Lithium (medication)

Last updated

Lithium
Lithium-carbonate2DCSD.svg
Lithium-carbonate-xtal-1979-Mercury-3D-sf.png
Lithium carbonate, an example of a lithium salt
Clinical data
Trade names Many [1]
AHFS/Drugs.com Monograph
MedlinePlus a681039
License data
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth, parenteral
Drug class Mood stabilizer
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Depends on formulation
Protein binding None
Metabolism Kidney
Elimination half-life 24 h, 36 h (elderly) [4]
Excretion >95% kidney
Identifiers
  • Lithium(1+)
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula Li+
Molar mass 6.94 g·mol−1
3D model (JSmol)
  • [Li+]
  • InChI=1S/Li/q+1
  • Key:HBBGRARXTFLTSG-UHFFFAOYSA-N

Certain lithium compounds, also known as lithium salts, are used as psychiatric medication, [4] primarily for bipolar disorder and for major depressive disorder. [4] Lithium is taken orally (by mouth). [4]

Contents

Common side effects include increased urination, shakiness of the hands, and increased thirst. [4] Serious side effects include hypothyroidism, diabetes insipidus, and lithium toxicity. [4] Blood level monitoring is recommended to decrease the risk of potential toxicity. [4] If levels become too high, diarrhea, vomiting, poor coordination, sleepiness, and ringing in the ears may occur. [4] Lithium is teratogenic and can cause birth defects at high doses, especially during the first trimester of pregnancy. The use of lithium while breastfeeding is controversial; however, many international health authorities advise against it, and the long-term outcomes of perinatal lithium exposure have not been studied. [5] The American Academy of Pediatrics lists lithium as contraindicated for pregnancy and lactation. [6] The United States Food and Drug Administration categorizes lithium as having positive evidence of risk for pregnancy and possible hazardous risk for lactation. [6] [7]

Lithium salts are classified as mood stabilizers. [4] Lithium's mechanism of action is not known. [4]

In the nineteenth century, lithium was used in people who had gout, epilepsy, and cancer. [8] Its use in the treatment of mental disorders began with Carl Lange in Denmark [9] and William Alexander Hammond in New York City, [10] who used lithium to treat mania from the 1870s onwards, based on now-discredited theories involving its effect on uric acid. Use of lithium for mental disorders was re-established (on a different theoretical basis) in 1948 by John Cade in Australia. [8] Lithium carbonate is on the World Health Organization's List of Essential Medicines, [11] and is available as a generic medication. [4] In 2020, it was the 197th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [12] [13] It appears to be underused in older people, [14] though the reason for that is unclear.

Medical uses

A bottle of lithium medicine containing 300 mg capsules of lithium carbonate. Lithium300mg.jpg
A bottle of lithium medicine containing 300 mg capsules of lithium carbonate.

In 1970, lithium was approved by the United States Food and Drug Administration (FDA) for the treatment of bipolar disorder, which remains its primary use in the United States. [4] [15] It is sometimes used when other treatments are not effective in a number of other conditions, including major depression, [16] schizophrenia, disorders of impulse control, and some psychiatric disorders in children. [4] Because the FDA has not approved lithium for the treatment of other disorders, such use is off-label. [17] [16]

Bipolar disorder

Lithium is primarily used as a maintenance drug in the treatment of bipolar disorder to stabilize mood and prevent manic episodes, but it may also be helpful in the acute treatment of manic episodes. [18] Although recommended by treatment guidelines for the treatment of depression in bipolar disorder, the evidence that lithium is superior to placebo for acute depression is low-quality; [19] [20] atypical antipsychotics are considered more effective for treating acute depressive episodes. [21] Lithium carbonate treatment was previously considered to be unsuitable for children; however, more recent studies show its effectiveness for treatment of early-onset bipolar disorder in children as young as eight. The required dosage is slightly less than the toxic level (representing a low therapeutic index), requiring close monitoring of blood levels of lithium carbonate during treatment. [22] Within the therapeutic range there is a dose response relationship. [23] A limited amount of evidence suggests lithium carbonate may contribute to treatment of substance use disorders for some people with bipolar disorder. [24] [25] [26] Although it is believed that lithium prevents suicide in people with bipolar disorder, a 2022 systematic review found that "Evidence from randomised trials is inconclusive and does not support the idea that lithium prevents suicide or suicidal behaviour." [27]

Schizophrenic disorders

Lithium is recommended for the treatment of schizophrenic disorders only after other antipsychotics have failed; it has limited effectiveness when used alone. [4] The results of different clinical studies of the efficacy of combining lithium with antipsychotic therapy for treating schizophrenic disorders have varied. [4]

Major depressive disorder

Lithium is widely prescribed as an adjunct treatment for depression. [17]

Augmentation

If therapy with antidepressants (such as selective serotonin reuptake inhibitors [SSRIs]) does not fully treat the symptoms of major depressive disorder (MDD) then a second augmentation agent is sometimes added to the therapy. [28] Lithium is one of the few augmentation agents for antidepressants to demonstrate efficacy in treating MDD in multiple randomized controlled trials and it has been prescribed (off-label) for this purpose since the 1980s. [16] A 2019 systematic review found some evidence of the clinical utility of adjunctive lithium, but the majority of supportive evidence is dated. [29]

Monotherapy

There are a few old studies indicating efficacy of lithium for acute depression with lithium having the same efficacy as tricyclic antidepressants. [30] A recent study concluded that lithium works best on chronic and recurrent depression when compared to modern antidepressant (i.e. citalopram) but not for patients with no history of depression. [31] A 2019 systemic review found no evidence to support the use of lithium for monotherapy. [29]

Prevention of suicide

Lithium is widely believed to prevent suicide, and often used in clinical practice towards that end. However, meta-analyses, faced with evidence-base limitations, have yielded differing results, and it therefore remains unclear whether or not lithium is efficacious in the prevention of suicide. [32] [33] [34] [35] [36] [37]

Alzheimer's disease

Alzheimer's disease affects forty-five million people and is the fifth leading cause of death in the 65 plus population. [38] [ failed verification ] There is no complete cure for the disease, currently. However, lithium is being evaluated for its effectiveness as a potential therapeutic measure. One of the leading causes of Alzheimer's is the hyperphosphorylation of the tau protein by the enzyme GSK-3, which leads to the overproduction of amyloid peptides that cause cell death. [38] To combat this toxic amyloid aggregation, lithium upregulates the production of neuroprotectors and neurotrophic factors, as well as inhibiting the GSK-3 enzyme. [39] Lithium also stimulates neurogenesis within the hippocampus, making it thicker. [39] Yet another cause of Alzheimer's disease is the dysregulation of calcium ions within the brain. [40] Too much or too little calcium within the brain can lead to cell death. [40] Lithium is able to restore the intracellular calcium homeostasis through inhibiting the wrongful influx of calcium upstream. [40] It also promotes the redirection of the influx of the calcium ions into the lumen of the endoplasmic reticulum of the cells to reduce the oxidative stress within the mitochondria. [40]

In 2009, a study was performed by Hampel and colleagues [41] that asked patients with Alzheimer's to take a low dose of lithium daily for three months; it resulted in a significant slowing of cognitive decline, benefitting patients being in the prodromal stage the most. [39] Upon a secondary analysis, the brains of the Alzheimer's patients were studied and shown to have an increase in BDNF markers, meaning they had actually shown cognitive improvement. [39] Another study, a population study this time by Kessing et al., [42] showed a negative correlation between Alzheimer's disease deaths and the presence of lithium in drinking water. [39] Areas with increased lithium in their drinking water showed less dementia overall in their population. [39]

Monitoring

Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities, as it interferes with the regulation of sodium and water levels in the body, and can cause dehydration. Dehydration, which is compounded by heat, can result in increasing lithium levels. The dehydration is due to lithium inhibition of the action of antidiuretic hormone, which normally enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine, leading to consequent loss of body water and thirst. [43]

Lithium concentrations in whole blood, plasma, serum or urine may be measured using instrumental techniques as a guide to therapy, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Serum lithium concentrations are usually in the range of 0.5–1.3  mmol/L (0.5–1.3  mEq/L) in well-controlled people, but may increase to 1.8–2.5 mmol/L in those who accumulate the drug over time and to 3–10 mmol/L in acute overdose. [44] [45]

Lithium salts have a narrow therapeutic/toxic ratio, so should not be prescribed unless facilities for monitoring plasma concentrations are available. Doses are adjusted to achieve plasma concentrations of 0.4 [lower-alpha 1] [lower-alpha 2] to 1.2 mmol/L [46] on samples taken 12 hours after the preceding dose.

Given the rates of thyroid dysfunction, thyroid parameters should be checked before lithium is instituted and monitored after 3–6 months and then every 6–12 months. [47]

Given the risks of kidney malfunction, serum creatinine and eGFR should be checked before lithium is instituted and monitored after 3–6 months at regular interval. Patients who have a rise in creatinine on three or more occasions, even if their eGFR is > 60 ml/min/ 1.73m2 require further evaluation, including a urinalysis for haematuria, proteinuria, a review of their medical history with attention paid to cardiovascular, urological and medication history, and blood pressure control and management. Overt proteinuria should be further quantified with a urine protein to creatinine ratio. [48]

Discontinuation

For patients who have achieved long term remission, it is recommended to discontinue lithium gradually and in a controlled fashion. [49] [30]

Discontinuation symptoms may occur in patients stopping the medication including irritability, restlessness and somatic symptoms like vertigo, dizziness or lightheadedness. Symptoms occur within the first week and are generally mild and self-limiting within weeks. [50]

Cluster headaches, migraine and hypnic headache

Studies testing prophylactic use of lithium in cluster headaches (when compared to verapamil), migraine attacks and hypnic headache indicate good efficacy. [30]

Adverse effects

The adverse effects of lithium include: [51] [52] [53] [54] [55] [56] [57]

Very Common (> 10% incidence) adverse effects
Common (1–10%) adverse effects
Unknown incidence

Lithium carbonate can induce a 1–2 kg of weight gain. [62]

In addition to tremors, lithium treatment appears to be a risk factor for development of parkinsonism-like symptoms, although the causal mechanism remains unknown. [63]

Most side effects of lithium are dose-dependent. The lowest effective dose is used to limit the risk of side effects.

Hypothyroidism

The rate of hypothyroidism is around six times higher in people who take lithium. Low thyroid hormone levels in turn increase the likelihood of developing depression. People taking lithium thus should routinely be assessed for hypothyroidism and treated with synthetic thyroxine if necessary. [62]

Because lithium competes with the antidiuretic hormone in the kidney, it increases water output into the urine, a condition called nephrogenic diabetes insipidus. Clearance of lithium by the kidneys is usually successful with certain diuretic medications, including amiloride and triamterene. [64] It increases the appetite and thirst ("polydypsia") and reduces the activity of thyroid hormone (hypothyroidism). [65] [66] The latter can be corrected by treatment with thyroxine and does not require the lithium dose to be adjusted. Lithium is also believed to cause renal dysfunction, although this does not appear to be common. [67]

Lambert et al. (2016), comparing the rate of hypothyroidism in patients with bipolar disorder treated with 9 different medications, found that lithium users do not have a particularly high rate of hypothyroidism (8.8%) among BD patients – only 1.39 times the rate in oxcarbazepine users (6.3%). Lithium and quetiapine are not statistically different in terms of hypothyroidism rates. However, lithium users are tested much more frequently for hypothyroidism than those using other drugs. The authors write that there may be an element of surveillance bias in understanding lithium's effects on the thyroid glands, as lithium users are tested 2.3–3.1 times as often. Furthermore, the authors argue that because hypothyrodism is common among BD patients regardless of lithium treatment, regular thyroid testing should be applied to all BD patients, not just those on lithium. [68] [60]

Pregnancy and breast feeding

Lithium is a teratogen, causing birth defects in a small number of newborn babies. [69] Case reports and several retrospective studies have demonstrated possible increases in the rate of a congenital heart defect known as Ebstein's anomaly, if taken during a woman's pregnancy. [70] As a consequence, fetal echocardiography is routinely performed in pregnant women taking lithium to exclude the possibility of cardiac anomalies. Lamotrigine seems to be a possible alternative to lithium in pregnant women for the treatment of acute bipolar depression or for the management of bipolar patients with normal mood. [71] Gabapentin [72] and clonazepam [73] are also indicated as antipanic medications during the childbearing years and during pregnancy. Valproic acid and carbamazepine also tend to be associated with teratogenicity.

While it appears to be safe to use while breastfeeding a number of guidelines list it as a contraindication [74] including the British National Formulary. [75]

Kidney damage

Lithium has been associated with several forms of kidney injury. [76] [77] It is estimated that impaired urinary concentrating ability is present in at least half of individuals on chronic lithium therapy, a condition called lithium-induced nephrogenic diabetes insipidus. [77] Continued use of lithium can lead to more serious kidney damage in an aggravated form of diabetes insipidus. [78] [79] In rare cases, some forms of lithium-caused kidney damage may be progressive and lead to end-stage kidney failure with a reported incidence of 0.2% to 0.7%. [80]

Some reports of kidney damage may be wrongly attributed to lithium, increasing the apparent rate of this adverse effect. [59] Nielsen et al. (2018), citing 6 large observational studies since 2010, argues that findings of decreased kidney function are partially inflated by surveillance bias. Furthermore, modern data does not show that lithium increases the risk of end-stage kidney disease. [60] Davis et al. (2018), using literature from a wider timespan (1977–2018), also found that lithium's association with chronic kidney disease is unproven with various contradicting results. They also find contradicting results regarding end-stage kidney disease. [81]

A 2015 nationwide study suggests that chronic kidney disease can be avoided by maintaining the serum lithium concentration at a level of 0.6–0.8 mmol/L and by monitoring serum creatinine every 3–6 months. [60]

Hyperparathyroidism

Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia.

Interactions

Lithium plasma concentrations are known to be increased with concurrent use of diuretics—especially loop diuretics (such as furosemide) and thiazides—and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. [51] Lithium concentrations can also be increased with concurrent use of ACE inhibitors such as captopril, enalapril, and lisinopril. [82]

Lithium is primarily cleared from the body through glomerular filtration, but some is then reabsorbed together with sodium through the proximal tubule. Its levels are therefore sensitive to water and electrolyte balance. [83] Diuretics act by lowering water and sodium levels; this causes more reabsorption of lithium in the proximal tubules so that the removal of lithium from the body is less, leading to increased blood levels of lithium. [83] [84] ACE inhibitors have also been shown in a retrospective case-control study to increase lithium concentrations. This is likely due to constriction of the afferent arteriole of the glomerulus, resulting in decreased glomerular filtration rate and clearance. Another possible mechanism is that ACE inhibitors can lead to a decrease in sodium and water. This will increase lithium reabsorption and its concentrations in the body. [83]

There are also drugs that can increase the clearance of lithium from the body, which can result in decreased lithium levels in the blood. These drugs include theophylline, caffeine, and acetazolamide. Additionally, increasing dietary sodium intake may also reduce lithium levels by prompting the kidneys to excrete more lithium. [85]

Lithium is known to be a potential precipitant of serotonin syndrome in people concurrently on serotonergic medications such as antidepressants, buspirone and certain opioids such as pethidine (meperidine), tramadol, oxycodone, fentanyl and others. [51] [86] Lithium co-treatment is also a risk factor for neuroleptic malignant syndrome in people on antipsychotics and other antidopaminergic medications. [87]

High doses of haloperidol, fluphenazine, or flupenthixol may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported. [88] Indeed, these and other antipsychotics have been associated with increased risk of lithium neurotoxicity, even with low therapeutic lithium doses. [89] [90]

Classical psychedelics such as psilocybin and LSD may cause seizures if taken while using lithium, although further research is needed. [91]

Overdose

Lithium toxicity, which is also called lithium overdose and lithium poisoning, is the condition of having too much lithium in the blood. This condition also happens in persons that are taking lithium in which the lithium levels are affected by drug interactions in the body.

In acute toxicity, people have primarily gastrointestinal symptoms such as vomiting and diarrhea, which may result in volume depletion. During acute toxicity, lithium distributes later into the central nervous system resulting in mild neurological symptoms, such as dizziness. [47]

In chronic toxicity, people have primarily neurological symptoms which include nystagmus, tremor, hyperreflexia, ataxia, and change in mental status. During chronic toxicity, the gastrointestinal symptoms seen in acute toxicity are less prominent. The symptoms are often vague and nonspecific. [92]

If the lithium toxicity is mild or moderate, lithium dosage is reduced or stopped entirely. If the toxicity is severe, lithium may need to be removed from the body.

Mechanism of action

The specific biochemical mechanism of lithium action in stabilizing mood is unknown. [4]

Upon ingestion, lithium becomes widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing norepinephrine release and increasing serotonin synthesis. [93]

Unlike many other psychoactive drugs, Li+
 typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations. [93] Lithium may also increase the release of serotonin by neurons in the brain. [94] In vitro studies performed on serotonergic neurons from rat raphe nuclei have shown that when these neurons are treated with lithium, serotonin release is enhanced during a depolarization compared to no lithium treatment and the same depolarization. [95]

Lithium both directly and indirectly inhibits GSK3β (glycogen synthase kinase 3β) which results in the activation of mTOR. This leads to an increase in neuroprotective mechanisms by facilitating the Akt signaling pathway. [96] GSK-3β is a downstream target of monoamine systems. As such, it is directly implicated in cognition and mood regulation. [97] [96] During mania, GSK-3β is activated via dopamine overactivity. [96] GSK-3β inhibits the transcription factors β-catenin and cyclic AMP (cAMP) response element binding protein (CREB), by phosphorylation. This results in a decrease in the transcription of important genes encoding for neurotrophins. [98] [99] [100] In addition, several authors proposed that pAp-phosphatase could be one of the therapeutic targets of lithium. [101] [102] This hypothesis was supported by the low Ki of lithium for human pAp-phosphatase compatible within the range of therapeutic concentrations of lithium in the plasma of people (0.8–1 mM). The Ki of human pAp-phosphatase is ten times lower than that of GSK3β (glycogen synthase kinase 3β). Inhibition of pAp-phosphatase by lithium leads to increased levels of pAp (3′-5′ phosphoadenosine phosphate), which was shown to inhibit PARP-1. [103]

Another mechanism proposed in 2007 is that lithium may interact with nitric oxide (NO) signalling pathway in the central nervous system, which plays a crucial role in neural plasticity. The NO system could be involved in the antidepressant effect of lithium in the Porsolt forced swimming test in mice. [104] [105] It was also reported that NMDA receptor blockage augments antidepressant-like effects of lithium in the mouse forced swimming test, [106] indicating the possible involvement of NMDA receptor/NO signaling in the action of lithium in this animal model of learned helplessness.

Lithium possesses neuroprotective properties by preventing apoptosis and increasing cell longevity. [107]

Although the search for a novel lithium-specific receptor is ongoing, the high concentration of lithium compounds required to elicit a significant pharmacological effect leads mainstream researchers to believe that the existence of such a receptor is unlikely. [108]

Oxidative metabolism

Evidence suggests that mitochondrial dysfunction is present in patients with bipolar disorder. [107] Oxidative stress and reduced levels of anti-oxidants (such as glutathione) lead to cell death. Lithium may protect against oxidative stress by up-regulating complex I and II of the mitochondrial electron transport chain. [107]

Dopamine and G-protein coupling

During mania, there is an increase in neurotransmission of dopamine that causes a secondary homeostatic down-regulation, resulting in decreased neurotransmission of dopamine, which can cause depression. [107] Additionally, the post-synaptic actions of dopamine are mediated through G-protein coupled receptors. Once dopamine is coupled to the G-protein receptors, it stimulates other secondary messenger systems that modulate neurotransmission. Studies found that in autopsies (which do not necessarily reflect living people), people with bipolar disorder had increased G-protein coupling compared to people without bipolar disorder. [107] Lithium treatment alters the function of certain subunits of the dopamine associated G-protein, which may be part of its mechanism of action. [107]

Glutamate and NMDA receptors

Glutamate levels are observed to be elevated during mania. Lithium is thought to provide long-term mood stabilization and have anti-manic properties by modulating glutamate levels. [107] It is proposed that lithium competes with magnesium for binding to NMDA glutamate receptor, increasing the availability of glutamate in post-synaptic neurons, leading to a homeostatic increase in glutamate re-uptake which reduces glutamatergic transmission. [107] The NMDA receptor is also affected by other neurotransmitters such as serotonin and dopamine. Effects observed appear exclusive to lithium and have not been observed by other monovalent ions such as rubidium and caesium. [107]

GABA receptors

GABA is an inhibitory neurotransmitter that plays an important role in regulating dopamine and glutamate neurotransmission. [107] It was found that patients with bipolar disorder had lower GABA levels, which results in excitotoxicity and can cause apoptosis (cell loss). Lithium has been shown to increase the level of GABA in plasma and cerebral spinal fluid. [109] Lithium counteracts these degrading processes by decreasing pro-apoptotic proteins and stimulating release of neuroprotective proteins. [107] Lithium's regulation of both excitatory dopaminergic and glutamatergic systems through GABA may play a role in its mood stabilizing effects. [110]

Cyclic AMP secondary messengers

Lithium's therapeutic effects are thought to be partially attributable to its interactions with several signal transduction mechanisms. [111] The cyclic AMP secondary messenger system is shown to be modulated by lithium. Lithium was found to increase the basal levels of cyclic AMP but impair receptor coupled stimulation of cyclic AMP production. [107] It is hypothesized that the dual effects of lithium are due to the inhibition of G-proteins that mediate cyclic AMP production. [107] Over a long period of lithium treatment, cyclic AMP and adenylate cyclase levels are further changed by gene transcription factors. [107]

Inositol depletion hypothesis

Lithium treatment has been found to inhibit the enzyme inositol monophosphatase, involved in degrading inositol monophosphate to inositol required in PIP2 synthesis. This leads to lower levels of inositol triphosphate, created by decomposition of PIP2. [112] This effect has been suggested to be further enhanced with an inositol triphosphate reuptake inhibitor. Inositol disruptions have been linked to memory impairment and depression. It is known with good certainty that signals from the receptors coupled to the phosphoinositide signal transduction are affected by lithium. [113] myo-inositol is also regulated by the high affinity sodium mI transport system (SMIT). Lithium is hypothesized to inhibit mI entering the cells and mitigating the function of SMIT. [107] Reductions of cellular levels of myo-inositol results in the inhibition of the phosphoinositide cycle. [107]

Neurotrophic Factors

Various neurotrophic factors such as BDNF and mesencephalic astrocyte-derived neurotrophic factor have been shown to be modulated by various mood stabilizers. [114]

History

Lithium was first used in the 19th century as a treatment for gout after scientists discovered that, at least in the laboratory, lithium could dissolve uric acid crystals isolated from the kidneys. The levels of lithium needed to dissolve urate in the body, however, were toxic. [115] Because of prevalent theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark [9] and William Alexander Hammond in New York City [10] used lithium to treat mania from the 1870s onwards.

By the turn of the 20th century, as theory regarding mood disorders evolved and so-called "brain gout" disappeared as a medical entity, the use of lithium in psychiatry was largely abandoned; however, a number of lithium preparations were still produced for the control of renal calculi and uric acid diathesis. [17] As accumulating knowledge indicated a role for excess sodium intake in hypertension and heart disease, lithium salts were prescribed to patients for use as a replacement for dietary table salt (sodium chloride). This practice and the sale of lithium itself were both banned in the United States in February 1949, following publication of reports detailing side effects and deaths. [116]

Also in 1949, the Australian psychiatrist John Cade and Australian biochemist Shirley Andrews rediscovered the usefulness of lithium salts in treating mania while working at the Royal Park Psychiatric Hospital in Victoria. [117] They were injecting rodents with urine extracts taken from manic patients in an attempt to isolate a metabolic compound which might be causing mental symptoms. Since uric acid in gout was known to be psychoactive, (adenosine receptors on neurons are stimulated by it; caffeine blocks them), they needed soluble urate for a control. They used lithium urate, already known to be the most soluble urate compound, and observed that it caused the rodents to become tranquil. Cade and Andrews traced the effect to the lithium ion itself, and after Cade ingested lithium himself to ensure its safety in humans, he proposed lithium salts as tranquilizers. He soon succeeded in controlling mania in chronically hospitalized patients with them. This was one of the first successful applications of a drug to treat mental illness, and it opened the door for the development of medicines for other mental problems in the next decades. [118]

The rest of the world was slow to adopt this treatment, largely because of deaths which resulted from even relatively minor overdosing, including those reported from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmark's Mogens Schou and Paul Baastrup in Europe, [115] and Samuel Gershon and Baron Shopsin in the U.S., this resistance was slowly overcome. Following the recommendation of the APA Lithium Task Force (William Bunney, Irvin Cohen (Chair), Jonathan Cole, Ronald R. Fieve, Samuel Gershon, Robert Prien, and Joseph Tupin [119] ), the application of lithium in manic illness was approved by the United States Food and Drug Administration in 1970, [120] becoming the 50th nation to do so. [17] In 1974, this application was extended to its use as a preventive agent for manic-depressive illness.

Fieve, who had opened the first lithium clinic in North America in 1966, helped popularize the psychiatric use of lithium through his national TV appearances and his bestselling book, Moodswing. In addition, Fieve and David L. Dunner developed the concept of "rapid cycling" bipolar disorder based on non-response to lithium.

Lithium has now become a part of Western popular culture. Characters in Pi , Premonition , Stardust Memories , American Psycho , Garden State , and An Unmarried Woman all take lithium. It's the chief constituent of the calming drug in Ira Levin's dystopian This Perfect Day. Sirius XM Satellite Radio in North America has a 1990s alternative rock station called Lithium, and several songs refer to the use of lithium as a mood stabilizer. These include: "Equilibrium met Lithium" by South African artist Koos Kombuis, "Lithium" by Evanescence, "Lithium" by Nirvana, "Lithium and a Lover" by Sirenia, "Lithium Sunset", from the album Mercury Falling by Sting, [121] and "Lithium" by Thin White Rope.

7 Up

As with cocaine in Coca-Cola, lithium was widely marketed as one of a number of patent medicine products popular in the late-19th and early-20th centuries, and was the medicinal ingredient of a refreshment beverage. Charles Leiper Grigg, who launched his St. Louis-based company The Howdy Corporation, invented a formula for a lemon-lime soft drink in 1920. The product, originally named "Bib-Label Lithiated Lemon-Lime Soda", was launched two weeks before the Wall Street Crash of 1929. [122] It contained the mood stabilizer lithium citrate, and was one of a number of patent medicine products popular in the late-19th and early-20th centuries. [123] Its name was soon changed to 7 Up. All American beverage makers were forced to remove lithium from beverages in 1948. Despite the ban, in 1950, the Painesville Telegraph still carried an advertisement for a lithiated lemon beverage. [124]

Salts and product names

Lithium carbonate (Li
2CO
3) is the most commonly used form of lithium salts, a carbonic acid involving the lithium element and a carbonate ion. Other lithium salts are also used as medication, such as lithium citrate (Li
3C
6H
5O
7), lithium sulfate, lithium chloride, and lithium orotate. [125] [126] Nanoparticles and microemulsions have also been invented as drug delivery mechanisms. As of 2020, there is a lack of evidence that alternate formulations or salts of lithium would reduce the need for monitoring serum lithium levels or to lower systemic toxicity. [125]

As of 2017 lithium was marketed under many brand names worldwide, including Cade, Calith, Camcolit, Carbolim, Carbolit, Carbolith, Carbolithium, Carbolitium, Carbonato de Litio, Carboron, Ceglution, Contemnol, Efadermin (Lithium and Zinc Sulfate), Efalith (Lithium and Zinc Sulfate), Elcab, Eskalit, Eskalith, Frimania, Hypnorex, Kalitium, Karlit, Lalithium, Li-Liquid, Licarb, Licarbium, Lidin, Ligilin, Lilipin, Lilitin, Limas, Limed, Liskonum, Litarex, Lithane, Litheum, Lithicarb, Lithii carbonas, Lithii citras, Lithioderm, Lithiofor, Lithionit, Lithium, Lithium aceticum, Lithium asparagicum, Lithium Carbonate, Lithium Carbonicum, Lithium Citrate, Lithium DL-asparaginat-1-Wasser, Lithium gluconicum, Lithium-D-gluconat, Lithiumcarbonaat, Lithiumcarbonat, Lithiumcitrat, Lithiun, Lithobid, Lithocent, Lithotabs, Lithuril, Litiam, Liticarb, Litijum, Litio, Litiomal, Lito, Litocarb, Litocip, Maniprex, Milithin, Neurolepsin, Plenur, Priadel, Prianil, Prolix, Psicolit, Quilonium, Quilonorm, Quilonum, Téralithe, and Theralite. [1]

Research

Tentative evidence in Alzheimer's disease showed that lithium may slow progression. [127] [128] It has been studied for its potential use in the treatment of amyotrophic lateral sclerosis (ALS), but a study showed lithium had no effect on ALS outcomes. [129]

See also

Notes

  1. ↑ The UK Electronic Medical Compendium recommends 0.4–0.8  mmol/L plasma lithium level in adults for prophylaxis of recurrent affective bipolar manic-depressive illness Camcolit 250 mg Lithium Carbonate Archived 4 March 2016 at the Wayback Machine Revision 2 December 2010, Retrieved 5 May 2011
  2. ↑ One study (Solomon DA, Ristow WR, Keller MB, Kane JM, Gelenberg AJ, Rosenbaum JF, et al. (October 1996). "Serum lithium levels and psychosocial function in patients with bipolar I disorder". The American Journal of Psychiatry. 153 (10): 1301–1307. doi:10.1176/ajp.153.10.1301. PMID   8831438.) concluded a "low" dose of 0.4–0.6 mmol/L serum lithium treatment for patients with bipolar 1 disorder had less side effects, but a higher rate of relapse, than a "standard" dose of 0.8–1.0 mmol/L. However, a reanalysis of the same experimental data (Perlis RH, Sachs GS, Lafer B, Otto MW, Faraone SV, Kane JM, et al. (July 2002). "Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data". The American Journal of Psychiatry. 159 (7): 1155–1159. doi:10.1176/appi.ajp.159.7.1155. PMID   12091193.) concluded the higher rate of relapse for the "low" dose was due to abrupt changes in the lithium serum levels[ improper synthesis? ]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Bipolar disorder</span> Mental disorder that causes periods of depression and abnormally elevated mood

Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually also a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others. The risk of suicide is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30–40% engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder.

Bipolar I disorder is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other times, have one or more depressive episodes. Typically, these manic episodes can last at least 7 days for most of each day to the extent that the individual may need medical attention, while the depressive episodes last at least 2 weeks.

<span class="mw-page-title-main">Mood stabilizer</span> Psychiatric medication used to treat mood disorders

A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder.

<span class="mw-page-title-main">Clozapine</span> Atypical antipsychotic medication

Clozapine is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease.

A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also commonly used 'off-label' for treatment of chemotherapy induced nausea and vomiting (CINV) and as an appetite stimulant. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Lamotrigine</span> Medication used for bipolar disorder, epilepsy, & many seizure disorders

Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression in any groups except for the severely depressed; but for patients with bipolar disorder who are not currently symptomatic, it appears to reduce the risk of future episodes of depression.

<span class="mw-page-title-main">Venlafaxine</span> Antidepressant medication

Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. Studies have shown that venlafaxine improves post-traumatic stress disorder (PTSD). It may also be used for chronic pain. It is taken orally. It is also available as the salt venlafaxine besylate in an extended-release formulation.

<span class="mw-page-title-main">Lithium orotate</span> Chemical compound

Lithium orotate (C5H3LiN2O4) is a salt of orotic acid and lithium. It is available as the monohydrate, LiC5H3N2O4·H2O. In this compound, lithium is non-covalently bound to an orotate ion, rather than to a carbonate or other ion, and like other salts, dissolves in solution to produce free lithium ions. It is marketed as a dietary supplement, though it has been researched minimally between 1973–1986 to treat certain medical conditions, such as alcoholism and Alzheimer's disease.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

Biological psychiatry or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics, epigenetics and physiology to investigate the biological bases of behavior and psychopathology. Biopsychiatry is the branch of medicine which deals with the study of the biological function of the nervous system in mental disorders.

The emphasis of the treatment of bipolar disorder is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms. Treatment methods include pharmacological and psychological techniques.

Cyclical variations in moods and energy levels have been recorded at least as far back as several thousand years. The words "melancholia" and "mania" have their etymologies in Ancient Greek. The word melancholia is derived from melas/μελας, meaning "black", and chole/χολη, meaning "bile" or "gall", indicative of the term's origins in pre-Hippocratic humoral theories. A man known as Aretaeus of Cappadocia has the first records of analyzing the symptoms of depression and mania in the 1st century of Greece. There is documentation that explains how bath salts were used to calm those with manic symptoms and also help those who are dealing with depression. Even today, lithium is used as a treatment to bipolar disorder which is significant because lithium could have been an ingredient in the Greek bath salt. Centuries passed and very little was studied or discovered. It wasn't until the mid-19th century that a French psychiatrist by the name of Jean-Pierre Falret wrote an article describing "circular insanity" and this is believed to be the first recorded diagnosis of bipolar disorder. Years later, in the early 1900s, Emil Kraepelin, a German psychiatrist, analyzed the influence of biology on mental disorders, including bipolar disorder. His studies are still used as the basis of classification of mental disorders today.

Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder (BP-I).

<span class="mw-page-title-main">Inositol-phosphate phosphatase</span> Class of enzymes

The enzyme Inositol phosphate-phosphatase is of the phosphodiesterase family of enzymes. It is involved in the phosphophatidylinositol signaling pathway, which affects a wide array of cell functions, including but not limited to, cell growth, apoptosis, secretion, and information processing. Inhibition of inositol monophosphatase may be key in the action of lithium in treating bipolar disorder, specifically manic depression.

<span class="mw-page-title-main">Lurasidone</span> Atypical antipsychotic medication

Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.

<span class="mw-page-title-main">Lithium toxicity</span> Medical condition

Lithium toxicity, also known as lithium overdose, is the condition of having too much lithium. Symptoms may include a tremor, increased reflexes, trouble walking, kidney problems, and an altered level of consciousness. Some symptoms may last for a year after levels return to normal. Complications may include serotonin syndrome.

Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.

Irvin M. Cohen, M.D. (1922–2019) was a psychiatrist specializing in psychopharmacology, recognized for his role in the early use of chlorpromazine in the treatment of schizophrenia, the development of the first benzodiazepine (Librium) treatments in depressive patients, and in the adoption of lithium to treat bipolar disorder.

References

  1. 1 2 "Lithium brands". Drugs.com. Archived from the original on 5 April 2017. Retrieved 4 April 2017.
  2. ↑ Anvisa (31 March 2023). "RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  3. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 "Lithium Salts". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 1 December 2015.
  5. ↑ Poels EM, Bijma HH, Galbally M, Bergink V (December 2018). "Lithium during pregnancy and after delivery: a review". International Journal of Bipolar Disorders. 6 (1): 26. doi: 10.1186/s40345-018-0135-7 . PMC   6274637 . PMID   30506447.
  6. 1 2 Armstrong C (15 September 2008). "ACOG Guidelines on Psychiatric Medication Use During Pregnancy and Lactation". American Family Physician. 78 (6): 772. ISSN   0002-838X. Archived from the original on 27 January 2022. Retrieved 27 January 2022.
  7. ↑ "Lithium Carbonate Medication Guide" (PDF). U.S. FDA. Archived (PDF) from the original on 27 January 2022. Retrieved 27 January 2022.
  8. 1 2 Sneader W (2005). Drug discovery : a history (Rev. and updated ed.). Chichester: Wiley. p. 63. ISBN   978-0-471-89979-2. Archived from the original on 8 September 2017.
  9. 1 2 Lenox RH, Watson DG (February 1994). "Lithium and the brain: a psychopharmacological strategy to a molecular basis for manic depressive illness". Clinical Chemistry. 40 (2): 309–314. doi: 10.1093/clinchem/40.2.309 . PMID   8313612.
  10. 1 2 Mitchell PB, Hadzi-Pavlovic D (2000). "Lithium treatment for bipolar disorder" (PDF). Bulletin of the World Health Organization. 78 (4): 515–517. PMC   2560742 . PMID   10885179. Archived from the original (PDF) on 1 April 2012.
  11. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  12. ↑ "The Top 300 of 2020". ClinCalc. Archived from the original on 26 March 2023. Retrieved 7 October 2022.
  13. ↑ "Lithium – Drug Usage Statistics". ClinCalc. Archived from the original on 10 June 2023. Retrieved 7 October 2022.
  14. ↑ Almeida OP, Etherton-Beer C, Kelty E, Sanfilippo F, Preen DB, Page A (27 March 2023). "Lithium dispensed for adults aged ≥ 50 years between 2012 and 2021: Analyses of a 10% sample of the Australian Pharmaceutical Benefits Scheme". The American Journal of Geriatric Psychiatry. 31 (9): 716–725. doi:10.1016/j.jagp.2023.03.012. ISSN   1064-7481. PMID   37080815. S2CID   257824414. Archived from the original on 31 March 2023. Retrieved 31 March 2023.
  15. ↑ Fieve RR (1984). "Lithium: its clinical uses and biological mechanisms of action". In Habig RL (ed.). The Brain, Biochemistry, and Behavior: Proceedings of the Sixth Arnold O. Beckman Conference in Clinical Chemistry. American Association for Clinical Chemistry. p. 170. ISBN   978-0-915274-22-2. Archived from the original on 26 February 2024. Retrieved 27 May 2022.
  16. 1 2 3 Bauer M, Adli M, Ricken R, Severus E, Pilhatsch M (April 2014). "Role of lithium augmentation in the management of major depressive disorder". CNS Drugs. 28 (4): 331–342. doi:10.1007/s40263-014-0152-8. PMID   24590663. S2CID   256840.
  17. 1 2 3 4 Shorter E (June 2009). "The history of lithium therapy". Bipolar Disorders. 11 (Suppl 2): 4–9. doi:10.1111/j.1399-5618.2009.00706.x. PMC   3712976 . PMID   19538681.
  18. ↑ McKnight RF, de La Motte de Broöns de Vauvert SJ, Chesney E, Amit BH, Geddes J, Cipriani A (June 2019). "Lithium for acute mania". The Cochrane Database of Systematic Reviews. 2019 (6): CD004048. doi:10.1002/14651858.CD004048.pub4. PMC   6544558 . PMID   31152444.
  19. ↑ Rakofsky JJ, Lucido MJ, Dunlop BW (July 2022). "Lithium in the treatment of acute bipolar depression: A systematic review and meta-analysis". Journal of Affective Disorders. 308: 268–280. doi:10.1016/j.jad.2022.04.058. PMID   35429528. S2CID   248161621.
  20. ↑ Riedinger MA, van der Wee NJ, Giltay EJ, de Leeuw M (September 2023). "Lithium in bipolar depression: A review of the evidence". Human Psychopharmacology. 38 (5): e2881. doi: 10.1002/hup.2881 . hdl: 10067/2003410151162165141 . PMID   37789577.
  21. ↑ Cai L, Chen G, Yang H, Bai Y (July 2023). "Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression: a systematic review". International Clinical Psychopharmacology. 38 (4): 249–260. doi:10.1097/YIC.0000000000000449. PMID   36947416. S2CID   257665886.
  22. ↑ Semple, David "Oxford Hand Book of Psychiatry" Oxford Press. 2005.[ page needed ]
  23. ↑ Hsu CW, Tsai SY, Tseng PT, Liang CS, Vieta E, Carvalho AF, et al. (May 2022). "Differences in the prophylactic effect of serum lithium levels on depression and mania in bipolar disorder: A dose-response meta-analysis". European Neuropsychopharmacology. 58: 20–29. doi:10.1016/j.euroneuro.2022.01.112. PMID   35158229. S2CID   246754349.
  24. ↑ Rosenberg JM, Salzman C (November 2007). "Update: new uses for lithium and anticonvulsants". CNS Spectrums. 12 (11): 831–841. doi:10.1017/S1092852900015571. PMID   17984856. S2CID   26227696.
  25. ↑ Frye MA, Salloum IM (December 2006). "Bipolar disorder and comorbid alcoholism: prevalence rate and treatment considerations". Bipolar Disorders. 8 (6): 677–685. doi:10.1111/j.1399-5618.2006.00370.x. PMID   17156154.
  26. ↑ Vornik LA, Brown ES (2006). "Management of comorbid bipolar disorder and substance abuse". The Journal of Clinical Psychiatry. 67 (Suppl 7): 24–30. PMID   16961421.
  27. ↑ Nabi Z, Stansfeld J, Plöderl M, Wood L, Moncrieff J (September 2022). "Effects of lithium on suicide and suicidal behaviour: a systematic review and meta-analysis of randomised trials". Epidemiology and Psychiatric Sciences. 31: e65. doi: 10.1017/S204579602200049X . PMC   9533115 . PMID   36111461.
  28. ↑ Ercis M, Ozerdem A, Singh B (March 2023). "When and How to Use Lithium Augmentation for Treating Major Depressive Disorder". The Journal of Clinical Psychiatry. 84 (2). doi:10.4088/jcp.23ac14813. PMID   36883886.
  29. 1 2 Undurraga J, Sim K, Tondo L, Gorodischer A, Azua E, Tay KH, et al. (February 2019). "Lithium treatment for unipolar major depressive disorder: Systematic review". Journal of Psychopharmacology. 33 (2): 167–176. doi:10.1177/0269881118822161. PMID   30698058. S2CID   59411183. Archived from the original on 20 February 2024. Retrieved 20 February 2024.
  30. 1 2 3 Bauer M, Grof P, Muller-Oerlinghausen B (2006). Lithium in Neuropsychiatry: The Comprehensive Guide. Taylor & Francis. ISBN   978-1-84184-515-9 . Retrieved 17 July 2021.
  31. ↑ Bauer M, Gitlin M (2016). "Treatment of Depression with Lithium". The Essential Guide to Lithium Treatment. Cham: Springer International Publishing. pp. 71–80. doi:10.1007/978-3-319-31214-9_7. ISBN   978-3-319-31212-5.
  32. ↑ Nabi Z, Stansfeld J, Plöderl M, Wood L, Moncrieff J (September 2022). "Effects of lithium on suicide and suicidal behaviour: a systematic review and meta-analysis of randomised trials". Epidemiology and Psychiatric Sciences. 31: e65. doi:10.1017/S204579602200049X. PMC   9533115 . PMID   36111461.
  33. ↑ Del Matto L, Muscas M, Murru A, Verdolini N, Anmella G, Fico G, et al. (September 2020). "Lithium and suicide prevention in mood disorders and in the general population: A systematic review". Neuroscience and Biobehavioral Reviews. 116: 142–153. doi:10.1016/j.neubiorev.2020.06.017. PMID   32561344. S2CID   219942979.
  34. ↑ Börjesson J, Gøtzsche PC (September 2019). "Effect of lithium on suicide and mortality in mood disorders: a systematic review". The International Journal of Risk & Safety in Medicine. 30 (3): 155–166. doi:10.3233/JRS-190058. PMID   31381531. S2CID   199451710.
  35. ↑ Riblet NV, Shiner B, Young-Xu Y, Watts BV (November 2022). "Lithium in the prevention of suicide in adults: systematic review and meta-analysis of clinical trials". BJPsych Open. 8 (6): e199. doi:10.1192/bjo.2022.605. PMC   9707499 . PMID   36384820.
  36. ↑ Cipriani A, Hawton K, Stockton S, Geddes JR (June 2013). "Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis". BMJ. 346: f3646. doi: 10.1136/bmj.f3646 . PMID   23814104.
  37. ↑ Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J (October 2006). "Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review". Bipolar Disorders. 8 (5p2): 625–639. doi: 10.1111/j.1399-5618.2006.00344.x . PMID   17042835.
  38. 1 2 Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. (April 2021). "Alzheimer's disease". Lancet. 397 (10284): 1577–1590. doi:10.1016/S0140-6736(20)32205-4. PMC   8354300 . PMID   33667416.
  39. 1 2 3 4 5 6 Haussmann R, Noppes F, Brandt MD, Bauer M, Donix M (August 2021). "Lithium: A therapeutic option in Alzheimer's disease and its prodromal stages?". Neuroscience Letters. 760: 136044. doi:10.1016/j.neulet.2021.136044. PMID   34119602. S2CID   235385875.
  40. 1 2 3 4 Wei HF, Anchipolovsky S, Vera R, Liang G, Chuang DM (March 2022). "Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19". European Review for Medical and Pharmacological Sciences. 26 (6): 2201–2214. doi:10.26355/eurrev_202203_28369. PMC   9173589 . PMID   35363371.
  41. ↑ Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, et al. (June 2009). "Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study". The Journal of Clinical Psychiatry. 70 (6): 922–931. doi:10.4088/JCP.08m04606. PMID   19573486.
  42. ↑ Kessing LV, Gerds TA, Knudsen NN, Jørgensen LF, Kristiansen SM, Voutchkova D, et al. (October 2017). "Association of Lithium in Drinking Water With the Incidence of Dementia". JAMA Psychiatry. 74 (10): 1005–1010. doi:10.1001/jamapsychiatry.2017.2362. PMC   5710473 . PMID   28832877.
  43. ↑ Healy D. 2005. Psychiatric Drugs Explained. 4th ed. Churchhill Livingstone: London.[ page needed ]
  44. ↑ Amdisen A (1978). "Clinical and serum level monitoring in lithium therapy and lithium intoxication". Journal of Analytical Toxicology. 2 (5): 193–202. doi:10.1093/jat/2.5.193.
  45. ↑ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 851–854. ISBN   978-0-9626523-7-0.
  46. ↑ Grandjean EM, Aubry JM (2009). "Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring". CNS Drugs. 23 (4). Springer Science and Business Media LLC: 331–349. doi:10.2165/00023210-200923040-00005. PMID   19374461. S2CID   38042857.
  47. 1 2 3 4 Gitlin M (December 2016). "Lithium side effects and toxicity: prevalence and management strategies". International Journal of Bipolar Disorders. 4 (1): 27. doi: 10.1186/s40345-016-0068-y . PMC   5164879 . PMID   27900734.
  48. ↑ Davis J, Desmond M, Berk M (November 2018). "Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification". BMC Nephrology. 19 (1). Springer Science and Business Media LLC: 305. doi: 10.1186/s12882-018-1101-4 . PMC   6215627 . PMID   30390660.
  49. ↑ Yazici O, Kora K, Polat A, Saylan M (June 2004). "Controlled lithium discontinuation in bipolar patients with good response to long-term lithium prophylaxis". Journal of Affective Disorders. 80 (2–3): 269–271. doi:10.1016/S0165-0327(03)00133-2. PMID   15207941.
  50. ↑ Gutwinski S, Fierley L, Schreiter S, Bermpohl F, Heinz A, Henssler J (October 2021). "[Lithium Withdrawal Symptoms – A Systematic Review]". Psychiatrische Praxis (in German). 48 (7). Georg Thieme Verlag KG: 341–350. doi:10.1055/a-1481-1953. PMID   34015856. S2CID   243025798.
  51. 1 2 3 DrugPoint® System (Internet). Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  52. ↑ Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty. Ltd. 2013. ISBN   978-0-9805790-8-6.
  53. ↑ Joint Formulary Committee (2013). British National Formulary (BNF) 65. London, UK: Pharmaceutical Press. pp.  240–242. ISBN   978-0-85711-084-8.
  54. ↑ "lithium (Rx) - Eskalith, Lithobid". Medscape. WebMD. Archived from the original on 4 December 2013. Retrieved 7 October 2013.
  55. ↑ "Lithobid (lithium carbonate) tablet, film coated, extended release". National Library of Medicine. Noven Therapeutics, LLC. Archived from the original on 5 October 2013. Retrieved 7 October 2013– via DailyMed.
  56. ↑ "Product Information Lithicarb (Lithium carbonate)". TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. Archived from the original on 22 March 2017. Retrieved 7 October 2013.
  57. ↑ Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, et al. (May 2015). "Effects of 10 to 30 years of lithium treatment on kidney function". Journal of Psychopharmacology. 29 (5): 608–614. doi:10.1177/0269881115573808. PMID   25735990. S2CID   9496408.
  58. ↑ Baek JH, Kinrys G, Nierenberg AA (January 2014). "Lithium tremor revisited: pathophysiology and treatment". Acta Psychiatrica Scandinavica. 129 (1). Wiley: 17–23. doi:10.1111/acps.12171. PMID   23834617. S2CID   33784257.
  59. 1 2 Strawbridge R, Young AH (January 2024). "Lithium: how low can you go?". International Journal of Bipolar Disorders. 12 (1): 4. doi: 10.1186/s40345-024-00325-y . PMC   10828288 . PMID   38289425. An in-depth recent study reported high interindividual variation but steeper declines in estimated glomerular filtration rate (eGFR) explained by lithium use but also found wrongful clinical attribution of some chronic kidney disease (CKD) cases to lithium (Fransson et al. 2022) which may have increased other records-based studies' estimates (Strawbridge and Young 2022). [...]
  60. 1 2 3 4 Kessing LV (January 2024). "Why is lithium [not] the drug of choice for bipolar disorder? a controversy between science and clinical practice". International Journal of Bipolar Disorders. 12 (1): 3. doi: 10.1186/s40345-023-00322-7 . PMC   10792154 . PMID   38228882.
  61. ↑ Ben Salem C, Fathallah N, Hmouda H, Bouraoui K (January 2011). "Drug-induced hypoglycaemia: an update". Drug Safety. 34 (1). Springer Science and Business Media LLC: 21–45. doi:10.2165/11538290-000000000-00000. PMID   20942513. S2CID   33307427.
  62. 1 2 Malhi GS, Tanious M, Bargh D, Das P, Berk M (2013). "Safe and effective use of lithium". Australian Prescriber. 36: 18–21. doi: 10.18773/austprescr.2013.008 .
  63. ↑ Silver M, Factor S (2015). "Chapter 12: VPA, lithium, amiodarone, and other non-DA". In Friedman J (ed.). Medication-Induced Movement Disorders. Cambridge University Press. pp. 131–140. ISBN   978-1-107-06600-7.
  64. ↑ Wetzels JF, van Bergeijk JD, Hoitsma AJ, Huysmans FT, Koene RA (1989). "Triamterene increases lithium excretion in healthy subjects: evidence for lithium transport in the cortical collecting tubule". Nephrology, Dialysis, Transplantation. 4 (11): 939–942. doi:10.1093/ndt/4.11.939. PMID   2516883.
  65. ↑ Keshavan MS, Kennedy JS (2001). Drug-induced dysfunction in psychiatry. Taylor & Francis. p. 305. ISBN   978-0-89116-961-1.
  66. ↑ "Safer lithium therapy". NHS National Patient Safety Agency. 1 December 2009. Archived from the original on 30 January 2010.
  67. ↑ Bendz H, Schön S, Attman PO, Aurell M (February 2010). "Renal failure occurs in chronic lithium treatment but is uncommon". Kidney International. 77 (3): 219–224. doi: 10.1038/ki.2009.433 . PMID   19940841.
  68. ↑ Lambert CG, Mazurie AJ, Lauve NR, Hurwitz NG, Young SS, Obenchain RL, et al. (May 2016). "Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort". Bipolar Disorders. 18 (3): 247–260. doi:10.1111/bdi.12391. PMC   5089566 . PMID   27226264.
  69. ↑ Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, et al. (April 2002). "Update on new developments in the study of human teratogens". Teratology. 65 (4): 153–161. doi:10.1002/tera.10032. PMID   11948561.
  70. ↑ Yacobi S, Ornoy A (2008). "Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review". The Israel Journal of Psychiatry and Related Sciences. 45 (2): 95–106. PMID   18982835.
  71. ↑ Epstein RA, Moore KM, Bobo WV (2015). "Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges". Drug, Healthcare and Patient Safety. 7: 7–29. doi: 10.2147/DHPS.S50556 . PMC   4284049 . PMID   25565896.
  72. ↑ Montouris G (June 2003). "Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry". Epilepsy & Behavior. 4 (3): 310–317. doi:10.1016/S1525-5050(03)00110-0. PMID   12791334. S2CID   902424.
  73. ↑ Weinstock L, Cohen LS, Bailey JW, Blatman R, Rosenbaum JF (2001). "Obstetrical and neonatal outcome following clonazepam use during pregnancy: a case series". Psychotherapy and Psychosomatics. 70 (3): 158–162. doi:10.1159/000056242. PMID   11340418. S2CID   25166015.
  74. ↑ "Lithium use while Breastfeeding". LactMed. 10 March 2015. Archived from the original on 8 December 2015. Retrieved 1 December 2015.
  75. ↑ "Lithium carbonate". Archived from the original on 25 October 2016. Retrieved 25 May 2016.
  76. ↑ Nielsen J, Kwon TH, Christensen BM, Frøkiaer J, Nielsen S (May 2008). "Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus". Seminars in Nephrology. 28 (3): 227–244. doi:10.1016/j.semnephrol.2008.03.002. PMID   18519084.
  77. 1 2 Alexander MP, Farag YM, Mittal BV, Rennke HG, Singh AK (January 2008). "Lithium toxicity: a double-edged sword". Kidney International. 73 (2): 233–237. doi: 10.1038/sj.ki.5002578 . PMID   17943083.
  78. ↑ Sands JM, Bichet DG (February 2006). "Nephrogenic diabetes insipidus". Annals of Internal Medicine. 144 (3): 186–194. doi:10.7326/0003-4819-144-3-200602070-00007. PMID   16461963. S2CID   6732380.
  79. ↑ Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF (April 2005). "Causes of reversible nephrogenic diabetes insipidus: a systematic review". American Journal of Kidney Diseases. 45 (4): 626–637. doi:10.1053/j.ajkd.2005.01.008. PMID   15806465.
  80. ↑ Presne C, Fakhouri F, Noël LH, Stengel B, Even C, Kreis H, et al. (August 2003). "Lithium-induced nephropathy: Rate of progression and prognostic factors". Kidney International. 64 (2): 585–592. doi: 10.1046/j.1523-1755.2003.00096.x . PMID   12846754.
  81. ↑ Davis J, Desmond M, Berk M (October 2018). "Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal". Nephrology. 23 (10). Wiley: 897–903. doi: 10.1111/nep.13263 . hdl: 11343/283773 . PMID   29607573. S2CID   4552345.
  82. ↑ "Lithium". WebMD. Archived from the original on 2 November 2014. Retrieved 1 November 2014.
  83. 1 2 3 Finley PR, O'Brien JG, Coleman RW (February 1996). "Lithium and angiotensin-converting enzyme inhibitors: evaluation of a potential interaction". Journal of Clinical Psychopharmacology. 16 (1): 68–71. doi:10.1097/00004714-199602000-00011. PMID   8834421.
  84. ↑ Oruch R, Elderbi MA, Khattab HA, Pryme IF, Lund A (October 2014). "Lithium: a review of pharmacology, clinical uses, and toxicity". European Journal of Pharmacology. 740 (740): 464–473. doi:10.1016/j.ejphar.2014.06.042. PMID   24991789.
  85. ↑ Alldredge BK, Corelli RL, Ernst ME (1 February 2012). Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs (10th ed.). Baltimore: Lippincott Williams & Wilkins. p. 1991. ISBN   978-1-60913-713-7.
  86. ↑ Boyer EW. "Serotonin syndrome". UpToDate. Wolters Kluwer. Archived from the original on 16 December 2013. Retrieved 8 October 2013.
  87. ↑ Wijdicks EF. "Neuroleptic malignant syndrome". UpToDate. Wolters Kluwer. Archived from the original on 23 October 2013. Retrieved 8 October 2013.
  88. ↑ Case reports: (Sandyk R, Hurwitz MD (November 1983). "Toxic irreversible encephalopathy induced by lithium carbonate and haloperidol. A report of 2 cases". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 64 (22): 875–876. PMID   6415823.)(Gille M, Ghariani S, Piéret F, Delbecq J, Depré A, Saussu F, et al. (May 1997). "[Acute encephalomyopathy and persistent cerebellar syndrome after lithium salt and haloperidol poisoning]". Revue Neurologique. 153 (4): 268–270. PMID   9296146.)
  89. ↑ Emilien G, Maloteaux JM (December 1996). "Lithium neurotoxicity at low therapeutic doses Hypotheses for causes and mechanism of action following a retrospective analysis of published case reports". Acta Neurologica Belgica. 96 (4): 281–293. PMID   9008777.
  90. ↑ Netto I, Phutane VH (2012). "Reversible lithium neurotoxicity: review of the literatur". The Primary Care Companion for CNS Disorders. 14 (1): PCC.11r01197. doi:10.4088/PCC.11r01197. PMC   3357580 . PMID   22690368.
  91. ↑ Nayak SM, Gukasyan N, Barrett FS, Erowid E, Erowid F, Griffiths RR (September 2021). "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports". Pharmacopsychiatry. 54 (5): 240–245. doi: 10.1055/a-1524-2794 . PMID   34348413.
  92. ↑ Netto I, Phutane VH (2012). "Reversible lithium neurotoxicity: review of the literatur". The Primary Care Companion for CNS Disorders. 14 (1). doi:10.4088/PCC.11r01197. PMC   3357580 . PMID   22690368.
  93. 1 2 Brunton L, Chabner B, Knollman B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN   978-0-07-162442-8.
  94. ↑ Massot O, Rousselle JC, Fillion MP, Januel D, Plantefol M, Fillion G (October 1999). "5-HT1B receptors: a novel target for lithium. Possible involvement in mood disorders". Neuropsychopharmacology. 21 (4): 530–541. doi: 10.1016/S0893-133X(99)00042-1 . PMID   10481837.
  95. ↑ Scheuch K, Höltje M, Budde H, Lautenschlager M, Heinz A, Ahnert-Hilger G, et al. (January 2010). "Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons". Brain Research. 1307: 14–21. doi:10.1016/j.brainres.2009.10.027. PMID   19840776. S2CID   6045269.
  96. 1 2 3 Malhi GS, Masson M, Bellivier F (2017). The Science and Practice of Lithium Therapy. Springer International Publishing. p. 62. ISBN   978-3-319-45923-3. OCLC   979600268.
  97. ↑ Einat H, Manji HK (June 2006). "Cellular plasticity cascades: genes-to-behavior pathways in animal models of bipolar disorder". Biological Psychiatry. 59 (12): 1160–1171. doi:10.1016/j.biopsych.2005.11.004. PMID   16457783. S2CID   20669215.
  98. ↑ Gould TD, Picchini AM, Einat H, Manji HK (November 2006). "Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disorders". Current Drug Targets. 7 (11): 1399–1409. doi:10.2174/1389450110607011399. PMID   17100580.
  99. ↑ Böer U, Cierny I, Krause D, Heinrich A, Lin H, Mayr G, et al. (September 2008). "Chronic lithium salt treatment reduces CRE/CREB-directed gene transcription and reverses its upregulation by chronic psychosocial stress in transgenic reporter gene mice". Neuropsychopharmacology. 33 (10): 2407–2415. doi: 10.1038/sj.npp.1301640 . PMID   18046304.
  100. ↑ Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, et al. (January 2011). "Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors". Neuroscience and Biobehavioral Reviews. 35 (3): 804–817. doi:10.1016/j.neubiorev.2010.10.001. PMID   20934453. S2CID   11421586.
  101. ↑ York JD, Ponder JW, Majerus PW (May 1995). "Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure". Proceedings of the National Academy of Sciences of the United States of America. 92 (11): 5149–5153. Bibcode:1995PNAS...92.5149Y. doi: 10.1073/pnas.92.11.5149 . PMC   41866 . PMID   7761465.
  102. ↑ Yenush L, Bellés JM, López-Coronado JM, Gil-Mascarell R, Serrano R, Rodríguez PL (February 2000). "A novel target of lithium therapy". FEBS Letters. 467 (2–3): 321–325. Bibcode:2000FEBSL.467..321Y. doi: 10.1016/s0014-5793(00)01183-2 . PMID   10675562. S2CID   43250471.
  103. ↑ Toledano E, Ogryzko V, Danchin A, Ladant D, Mechold U (April 2012). "3'-5' phosphoadenosine phosphate is an inhibitor of PARP-1 and a potential mediator of the lithium-dependent inhibition of PARP-1 in vivo". The Biochemical Journal. 443 (2): 485–490. doi:10.1042/BJ20111057. PMC   3316155 . PMID   22240080.
  104. ↑ Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR (May 2008). "Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test". European Neuropsychopharmacology. 18 (5): 323–332. doi:10.1016/j.euroneuro.2007.07.011. PMID   17728109. S2CID   44805917.
  105. ↑ Ghasemi M, Sadeghipour H, Poorheidari G, Dehpour AR (June 2009). "A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test". Behavioural Brain Research. 200 (1): 76–82. doi:10.1016/j.bbr.2008.12.032. PMID   19166880. S2CID   22656735.
  106. ↑ Ghasemi M, Raza M, Dehpour AR (April 2010). "NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test". Journal of Psychopharmacology. 24 (4): 585–594. doi:10.1177/0269881109104845. PMID   19351802. S2CID   41634565.
  107. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Malhi GS, Tanious M, Das P, Coulston CM, Berk M (February 2013). "Potential mechanisms of action of lithium in bipolar disorder. Current understanding". CNS Drugs. 27 (2): 135–153. doi:10.1007/s40263-013-0039-0. hdl: 11343/218106 . PMID   23371914. S2CID   26907074.
  108. ↑ Birch NJ (2 December 2012). Lithium and the Cell: Pharmacology and Biochemistry. Academic Press. ISBN   978-0-08-098429-2. Archived from the original on 26 February 2024. Retrieved 9 October 2020.
  109. ↑ Brunello N, Tascedda F (June 2003). "Cellular mechanisms and second messengers: relevance to the psychopharmacology of bipolar disorders". The International Journal of Neuropsychopharmacology. 6 (2): 181–189. doi: 10.1017/s1461145703003419 . hdl: 11380/305821 . PMID   12890311.
  110. ↑ Malhi GS, Masson M, Bellivier F (2017). The Science and Practice of Lithium Therapy. Springer International Publishing. p. 61. ISBN   978-3-319-45923-3. OCLC   979600268.
  111. ↑ Alda M (June 2015). "Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics". Molecular Psychiatry. 20 (6): 661–670. doi:10.1038/mp.2015.4. PMC   5125816 . PMID   25687772.
  112. ↑ Einat H, Kofman O, Itkin O, Lewitan RJ, Belmaker RH (1998). "Augmentation of lithium's behavioral effect by inositol uptake inhibitors". Journal of Neural Transmission. 105 (1): 31–38. doi:10.1007/s007020050035. PMID   9588758. S2CID   6707456.
  113. ↑ Jope RS (March 1999). "Anti-bipolar therapy: mechanism of action of lithium". Molecular Psychiatry. 4 (2): 117–128. doi: 10.1038/sj.mp.4000494 . PMID   10208444.
  114. ↑ Abu-Hijleh FA, Prashar S, Joshi H, Sharma R, Frey BN, Mishra RK (February 2021). "Novel mechanism of action for the mood stabilizer lithium". Bipolar Disorders. 23 (1): 76–83. doi:10.1111/bdi.13019. PMID   33037686. S2CID   222257563.
  115. 1 2 Marmol F (December 2008). "Lithium: bipolar disorder and neurodegenerative diseases Possible cellular mechanisms of the therapeutic effects of lithium". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 32 (8): 1761–1771. doi:10.1016/j.pnpbp.2008.08.012. PMID   18789369. S2CID   25861243.
  116. ↑ "Lithium: Discovered, Forgotten and Rediscovered". inhn.org. Archived from the original on 12 March 2023. Retrieved 12 March 2023.
  117. ↑ "Obituary – Shirley Aldythea Andrews – Obituaries Australia". oa.anu.edu.au. Archived from the original on 26 October 2022. Retrieved 26 October 2022.
  118. ↑ Cade JF (September 1949). "Lithium salts in the treatment of psychotic excitement" (PDF). The Medical Journal of Australia. 2 (10): 349–352. doi:10.1080/j.1440-1614.1999.06241.x. PMC   2560740 . PMID   18142718. Archived (PDF) from the original on 25 May 2006.
  119. ↑ Fieve RR (December 1999). "Lithium therapy at the millennium: a revolutionary drug used for 50 years faces competing options and possible demise". Bipolar Disorders. 1 (2): 67–70. doi:10.1034/j.1399-5618.1999.010201.x. PMID   11252660.
  120. ↑ Mitchell PB, Hadzi-Pavlovic D (2000). "Lithium treatment for bipolar disorder" (PDF). Bulletin of the World Health Organization. 78 (4): 515–517. PMC   2560742 . PMID   10885179. Archived (PDF) from the original on 25 May 2006.
  121. ↑ Agassi T (12 March 1996). "Sting is now older, wiser and duller". The Jerusalem Post . Archived from the original on 13 May 2012. Retrieved 25 June 2009.
  122. ↑ "7 UP: The Making of a Legend". Cadbury Schweppes: America's Beverages.
  123. ↑ "Urban Legends Reference Pages: 7Up". 6 August 2004. Archived from the original on 6 May 2023. Retrieved 13 November 2007.
  124. ↑ anonymous (13 July 1950). "ISALLY'S (ad)". Painesville Telegraph. Archived from the original on 28 August 2021. Retrieved 8 September 2013.
  125. 1 2 Wen J, Sawmiller D, Wheeldon B, Tan J (17 January 2020). "A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity". CNS & Neurological Disorders Drug Targets. 18 (10): 769–778. doi:10.2174/1871527318666191114095249. PMID   31724518. S2CID   208019043.
  126. ↑ "How and when to take lithium". nhs.uk. 14 August 2023. Archived from the original on 26 October 2023. Retrieved 6 December 2023.
  127. ↑ Forlenza OV, de Paula VJ, Machado-Vieira R, Diniz BS, Gattaz WF (May 2012). "Does lithium prevent Alzheimer's disease?". Drugs & Aging. 29 (5): 335–342. doi:10.2165/11599180-000000000-00000. PMID   22500970. S2CID   23864616.
  128. ↑ Wilson EN, Do Carmo S, Welikovitch LA, Hall H, Aguilar LF, Foret MK, et al. (2020). "NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats". Journal of Alzheimer's Disease. 73 (2): 723–739. doi:10.3233/JAD-190862. PMID   31868669. S2CID   209448822.
  129. ↑ Ludolph AC, Brettschneider J, Weishaupt JH (October 2012). "Amyotrophic lateral sclerosis". Current Opinion in Neurology. 25 (5): 530–535. doi:10.1097/WCO.0b013e328356d328. PMID   22918486.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.