lithium (medication) lithium (medication) certain lithium compounds, also known as lithium salts, are used as psychiatric medication, primarily for bipolar disorder and for major depressive disorder. lithium is taken orally. lithium carbonatelithium carbonate, an example of a lithium saltclinical datatrade namesmanyahfs/drugs.commonographmedlineplusa681039license data us dailymed: lithium pregnancycategory au: d routes ofadministrationby mouth, parenteraldrug classmood stabilizeratc coden05an01 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailabilitydepends on formulationprotein bindingnonemetabolismkidneyelimination half-life24 h, 36 h (elderly)excretion>95% kidneyidentifiers iupac name lithium(1+) cas number17341-24-1pubchem cid28486drugbankdb01356chemspider26502unii8h8z5uer66chebichebi:49713chemical and physical dataformulali+molar mass6.94 g·mol−13d model (jsmol)interactive image smiles inchi inchi=1s/li/q+1key:hbbgrarxtfltsg-uhfffaoysa-n common side effects include increased urination, shakiness of the hands, and increased thirst. serious side effects include hypothyroidism, diabetes insipidus, and lithium toxicity. blood level monitoring is recommended to decrease the risk of potential toxicity. if levels become too high, diarrhea, vomiting, poor coordination, sleepiness, and ringing in the ears may occur. lithium is teratogenic, especially during the first trimester of pregnancy and at higher dosages. 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. the american academy of pediatrics lists lithium as contraindicated for pregnancy and lactation. the united states food and drug administration categorizes lithium as having positive evidence of risk for pregnancy and possible hazardous risk for lactation. lithium salts are classified as mood stabilizers. lithium's mechanism of action is not known. in the nineteenth century, lithium was used in people who had gout, epilepsy, and cancer. its use in the treatment of mental disorders began with carl lange in denmark and william alexander hammond in new york city, 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. it is on the world health organization's list of essential medicines, and is available as a generic medication. in 2020, it was the 197th most commonly prescribed medication in the united states, with more than 2 million prescriptions. it appears to be under-utilised in older people, though the reason for that is unclear. medical uses 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. it is sometimes used when other treatments are not effective in a number of other conditions, including major depression, schizophrenia, disorders of impulse control, and some psychiatric disorders in children. because the fda has not approved lithium for the treatment of other disorders, such use is off-label. 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. 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. a limited amount of evidence suggests lithium carbonate may contribute to treatment of substance use disorders for some people with bipolar disorder. schizophrenic disorders lithium is recommended for the treatment of schizophrenic disorders only after other antipsychotics have failed; it has limited effectiveness when used alone. the results of different clinical studies of the efficacy of combining lithium with antipsychotic therapy for treating schizophrenic disorders have varied. major depressive disorder lithium is widely prescribed as a treatment for depression. augmentation if therapy with antidepressants does not fully treat the symptoms of major depressive disorder (mdd) then a second augmentation agent is sometimes added to the therapy. 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. monotherapy there are a few old studies indicating efficacy of lithium for acute depression with lithium having the same efficacy as tricyclic antidepressants. 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. 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. alzheimer's disease alzheimer's disease affects forty-five million people and is the fifth leading cause of death in the 65 plus population. 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. to combat this toxic amyloid aggregation, lithium upregulates the production of neuroprotectors and neurotrophic factors, as well as it inhibits the gsk-3 enzyme. lithium also stimulates neurogenesis within the hippocampus, making it thicker. yet another cause of alzheimer's disease is the dysregulation of calcium ions within the brain. too much or too little calcium within the brain can lead to cell death. lithium is able to restore the intracellular calcium homeostasis through inhibiting the wrongful influx of calcium upstream. 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. in 2009, a study was performed by hampel and colleagues 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. 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. another study, a population study this time by kessing et al., showed a negative correlation between alzheimer's disease deaths and the presence of lithium in drinking water. areas with increased lithium in their drinking water showed less dementia overall in their population. 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. 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. 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 to 1.2 mmol li+/l 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. 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. discontinuation for patients who have achieved long term remission, it is recommended to discontinue lithium gradually and in a controlled fashion. 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. 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. adverse effects sources for the following lists. very common (> 10% incidence) adverse effects of lithium include confusion constipation (usually transient, but can persist in some) decreased memory diarrhea (usually transient, but can persist in some) dry mouth ekg changes — usually benign changes in t waves hand tremor (usually transient, but can persist in some) with an incidence of 27%. if severe, psychiatrist may lower lithium dosage, change lithium salt type or modify lithium preparation from long to short acting (despite lacking evidence for these procedures) or use pharmacological help headache hyperreflexia — overresponsive reflexes leukocytosis — elevated white blood cell count muscle weakness (usually transient, but can persist in some) myoclonus — muscle twitching nausea (usually transient) polydipsia — increased thirst polyuria — increased urination renal (kidney) toxicity which may lead to chronic kidney failure vomiting (usually transient, but can persist in some) vertigo weight gain common (1–10%) adverse effects include acne extrapyramidal side effects — movement-related problems such as muscle rigidity, parkinsonism, dystonia, etc. euthyroid goitre — i.e. the formation of a goitre despite normal thyroid functioning hypothyroidism — a deficiency of thyroid hormone. hair loss/hair thinning unknown sexual dysfunction hypoglycemia glycosuria lithium carbonate can induce a 1–2 kg of weight gain. in addition to tremors, lithium treatment appears to be a risk factor for development of parkinsonism-like symptoms, although the causal mechanism remains unknown. 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. 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. it increases the appetite and thirst ("polydypsia") and reduces the activity of thyroid hormone (hypothyroidism). 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 function, although this does not appear to be common. pregnancy and breast feeding lithium is a teratogen, causing birth defects in a small number of newborn babies. 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. 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. gabapentin and clonazepam 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 including the british national formulary. kidney damage lithium has been associated with several forms of kidney injury. it is estimated that impaired urinary concentrating ability is present in at least half of