 ) for pharmacological treatment in mentally disordered patients [6,7]. Thus, by conceiving the usefulness of lithium in pharmaceutical industry, the present study was attempted to investigate an alternative way, which can modify the physical, atomic and thermal properties of lithium powder. ...
Data
Full-text available
Lithium has gained extensive attention in medical science due to mood stabilizing activity. The objective of the present study was to evaluate the impact of biofield treatment on physical, atomic, and thermal properties of lithium powder. The lithium powder was divided into two parts i.e., control and treatment. Control part was remained as untreated and treatment part received Mr. Trivedi’s biofield treatment. Subsequently, control and treated lithium powder samples were characterized using X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Thermogravimetric analysis-differential thermal analysis (TGA-DTA), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). XRD data showed that lattice parameter, unit cell volume, density, atomic weight, and nuclear charge per unit volume of lithium were altered after biofield treatment. The crystallite size of treated lithium was increased by 75% as compared to control. DSC analysis exhibited an increase in melting temperature of treated lithium powder upto 11.2% as compared to control. TGA-DTA analysis result showed that oxidation temperature, which found after melting point, was reduced upto 285.21°C in treated lithium as compared to control (358.96°C). Besides, SEM images of control and treated lithium samples showed the agglomerated micro particles. Moreover, FT-IR analysis data showed an alteration in absorption band (416→449 cm-1) in treated lithium sample after biofield treatment as compared to control. Overall, data suggested that biofield treatment has significantly altered the physical, atomic, and thermal properties of lithium powder.
... Lithium has been used to treat leukopenia (30) and may help mobilize hematopoietic stem cells in bone marrow transplant donors (13). Historically, lithium was thought to be beneficial for patients with hepatitis (18,27,34). The mechanism(s) of these beneficial effects of lithium has been unclear for years but has recently been attributed to the blocking of GSK3␤, a well-conserved ubiquitously expressed multitasking serine/threonine protein kinase that plays a pivotal role in multiple pathophysiological processes. ...
Article
Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long term exposure to higher psychiatric doses of lithium may be nephrotoxic, short term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets GSK3β, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact "kidney protective dose" of lithium and test the effects of low dose lithium on acute and chronic kidney disease in humans.
... Another form of lithium called lithium orotate, is preferred because the orotate ion crosses the blood-brain barrier more easily than the carbonate ion of lithium carbonate. Therefore, lithium orotate can be used in much lower doses (e.g. 5 mg) with remarkable results and no side effects [49,50]. Clinical trials involving 150 mg daily doses of lithium orotate administered 4 to 5 times a week, showed a reduction of manic and depressive symptoms in bipolar patients [50]. ...
Article
Full-text available
According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.
... In the late 1970s, King et al. [250] noted that lithium orotate resulted in greater serum and brain concentrations of elemental lithium than did equivalent lithium carbonate dosages. These increased serum concentrations may be related to reduced kidney filtration rate [251] and/or increased delivery of lithium across cell membranes as a neutral non-dissociated lithium orotate complex [252,253]. As such, lithium orotate can achieve therapeutic brain lithium concentrations at markedly reduced dosages compared to conventional lithium compounds, expanding its safety profile. ...
Article
Full-text available
North American incidence of Alzheimer's disease (AD) is expected to more than double over the coming generation. Although genetic factors surrounding the production and clearance of amyloid-β and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a "perfect storm" to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.
Article
SYNOPSIS The administration of lithium carbonate (Priadel) to five patients with classical or common migraine caused the attacks in all of them to become much more frequent and severe. This outcome contrasts with the drug's established role in cluster headache, and suggests that the Pathogeneses of these two types of pain may be different.
Article
Treating migraine requires patience and innovativeness by both patient and physician. It is essential to model the therapy to meet individual differences in general health, frequency of attacks, time of day of onset, precipitating factors, and variations in response to medications and side effects. It is advisable to combine both preventive and abortive medications with nonmedical therapy programs, including dietary, biofeedback, psychological, and relaxation methods. Prolonged, uninterrupted use of preventive medications should be discouraged, since natural remissions of migraine occur and may not be appreciated when prolonged, successful preventive therapy is continued indefinitely.
Article
This study was undertaken to estimate the prevalence of migraine in people suffering from bipolar affective disorder. a headache questionnaire incorporating the newly introduced International Headache Society (IHS) criteria was given to 117 patients on the Dunedin Bipolar Research Register. a total of 81 (69%) completed the questionnaire, out of which 21 (25.9%) reported migraine headaches. 25% of bipolar men and 27% of bipolar women suffered from migraine. these rates are higher than those reported in the general population with the rate for bipolar men being almost five-times higher than expected. An increased risk of suffering form migraine was particularly noted in bipolar patients with an early onset of the disorder. This may represent a more severe form of bipolar affective disorder.
Article
Lithium has been put to clinical trials in no less than fifteen neurological disorders. They are Huntington's chorea, tardive dyskinesia, spasmodic torticollis, Tourette's syndrome, L-dopa induced hyperkinesia and the "on-off" phenomenon in parkinsonism, organic brain disorders secondary to brain-injury, drug induced delusional disorders, migraine and cluster headache, periodic hypersomnolence, epilepsy, meniere's disease and periodic hypokalemic paralysis. This paper gives a brief summary of the clinical trials with lithium salts reported in the literature. There are encouraging results on the use of lithium in cluster headaches, cyclic form of migraine and hypomanic mood disorders due to organic brain disorders. The trials with lithium and amitriptyline in tardive dyskinesia needs independent confirmation. The effect of lithium on seizure disorders needs to be addressed too.
Article
The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere's syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Lithium hypochlorite (LiOCl), the pool and spa sanitizer/algicide, was evaluated for genotoxicity in a battery of studies designed to evaluate potential mutagenicity, DNA damage and chromosome aberrations. LiOCl was not mutagenic in the Ames test when tested in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 or in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) mutation assay in Chinese hamster ovary (CHO) cells without metabolic activation. LiOCl did not induce DNA damage in the unscheduled DNA synthesis assay using rat primary hepatocytes. Effects on metaphase chromosomes were evaluated in vitro in CHO cells at 12 and 18 h exposure without S9 and at 12 and 22 h following a 2 h exposure with S9. LiOCl induced a statistically significant increase in chromosome aberrations at the high dose only at both harvest times without S9 and at the late harvest time with S9. There were significant increases in chromosome aberrations at the low dose, low-mid and high doses, but not at the high mid-dose at the early harvest time with S9. However, LiOCl did not increase chromosome aberrations when tested orally in rats at maximally tolerated doses. Bone marrow cells, collected 6, 24 and 48 h after a single oral dose of LiOCl to rats (100, 500, 1000 mg/kg in males; 50, 250, 500 mg/kg in females) showed no increase in the incidence of aberrations. In general, the weight of the evidence indicates that LiOCl is not genotoxic.
Article
Psychotropic drugs act on multiple organ systems, but their intended action is related to their effect on neurohormones and receptors in the limbic area of the brain. These drugs are also employed with benefit in a number of diverse physical disorders including immunological (arthritis), gastrointestinal (peptic ulcer, ulcerative colitis), neurological (epilepsy), and hematological (leukopenia) conditions. While their clinical efficacy enhances our armamentarium to treat these disorders, understanding their mode of action in treating the physically ill patients may yield the missing link between the psyche and the soma.
Article
Information is sparse concerning migraine distribution in mood disorder subjects based mainly on psychiatric disorder. In a sample of 283 normothymic mood disorder outpatients on maintenance treatment with serotonin reuptake inhibitors (SSRIs) or lithium, we investigated migraine distribution and clinical variables possibly related to comorbidity risk between mood disorder and migraine. Some 26.8% of the sample met criteria for migraine with migraine age of onset earlier than mood disorder age of onset; familiarity for mood disorder and migraine was strictly related to comorbidity risk in probands. Long-term treatment with lithium salts subjectively improved migraine outcome. These results could support the bidirectional association between the two clinical forms, considering the familial and pharmacological patterns.
Article
A comprehensive overview of the clinical aspects of lithium therapy is presented. Emphasis is placed on recent developments regarding the clinical uses of Li2CO3 in non-psychiatric conditions. The established efficacy of the drug in the treatment and prophylaxis of mania and bipolar affective disorders is noted, and the evidence supporting the use of lithium salts as a prophylactic agent in unipolar depression, aggressive behavior, schizophrenic disorders and organic brain dysfunction is discussed. The use of lithium carbonate in various disorders of movement and in certain extrapyramidal diseases is summarized, as are the results of its trials in alcoholism and drug abuse. In addition, uses of Li2CO3 in asthma, thyroid diseases, granulocytopenia, headache, bowel disease, anesthesiology, cardiology, and sleep disorders are summarized. The data suggests the potential effectiveness of Li2CO3 in a variety of clinical conditions other than those for which it is classically indicated, provided more detailed double-blind studies are performed.
Article
Full-text available
Bipolar disorder (BD) poses a significant public health concern, with roughly one‐quarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li2CO3), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC5H3N2O4; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood–brain barrier and enter cells more readily than Li2CO3, which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.
Article
In addition to its well-studied use in affective disorders, lithium has been evaluated in a wide variety of other psychiatric and nonpsychiatric conditions. There are over 150 published reports of lithium trials in approximately 30 different conditions. Placebo-controlled studies have failed to confirm claims of lithium effect in premenstrual tension1-6 and have given negative results in obsessive-compulsive neurosis.7-13 Ancedotal observations have indicated positive effects in anorexia nervosa, affective psychosis in organic brain syndrome, psychoses precipitated by drugs, pathological hypersexuality, and transvestism.14-25 However, placebocontrolled studies are lacking. There have been 24 reports on the effects of lithium treatment on alcohol consumption in animals and man.26-49 Of special interest here are the two recent double-blind, placebo-controlled trials, one American35 and one British.37 The American patients suffered from "chronic alcoholism associated with nonpsychotic depression." Of the alcoholics finishing the trial, those given lithium had significantly fewer drinking
Article
A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.
Article
Lithium orotate, the salt of lithium and orotic acid, has been marketed for decades as a supplemental source of lithium with few recorded adverse events. Nonetheless, there have been some concerns in the scientific literature regarding orotic acid, and pharmaceutical lithium salts are known to have a narrow therapeutic window, albeit, at lithium equivalent therapeutic doses 5.5–67 times greater than typically recommended for supplemental lithium orotate. To our knowledge, the potential toxicity of lithium orotate has not been investigated in preclinical studies; thus, we conducted a battery of genetic toxicity tests and an oral repeated-dose toxicity test in order to further explore its safety. Lithium orotate was not mutagenic or clastogenic in bacterial reverse mutation and in vitro mammalian chromosomal aberration tests, respectively, and did not exhibit in vivo genotoxicity in a micronucleus test in mice. In a 28-day, repeated-dose oral toxicity study, rats were administered 0, 100, 200, or 400 mg/kg body weight/day of lithium orotate by gavage. No toxicity or target organs were identified; therefore, a no observed adverse effect level was determined as 400 mg/kg body weight/day. These results are supportive of the lack of a postmarket safety signal from several decades of human consumption.
Article
If a standardized program of Megavitamin Therapy (MVT) and/or Lithium Orotate Therapy (LOT) are added to programs of psychotherapy, there should be seen measurable, observable and statistical differences in before and after populations as measured by the Minnesota Multiphasic Personality Inventory (MMPI). Thirty-two subjects, in a matched group design, each were assigned to seven groups (N=224): No Treatment Group, Psychotherapy Only Group, Psychotherapy and Megavitamin Therapy Group, and the Lithium Orotate, Psychotherapy, and Megavitamin Therapy Group. The last three groups had before and after subjects. The No Treatment Group was tested and then abandoned. Each of the specific groups were administered the full MMPI both upon admission to the treatment program and at the point of discharge. These groups were balanced for sex, religion, occupation, educational level, and race. The results were statistically significant. They demonstrated that time in therapy was reduced by seven months, Megavitamin Therapy was 66% more effective than Psychotherapy Only; it was therefore cost-effective. Whereas, MVT and LOT were only 8% more effective. Introduction/Motivation for the Study During the past decade the writer has observed the most common diagnosis for his patients to be: 296.23 Major Depression, Single Episode Without Psychotic Features. The average length in therapy was twelve to eighteen months. The author, without formal train-
Article
Impaired adaptive response to oxidative injuries is a fundamental mechanism central to the pathogenesis of chronic hepatitis C (CHC). Glycogen synthase kinase (GSK) 3β is an indispensable regulator of the oxidative stress response. However, the exact role of GSK3β in CHC is uncertain and was examined. GSK3β and Nrf2 signalling pathways were examined in JFH1 HCV infected Huh7.5.1 hepatocytes, and also in liver biopsy specimens from CHC patients. HCV infection elicited prominent Nrf2 antioxidant response in hepatocytes, marked by elevated expression of the Nrf2-dependent molecule haem oxygenase-1 and subsequent protection from apoptotic cell death. Inhibitory phosphorylation of GSK3β seems to be essential and sufficient for HCV-induced Nrf2 response. Mechanistically, GSK3β associated and physically interacted with Nrf2 in hepatocytes. In silico analysis revealed that Nrf2 encompasses multiple GSK3β phosphorylation consensus motifs, denoting Nrf2 as a cognate substrate of GSK3β. In the presence of TGFβ1, the HCV-induced GSK3β phosphorylation was blunted via a protein phosphatase 1-dependent mechanism and the cytoprotective Nrf2 response drastically impaired. This effect was counteracted by lithium, a selective inhibitor of GSK3β. In liver biopsy specimens from CHC patients, the expression of phosphorylated GSK3β positively correlated with Nrf2 expression and was inversely associated with the degree of liver injury. Moreover, CHC patients who received long-term lithium carbonate therapy primarily for concomitant psychiatric disorders exhibited much less liver injury, associated with enhanced hepatic expression of Nrf2. Inhibition of GSK3β exerts hepatoprotection in CHC possibly through its direct regulation of Nrf2 antioxidant response.
Chapter
In Chapter 26, the requirements of an ideal lithium preparation have been outlined, and the question naturally arises as to which of the many lithium preparations currently available most nearly conforms to the criteria enunciated in that chapter. This question is not, unfortunately, one which is easily answered.
Chapter
Although lithium was originally introduced for the treatment of acute manic-depressive illness, it has been tried in many other psychiatric disorders, particularly during the last 15 years. All the major lithium textbooks published during the last 10 years1–6 contain detailed multi-author accounts of the various clinical and experimental uses of lithium. Jefferson and Greist7 provide a unified view for the practicing physician, and the treatment of mania and acute depression and the prophylactic uses of lithium are reviewed by Coppen et al.8 The role of lithium in psychiatric disorders not clearly related to manic-depressive illness is still being evaluated,9 and the therapeutic efficacy of lithium in many nonpsychiatric disorders has also been discussed.10 Results in this area are often difficult to assess, since many studies consist of only anecdotal reports.
Article
Background Lithium as a mood stabilizer has been used as the standard pharmacological treatment for bipolar disorder (BD) for more than 60 years. Recent studies have also shown that it has potential for treatment of many other neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease, through its neurotrophic, neuroprotective, antioxidant and anti-inflammatory actions. Therefore, exploring its pharmacokinetic features and designing more excellent lithium preparations are becoming important research topics. Methods We reviewed many studies on the pharmacokinetics, drug design and toxicity of lithium based on recent relevant research progress from PubMed, Web of Science, Elsevier and Springer databases. Keywords used for searching references were lithium, pharmacology, pharmacokinetics, drug design and toxicity. Results Lithium is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Its level is initially highest in serum and then is evidently redistributed to various tissue compartments. It is not metabolized and over 95% of lithium is excreted unchanged through the kidney, but different lithium preparations may have different pharmacokinetics features. Lithium has a narrow therapeutic window limited by various adverse effects, but some novel drugs of lithium may overcome these problems. Conclusion Various formulations of lithium have potential for treating neurodegenerative brain diseases but further study on their pharmacokinetics will be required in order to determine the optimal formulation, dosage and route of administration.
Article
Objectives There is overlap between the typical age of onset of bipolar disorder and the age of peak athletic success. Additionally, eating disorders are prevalent psychiatric disorders in athletes. Despite the relevance of both disorders in this population, there remains a need for treatment guidelines, especially when present as comorbidities given the complex interplay between them. Methods This report provides background information and utilizes a case report to explore the presentation and treatment of bipolar disorder comorbid with an eating disorder in an athlete. It specifically highlights the case of an elite female long distance runner utilizing a multidisciplinary approach specific to the patient’s unique needs as an athlete. Results Treatment of this elite athlete utilized strategic pharmacotherapy taking into consideration her training and competition cycles. At 16 week follow-up, the patient was psychiatrically stable, experienced improvement in her running and felt confident in choosing to stay on medication and continue her running career. Conclusion It is important for providers who work with high-level athletes to provide treatment choices that allow athletes to safely and successfully continue their sport while adequately treating their mental illness. Treatment guidelines that increasingly take into consideration complex psychiatric comorbidities and nuanced pharmacologic approaches are needed in order to advance the field of sports psychiatry.
ResearchGate has not been able to resolve any references for this publication.