Lithium Pharmacology - Medical Uses

Medical Uses

Lithium treatment is used to treat mania in bipolar disorder. Initially, lithium is often used in conjunction with antipsychotic drugs as it can take up to a month for it to have an effect. Lithium is also used as prophylaxis for depression and mania in bipolar disorder. It is sometimes used for other psychiatric disorders, such as cycloid psychosis and major depressive disorder. Lithium possesses a very important antisuicidal effect not shown in other stabilizing medications such as antiseizure drugs. Nonpsychiatric applications are limited; however, its use is well established in the prophylaxis of some headaches related to cluster headaches (trigeminal autonomic cephalgias), particularly hypnic headache. An Italian pilot study in humans conducted in 2005–06 suggested lithium may improve outcomes in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). However, a randomised, double-blind, placebo-controlled trial comparing the safety and efficacy of lithium in combination with riluzole for treatment of ALS failed to demonstrate a benefit as compared to a combination therapy over riluzole alone.

Lithium is sometimes used as an augmenting agent to increase the benefits of standard drugs used for unipolar depression. Lithium 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 (15–20 mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. To prescribe the correct dosage, the patient's entire medical history, both physical and psychological, is sometimes taken into consideration. The starting dosage of lithium should be 400–600 mg given at night and increased weekly depending on serum 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.

High doses of haloperidol, fluphenazine, or flupenthixol may be hazardous when used with lithium; irreversible toxic encephalopathy has been reported.

Lithium salts have a narrow therapeutic/toxic ratio, so should not be prescribed unless facilities for monitoring plasma concentrations are available. Patients should be carefully selected. Doses are adjusted to achieve plasma concentrations of 0.4 to 1.2 mmol Li+/l (lower end of the range for maintenance therapy and elderly patients, higher end for pediatric patients) on samples taken 12 hours after the preceding dose. Overdosage, usually with plasma concentrations over 1.5 mmol Li+/l, may be fatal, and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment, confusion, and convulsions. If these potentially hazardous signs occur, treatment should be stopped, plasma lithium concentrations redetermined, and steps taken to reverse lithium toxicity.

Lithium toxicity is compounded by sodium depletion. Concurrent use of diuretics that inhibit the uptake of sodium by the distal tubule (e.g. thiazides) is hazardous and should be avoided because this can cause increased resorption of lithium in the proximal convoluted tubule, leading to elevated, potentially toxic levels. In mild cases, withdrawal of lithium and administration of generous amounts of sodium and fluid will reverse the toxicity. Plasma concentrations in excess of 2.5 mmol Li+/l are usually associated with serious toxicity requiring emergency treatment. When toxic concentrations are reached, there may be a delay of one or two days before maximum toxicity occurs.

In long-term use, therapeutic concentrations of lithium have been thought to cause histological and functional changes in the kidney. The significance of such changes is not clear, but is of sufficient concern to discourage long-term use of lithium unless it is definitely indicated. Doctors may change a bipolar patient's medication from lithium to another mood-stabilizing drug, such as valproate (Depakote), if problems with the kidneys arise. An important potential consequence of long-term lithium use is the development of renal diabetes insipidus (inability to concentrate urine). Patients should therefore be maintained on lithium treatment after three to five years only if, on assessment, benefit persists. Conventional and sustained-release tablets are available. Preparations vary widely in bioavailability, and a change in the formulation used requires the same precautions as initiation of treatment. There are few reasons to prefer any one simple salt of lithium; the carbonate has been the more widely used, but the citrate is also available.

Lithium may be used as a treatment of seborrhoeic dermatitis (lithium gluconate 8% gel). In addition, lithium has been shown to increase production of white blood cells in the bone marrow and might be indicated in patients suffering from leukopenia.

A limited amount of evidence suggests lithium may contribute to treatment of substance abuse for some dual-disorder patients.

In 2009, Japanese researchers at Oita University reported low levels of naturally occurring lithium in drinking water supplies reduced suicide rates. A previous report had found similar data in the American state of Texas. In response, psychiatrist Peter Kramer raised the hypothetical possibility of adding lithium to drinking water as a mineral supplement rather than as a therapeutic drug. (The therapeutic dosage of lithium carbonate (tablets and capsules) or citrate (liquid) "usually ranges from 900 - 1,200 mg/day" and is adjusted according to patient response and blood levels.) This is analogous to niacin, where a low dose in multivitamin pills is taken as a vitamin supplement to prevent the niacin deficiency disease pellagra, but a high dose is prescribed as a therapeutic drug to raise high-density lipoprotein ("good" cholesterol) levels.