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Մասնակից:Nunn Ghazaryan/Ավազարկղ2

Վիքիպեդիայից՝ ազատ հանրագիտարանից


Լիթիումի որոշ միացություններ, որոնք նաև հայտնի են որպես լիթիումի աղեր, օգտագործվում են որպես հոգեբուժական դեղամիջոց[1], հիմնականում երկբևեռ աֆեկտի խանգարման և խոշոր դեպրեսիվ խանգարման համար[1]: Լիթիումը ներքին ընդունման համար է (բերանի միջոցով)[1]:

Հաճախակի կողմնակի ազդեցությունները ներառում են միզարձակման ավելացում, ձեռքերի դող և ծարավի զգացում[1]: Լուրջ կողմնակի ազդեցությունները ներառում են հիպոթիրեոզ, շաքարային դիաբետ և լիթիումի թունավորում[1]: Արյան մակարդակի մոնիտորինգը խորհուրդ է տրվում նվազեցնել պոտենցիալ թունավորման ռիսկը[1]: Եթե ​​մակարդակը շատ բարձրանա, կարող է առաջանալ փորլուծութուն, փսխում, քնկոտություն և ականջներում աղմուկ[1]: Լիթիումը տերատոգեն (հրեշածին) է բարձր չափաբաժիններով, հատկապես հղիության առաջին եռամսյակում: Կրծքով կերակրման ժամանակ լիթիումի օգտագործումը անթույլատրելի է: Այնուամենայնիվ, բազմաթիվ միջազգային առողջապահական մարմիններ խորհուրդ չեն տալիս դա անել, և լիթիումի ազդեցության երկարաժամկետ արդյունքները ուսումնասիրված չեն[2]: Ամերիկյան մանկաբուժության ակադեմիան նշում է, որ լիթիումը հակացուցված է հղիության և լակտացիայի ժամանակ[3]: Միացյալ Նահանգների Սննդամթերքի և դեղերի վարչությունը լիթիումը դասակարգում է որպես հղիության ռիսկի և լակտացիայի համար հնարավոր վտանգավոր ապացույց[3][4]:

Լիթիումի աղերը դասակարգվում են որպես տրամադրության կայունացուցիչներ[1]: Լիթիումի ազդման մեխանիզմը հայտնի չէ[1]:

19-րդ դարում լիթիումը օգտագործվում էր հոդատապով, էպիլեպսիայով և քաղցկեղով տառապող մարդկանց շրջանում[5]: Դրա կիրառումը հոգեկան խանգարումների բուժման համար սկսվել է Դանիայում Կարլ Լանգեից[6] և Վիլյամ Ալեքսանդր Համոնդից Նյու Յորքում[7], ովքեր օգտագործում էին լիթիումը 1870-ական թվականներից սկսած խելագարությունը բուժելու համար՝ հիմնվելով այժմ անհավաստի տեսությունների վրա, որոնք վերաբերում էին դրա ազդեցությանը միզաթթվի վրա: Լիթիումի օգտագործումը հոգեկան խանգարումների համար վերահաստատվել է (տարբեր տեսական հիմունքներով) 1948 թվականին Ջոն Քեյդի կողմից Ավստրալիայում[5]: Լիթիումի կարբոնատը Առողջապահության համաշխարհային կազմակերպության հիմնական դեղամիջոցների ցանկում է[8], և հասանելի է որպես ընդհանուր դեղամիջոց[1]: 2020 թվականին այն ԱՄՆ-ում 197-րդ ամենատարածված դեղամիջոցն էր՝ ավելի քան 2 միլիոն դեղատոմսով[9][10]: Աայն քիչ է օգտագործվում տարեց մարդկանց մոտ[11], չնայած դրա պատճառը պարզ չէ:

Կիրառությունը բժշկության մեջ

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Լիթիումի դեղամիջոցի շիշ, որը պարունակում է 300 մգ լիթիումի կարբոնատ պատիճ:

1970 թվականին լիթիումը հաստատվել է Միացյալ Նահանգների Սննդի և Դեղերի Ադմինիստրացիայի կողմից (FDA) երկբևեռ աֆեկտի խանգարման բուժման համար, որը մնում է դրա հիմնական օգտագործումը Միացյալ Նահանգներում[1][12]: Այն երբեմն օգտագործվում է, երբ այլ բուժումները արդյունավետ չեն մի շարք այլ պայմանների դեպքում, ներառյալ ծանր դեպրեսիան[13], շիզոֆրենիան, իմպուլսների վերահսկման խանգարումները և որոշ հոգեբուժական խանգարումներ երեխաների մոտ[1]: Քանի որ FDA-ն չի հաստատել լիթիումը այլ խանգարումների բուժման համար, նման օգտագործումը պիտակավորված չէ[14][13]:

Երկբևեռ աֆերենտ խանգարում

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Լիթիումը հիմնականում օգտագործվում է որպես պահպանող դեղամիջոց երկբևեռ խանգարման բուժման համար՝ տրամադրությունը կայունացնելու և մոլագար դրվագները կանխելու համար, բայց այն կարող է նաև օգտակար լինել մոլագարության սուր բուժման համար[15]: Թեև առաջարկվում է երկբևեռ խանգարման դեպքում դեպրեսիայի բուժման ուղեցույցներով, սակայն ապացույցը, որ սուր դեպրեսիայի դեպքում լիթիումը գերազանցում է պլացեբոյին, ցածր որակի է[16][17]: Ատիպիկ հակափսիխոտիկները համարվում են ավելի արդյունավետ սուր դեպրեսիվ խանգարումներիի բուժման համար[18]: Լիթիումի կարբոնատով բուժումը նախկինում կիրառելի չէր երեխաների համար, աԱյնուամենայնիվ, վերջին ուսումնասիրությունները ցույց են տալիս դրա արդյունավետությունը ութ տարեկանից փոքր երեխաների մոտ վաղ սկիզբ առած երկբևեռ խանգարման բուժման համար: Պահանջվող դեղաչափը մի փոքր պակաս է թունավոր մակարդակից (ներկայացնում է ցածր թերապևտիկ ինդեքս), որը պահանջում է արյան մեջ լիթիումի կարբոնատի մակարդակիվերահսկումր բուժման ընթացքում[19]: Թերապևտիկ տիրույթում առկա է դոզայի արձագանքման հարաբերություն[20]: Ապացույցների սահմանափակ քանակությունը ցույց է տալիս, որ լիթիումի կարբոնատը կարող է նպաստել երկբևեռ խանգարում ունեցող որոշ մարդկանց թմրամիջոցների օգտագործման խանգարումների բուժմանը[21][22][23]: Թեև ենթադրվում է, որ լիթիումը կանխում է ինքնասպանությունը երկբևեռ խանգարում ունեցող մարդկանց մոտ, 2022 թվականի համակարգված վերանայումը ցույց է տվել, որ «պատահական փորձարկումների ապացույցները վերջնական չեն և չեն հաստատում այն ​​գաղափարը, որ լիթիումը կանխում է ինքնասպանությունը կամ ինքնասպանության դրդումը»[24]:

Շիզոֆրենիկ խանգարումներ

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Լիթիումը խորհուրդ է տրվում շիզոֆրենիկ խանգարումների բուժման համար միայն այն բանից հետո, երբ այլ հակահոգեբուժական միջոցները այլևս չեն օգնում, այն ունի սահմանափակ արդյունավետություն առանձին օգտագործման դեպքում[1]: Շիզոֆրենիայի խանգարումների բուժման համար լիթիումի հակահոգեբուժական թերապիայի հետ համատեղելու արդյունավետության տարբեր կլինիկական հետազոտությունների արդյունքները տարբեր են[1]:

Հիմնական դեպրեսիվ խանգարում

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Եթե ​​հիմնական դեպրեսիվ խանգարման ախտանշանները չեն համապատասխանում ստանդարտ բուժմանը, երբեմն ավելացվում է երկրորդ դեղամիջոց: Վերջերս իրականացված համակարգված տեսութունը հայտնաբերել է լիթիումի կլինիկական օգտակարության որոշ լրացուցիչ ապացույցներ, սակայն օժանդակ ապացույցների մեծ մասը թվագրված է: Նույն տեսութունը չի գտել որևէ ապացույց, որը կաջակցի լիթիումի օգտագործումը մոնոթերապիայի համար[25]:

Կան մի քանի հին ուսումնասիրություններ, որոնք ցույց են տալիս լիթիումի արդյունավետությունը սուր դեպրեսիայի դեպքում, որն ունի նույն արդյունավետությունը, ինչ տրիցիկլիկ հակադեպրեսանտները[26]: Վերջերս կատարված ուսումնասիրությունը եզրակացրեց, որ լիթիումը լավագույնս աշխատում է քրոնիկական և կրկնվող դեպրեսիայի դեպքում՝ համեմատած ժամանակակից հակադեպրեսանտների (այսինքն՝ ցիտալոպրամի) հետ, բայց ոչ դեպրեսիայի պատմություն չունեցող հիվանդների համար[27]:

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.[28][29][30][31][32][33]

Alzheimer's disease affects forty-five million people and is the fifth leading cause of death in the 65 plus population.[34]Կաղապար: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.[34] To combat this toxic amyloid aggregation, lithium upregulates the production of neuroprotectors and neurotrophic factors, as well as inhibiting the GSK-3 enzyme.[35] Lithium also stimulates neurogenesis within the hippocampus, making it thicker.[35] Yet another cause of Alzheimer's disease is the dysregulation of calcium ions within the brain.[36] Too much or too little calcium within the brain can lead to cell death.[36] Lithium is able to restore the intracellular calcium homeostasis through inhibiting the wrongful influx of calcium upstream.[36] 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.[36]

In 2009, a study was performed by Hampel and colleagues[37] 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.[35] 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.[35] Another study, a population study this time by Kessing et al.,[38] showed a negative correlation between Alzheimer's disease deaths and the presence of lithium in drinking water.[35] Areas with increased lithium in their drinking water showed less dementia overall in their population.[35]

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.[39]

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.[40][41]

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[Ն 1][Ն 2] to 1.2 mmol/L [42] 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.[43]

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.[44]

For patients who have achieved long term remission, it is recommended to discontinue lithium gradually and in a controlled fashion.[45][26]

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. [46]

Cluster headaches, migraine and hypnic headache

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Studies testing prophylactic use of lithium in cluster headaches (when compared to verapamil), migraine attacks and hypnic headache indicate good efficacy.[26]

The adverse effects of lithium include:[47][48][49][50][51][52][53]

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

Lithium carbonate can induce a 1–2 kg of weight gain.[58]

In addition to tremors, lithium treatment appears to be a risk factor for development of parkinsonism-like symptoms, although the causal mechanism remains unknown.[59]

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

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.[58]

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.[60] It increases the appetite and thirst ("polydypsia") and reduces the activity of thyroid hormone (hypothyroidism).[61][62] The latter can be corrected by treatment with thyroxine and does not require the lithium dose to be adjusted. Lithium is also believed to permanently affect renal functionԿաղապար:How, although this does not appear to be common.[63]

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 – only 1.39 times the rate in oxcarbazepine users. 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 argue that there may be an element of surveillance bias in understanding lithium's effects on the thyroid glands.[64][56]

Pregnancy and breast feeding

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Lithium is a teratogen, causing birth defects in a small number of newborn babies.[65] 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.[66] 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.[67] Gabapentin[68] and clonazepam[69] 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[70] including the British National Formulary.[71]

Lithium has been associated with several forms of kidney injury.[72][73] 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.[73] Continued use of lithium can lead to more serious kidney damage in an aggravated form of diabetes insipidus.[74][75] 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%.[76]

Some reports of kidney damage may be attributed to lithium, increasing the apparent rate of this adverse effect.[55] 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.[56] 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.[77]

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.[56]

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.

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.[47] Lithium concentrations can also be increased with concurrent use of ACE inhibitors such as captopril, enalapril, and lisinopril.[78]

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.[79] 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.[79][80] 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.[79]

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.[81]

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.[47][82] Lithium co-treatment is also a risk factor for neuroleptic malignant syndrome in people on antipsychotics and other antidopaminergic medications.[83]

High doses of haloperidol, fluphenazine, or flupenthixol may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported.[84] Indeed, these and other antipsychotics have been associated with increased risk of lithium neurotoxicity, even with low therapeutic lithium doses.[85][86]

Classical psychedelics such as psilocybin and LSD may cause seizures if taken while using lithium, although further research is needed.[87]

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.[43]

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.[88]

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.

The specific biochemical mechanism of lithium action in stabilizing mood is unknown.[1]

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.[89]

Unlike many other psychoactive drugs, Li+
typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations.[89] Lithium may also increase the release of serotonin by neurons in the brain.[90] 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.[91]

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.[92] GSK-3β is a downstream target of monoamine systems. As such, it is directly implicated in cognition and mood regulation.[93][92] During mania, GSK-3β is activated via dopamine overactivity.[92] 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.[94][95][96] In addition, several authors proposed that pAp-phosphatase could be one of the therapeutic targets of lithium.[97][98] 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.[99]

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.[100][101] It was also reported that NMDA receptor blockage augments antidepressant-like effects of lithium in the mouse forced swimming test,[102] 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.[103]

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.[104]

Evidence suggests that mitochondrial dysfunction is present in patients with bipolar disorder.[103] 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.[103]

Dopamine and G-protein coupling

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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.[103] 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.[103] Lithium treatment alters the function of certain subunits of the dopamine associated G-protein, which may be part of its mechanism of action.[103]

Glutamate and NMDA receptors

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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.[103] 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.[103] 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.[103]

GABA is an inhibitory neurotransmitter that plays an important role in regulating dopamine and glutamate neurotransmission.[103] 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.[105] Lithium counteracts these degrading processes by decreasing pro-apoptotic proteins and stimulating release of neuroprotective proteins.[103] Lithium's regulation of both excitatory dopaminergic and glutamatergic systems through GABA may play a role in its mood stabilizing effects.[106]

Cyclic AMP secondary messengers

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Lithium's therapeutic effects are thought to be partially attributable to its interactions with several signal transduction mechanisms.[107] 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.[103] It is hypothesized that the dual effects of lithium are due to the inhibition of G-proteins that mediate cyclic AMP production.[103] Over a long period of lithium treatment, cyclic AMP and adenylate cyclase levels are further changed by gene transcription factors.[103]

Inositol depletion hypothesis

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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.[108] 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.[109] 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.[103] Reductions of cellular levels of myo-inositol results in the inhibition of the phosphoinositide cycle.[103]

Various neurotrophic factors such as BDNF and mesencephalic astrocyte-derived neurotrophic factor have been shown to be modulated by various mood stabilizers.[110]

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.[111] Because of prevalent theories linking excess uric acid to a range of disorders, including depressive and manic disorders, Carl Lange in Denmark[6] and William Alexander Hammond in New York City[7] 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.[14] 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.[112]

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.[113] 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.[114]

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,[111] 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[115]), the application of lithium in manic illness was approved by the United States Food and Drug Administration in 1970,[116] becoming the 50th nation to do so.[14] 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,[117] and "Lithium" by Thin White Rope.

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.[118] 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.[119] 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.[120]

Salts and product names

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Lithium carbonate (Li
2
CO
3
) is the most commonly used form of lithium, although lithium citrate (Li
3
C
6
H
5
O
7
) and other salts, including lithium sulfate, lithium chloride, and lithium orotate are also used.[121][122] 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.[121]

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.[123]

Tentative evidence in Alzheimer's disease showed that lithium may slow progression.[124][125] 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.[126]

  1. 1,00 1,01 1,02 1,03 1,04 1,05 1,06 1,07 1,08 1,09 1,10 1,11 1,12 1,13 1,14 «Lithium Salts». The American Society of Health-System Pharmacists. Արխիվացված օրիգինալից 8 December 2015-ին. Վերցված է 1 December 2015-ին.
  2. 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.
  3. 3,0 3,1 Armstrong C (15 September 2008). «ACOG Guidelines on Psychiatric Medication Use During Pregnancy and Lactation». American Family Physician. 78 (6): 772. ISSN 0002-838X. Արխիվացված օրիգինալից 27 January 2022-ին. Վերցված է 27 January 2022-ին.
  4. «Lithium Carbonate Medication Guide» (PDF). U.S. FDA. Արխիվացված (PDF) օրիգինալից 27 January 2022-ին. Վերցված է 27 January 2022-ին.
  5. 5,0 5,1 Sneader W (2005). Drug discovery : a history (Rev. and updated ed.). Chichester: Wiley. էջ 63. ISBN 978-0-471-89979-2. Արխիվացված օրիգինալից 8 September 2017-ին.
  6. 6,0 6,1 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.
  7. 7,0 7,1 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. Արխիվացված է օրիգինալից (PDF) 1 April 2012-ին.
  8. 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.
  9. «The Top 300 of 2020». ClinCalc. Արխիվացված օրիգինալից 26 March 2023-ին. Վերցված է 7 October 2022-ին.
  10. «Lithium – Drug Usage Statistics». ClinCalc. Արխիվացված օրիգինալից 10 June 2023-ին. Վերցված է 7 October 2022-ին.
  11. 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 (English). 31 (9): 716–725. doi:10.1016/j.jagp.2023.03.012. ISSN 1064-7481. PMID 37080815. S2CID 257824414. Արխիվացված օրիգինալից 31 March 2023-ին. Վերցված է 31 March 2023-ին.{{cite journal}}: CS1 սպաս․ չճանաչված լեզու (link)
  12. 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 (անգլերեն). American Association for Clinical Chemistry. էջ 170. ISBN 978-0-915274-22-2. Արխիվացված օրիգինալից 26 February 2024-ին. Վերցված է 27 May 2022-ին.
  13. 13,0 13,1 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.
  14. 14,0 14,1 14,2 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Semple, David "Oxford Hand Book of Psychiatry" Oxford Press. 2005.[Հղում աղբյուրներին]
  20. Hsu CW, Tsai SY, Tseng PT, Liang CS, Vieta E, Carvalho AF, Stubbs B, Kao HY, Tu YK, Lin PY (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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Undurraga J, Sim K, Tondo L, Gorodischer A, Azua E, Tay KH, Tan D, Baldessarini RJ (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. Արխիվացված օրիգինալից 20 February 2024-ին. Վերցված է 20 February 2024-ին.
  26. 26,0 26,1 26,2 Bauer M, Grof P, Muller-Oerlinghausen B (2006). Lithium in Neuropsychiatry: The Comprehensive Guide. Taylor & Francis. ISBN 978-1-84184-515-9. Արխիվացված օրիգինալից 26 February 2024-ին. Վերցված է 17 July 2021-ին.
  27. Bauer M, Gitlin M (2016). «Treatment of Depression with Lithium». The Essential Guide to Lithium Treatment. Cham: Springer International Publishing. էջեր 71–80. doi:10.1007/978-3-319-31214-9_7. ISBN 978-3-319-31212-5.
  28. 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.
  29. Del Matto L, Muscas M, Murru A, Verdolini N, Anmella G, Fico G, Corponi F, Carvalho AF, Samalin L, Carpiniello B, Fagiolini A, Vieta E, Pacchiarotti I (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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 34,0 34,1 Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM (April 2021). «Alzheimer's disease». Lancet. 397 (10284): 1577–1590. doi:10.1016/S0140-6736(20)32205-4. PMC 8354300. PMID 33667416.
  35. 35,0 35,1 35,2 35,3 35,4 35,5 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.
  36. 36,0 36,1 36,2 36,3 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.
  37. Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H (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.
  38. Kessing LV, Gerds TA, Knudsen NN, Jørgensen LF, Kristiansen SM, Voutchkova D, Ernstsen V, Schullehner J, Hansen B, Andersen PK, Ersbøll AK (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.
  39. Healy D. 2005. Psychiatric Drugs Explained. 4th ed. Churchhill Livingstone: London.[Հղում աղբյուրներին]
  40. 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.
  41. Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. էջեր 851–854. ISBN 978-0-9626523-7-0.
  42. Grandjean EM, Aubry JM (2009). «Lithium: updated human knowledge using an evidence-based approach. Part II: Clinical pharmacology and therapeutic monitoring». CNS Drugs. Springer Science and Business Media LLC. 23 (4): 331–349. doi:10.2165/00023210-200923040-00005. PMID 19374461. S2CID 38042857.
  43. 43,0 43,1 43,2 43,3 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.
  44. Davis J, Desmond M, Berk M (November 2018). «Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification». BMC Nephrology. Springer Science and Business Media LLC. 19 (1): 305. doi:10.1186/s12882-018-1101-4. PMC 6215627. PMID 30390660.
  45. 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.
  46. Gutwinski S, Fierley L, Schreiter S, Bermpohl F, Heinz A, Henssler J (October 2021). «[Lithium Withdrawal Symptoms – A Systematic Review]». Psychiatrische Praxis (գերմաներեն). Georg Thieme Verlag KG. 48 (7): 341–350. doi:10.1055/a-1481-1953. PMID 34015856. S2CID 243025798.
  47. 47,0 47,1 47,2 DrugPoint® System (Internet). Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  48. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty. Ltd. 2013. ISBN 978-0-9805790-8-6.
  49. Joint Formulary Committee (2013). British National Formulary (BNF) 65. London, UK: Pharmaceutical Press. էջեր 240–242. ISBN 978-0-85711-084-8.
  50. «lithium (Rx) - Eskalith, Lithobid». Medscape. WebMD. Արխիվացված օրիգինալից 4 December 2013-ին. Վերցված է 7 October 2013-ին.
  51. «Lithobid (lithium carbonate) tablet, film coated, extended release». National Library of Medicine. Noven Therapeutics, LLC. Արխիվացված օրիգինալից 5 October 2013-ին. Վերցված է 7 October 2013-ին – via DailyMed.
  52. «Product Information Lithicarb (Lithium carbonate)». TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. Արխիվացված օրիգինալից 22 March 2017-ին. Վերցված է 7 October 2013-ին.
  53. Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, Svedlund J (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.
  54. Baek JH, Kinrys G, Nierenberg AA (January 2014). «Lithium tremor revisited: pathophysiology and treatment». Acta Psychiatrica Scandinavica. Wiley. 129 (1): 17–23. doi:10.1111/acps.12171. PMID 23834617. S2CID 33784257.
  55. 55,0 55,1 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). [...]»
  56. 56,0 56,1 56,2 56,3 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.
  57. Ben Salem C, Fathallah N, Hmouda H, Bouraoui K (January 2011). «Drug-induced hypoglycaemia: an update». Drug Safety. Springer Science and Business Media LLC. 34 (1): 21–45. doi:10.2165/11538290-000000000-00000. PMID 20942513. S2CID 33307427.
  58. 58,0 58,1 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.
  59. 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. էջեր 131–140. ISBN 978-1-107-06600-7.
  60. 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.
  61. Keshavan MS, Kennedy JS (2001). Drug-induced dysfunction in psychiatry. Taylor & Francis. էջ 305. ISBN 978-0-89116-961-1.
  62. «Safer lithium therapy». NHS National Patient Safety Agency. 1 December 2009. Արխիվացված է օրիգինալից 30 January 2010-ին.
  63. 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.
  64. Lambert CG, Mazurie AJ, Lauve NR, Hurwitz NG, Young SS, Obenchain RL, Hengartner NW, Perkins DJ, Tohen M, Kerner B (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.
  65. Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, Polifka JE (April 2002). «Update on new developments in the study of human teratogens». Teratology. 65 (4): 153–161. doi:10.1002/tera.10032. PMID 11948561.
  66. 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.
  67. 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.
  68. 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.
  69. 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.
  70. «Lithium use while Breastfeeding». LactMed. 10 March 2015. Արխիվացված օրիգինալից 8 December 2015-ին. Վերցված է 1 December 2015-ին.
  71. «Lithium carbonate». Արխիվացված է օրիգինալից 25 October 2016-ին. Վերցված է 25 May 2016-ին.
  72. 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.
  73. 73,0 73,1 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.
  74. 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.
  75. 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.
  76. Presne C, Fakhouri F, Noël LH, Stengel B, Even C, Kreis H, Mignon F, Grünfeld JP (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.
  77. Davis J, Desmond M, Berk M (October 2018). «Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal». Nephrology. Wiley. 23 (10): 897–903. doi:10.1111/nep.13263. hdl:11343/283773. PMID 29607573. S2CID 4552345.
  78. «Lithium». WebMD. Արխիվացված օրիգինալից 2 November 2014-ին. Վերցված է 1 November 2014-ին.
  79. 79,0 79,1 79,2 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.
  80. 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.
  81. 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. էջ 1991. ISBN 978-1-60913-713-7.
  82. Boyer EW. «Serotonin syndrome». UpToDate. Wolters Kluwer. Արխիվացված օրիգինալից 16 December 2013-ին. Վերցված է 8 October 2013-ին.
  83. Wijdicks EF. «Neuroleptic malignant syndrome». UpToDate. Wolters Kluwer. Արխիվացված օրիգինալից 23 October 2013-ին. Վերցված է 8 October 2013-ին.
  84. 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, de Barsy T (May 1997). «[Acute encephalomyopathy and persistent cerebellar syndrome after lithium salt and haloperidol poisoning]». Revue Neurologique. 153 (4): 268–270. PMID 9296146.)
  85. 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.
  86. 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.
  87. 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.
  88. 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.
  89. 89,0 89,1 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.
  90. 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.
  91. Scheuch K, Höltje M, Budde H, Lautenschlager M, Heinz A, Ahnert-Hilger G, Priller J (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.
  92. 92,0 92,1 92,2 Malhi GS, Masson M, Bellivier F (2017). The Science and Practice of Lithium Therapy. Springer International Publishing. էջ 62. ISBN 978-3-319-45923-3. OCLC 979600268.
  93. 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.
  94. 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.
  95. Böer U, Cierny I, Krause D, Heinrich A, Lin H, Mayr G, Hiemke C, Knepel W (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.
  96. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (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.
  97. 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.
  98. 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.
  99. 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.
  100. 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.
  101. 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.
  102. 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.
  103. 103,00 103,01 103,02 103,03 103,04 103,05 103,06 103,07 103,08 103,09 103,10 103,11 103,12 103,13 103,14 103,15 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.
  104. Birch NJ (2 December 2012). Lithium and the Cell: Pharmacology and Biochemistry. Academic Press. ISBN 978-0-08-098429-2. Արխիվացված օրիգինալից 26 February 2024-ին. Վերցված է 9 October 2020-ին.
  105. 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.
  106. Malhi GS, Masson M, Bellivier F (2017). The Science and Practice of Lithium Therapy. Springer International Publishing. էջ 61. ISBN 978-3-319-45923-3. OCLC 979600268.
  107. 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.
  108. 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.
  109. 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.
  110. 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.
  111. 111,0 111,1 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.
  112. «Lithium: Discovered, Forgotten and Rediscovered». inhn.org. Արխիվացված օրիգինալից 12 March 2023-ին. Վերցված է 12 March 2023-ին.
  113. «Obituary – Shirley Aldythea Andrews – Obituaries Australia». oa.anu.edu.au. Արխիվացված օրիգինալից 26 October 2022-ին. Վերցված է 26 October 2022-ին.
  114. 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. Արխիվացված (PDF) օրիգինալից 25 May 2006-ին.
  115. 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.
  116. 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. Արխիվացված (PDF) օրիգինալից 25 May 2006-ին.
  117. Agassi T (12 March 1996). «Sting is now older, wiser and duller». The Jerusalem Post. Արխիվացված օրիգինալից 13 May 2012-ին. Վերցված է 25 June 2009-ին.
  118. "7 UP: The Making of a Legend". Cadbury Schweppes: America's Beverages.
  119. «Urban Legends Reference Pages: 7Up». 6 August 2004. Արխիվացված օրիգինալից 6 May 2023-ին. Վերցված է 13 November 2007-ին.
  120. anonymous (13 July 1950). «ISALLY'S (ad)». Painesville Telegraph. Արխիվացված օրիգինալից 28 August 2021-ին. Վերցված է 8 September 2013-ին.
  121. 121,0 121,1 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.
  122. «How and when to take lithium». nhs.uk (անգլերեն). 14 August 2023. Արխիվացված օրիգինալից 26 October 2023-ին. Վերցված է 6 December 2023-ին.
  123. «Lithium brands». Drugs.com. Արխիվացված օրիգինալից 5 April 2017-ին. Վերցված է 4 April 2017-ին.
  124. 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.
  125. Wilson EN, Do Carmo S, Welikovitch LA, Hall H, Aguilar LF, Foret MK, Iulita MF, Jia DT, Marks AR, Allard S, Emmerson JT, Ducatenzeiler A, Cuello AC (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.
  126. 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.

Կաղապար:Mood stabilizers Կաղապար:Oxytocin and vasopressin receptor modulators Կաղապար:Lithium compounds Կաղապար:Elements in biology


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