lithium (Li) chemical element of Group 1 (Ia) in the periodic table, the alkali metal group, lightest of the solid elements. The metal itself which is soft, white, and lustrous and several of its alloys and compounds are produced on an industrial scale.

The element was discovered in 1817 by Arfuedson. Since then, it has been used for treatment of gout and for salt replacement in cardiac disease, but its use was restricted due to fatal toxicity. It was rediscovered in 1949 by John Cade, for used in treatment of mania but its potential went unrecognised as it was discovered in Australia. Mogen Schou in 1957, had to rediscover it yet again before it became popular as a treatment of mania.

Lithium has traditionally been the drug of choice for the treatment of manic episode (acute phase) as well as for prevention of further episodes in bipolar mood disorder. It has also been used in treatment of depression with less success. 

There is usually a 1-2 week lag period before any appreciable response is observed. So, for treatment. of acute manic episodes, antipsychotics are usually administered along with lithium, in order to provide cover for the first few weeks.

The usual therapeutic dose range is 900-1500 mg of lithium carbonate per day. Lithium treatment needs to be closely monitored by repeated blood levels, as the difference between the therapeutic and lethal blood levels is not very wide (narrow therapeutic index).

A blood lithium level of >2.0 mEq/L is often associated with toxicity, while a level of more than 2.5-3.0 mEq/L may be lethal. Although lithium is indicated for therapeutic use in all manic episodes, the preventive use is best in usually those patients with bipolar disorder, in whom the frequency of episodes is 1-3 per year or 2-5 per two years.

The common acute toxic symptoms of lithium are neurological while the common chronic side-effects are nephrological and endocrinal (usually hypothyroidism).

The important investigations before starting lithium therapy include a complete general physical examination, full blood counts, ECG, urine routine examination (with/without 24 hour urine volume), renal function tests and thyroid function tests.

Lithium is very rapidly absorbed from the gastrointestinal tract. The peak serum levels occur between 30 minutes to 3 hours. The absorption is virtually complete in about 8 hours. The distribution is in total body water with a slow entry into the intracellular compartment. The maximum levels occur in thyroid (3-5 times serum level), saliva (two times), milk (0.3-1.0 times) and CSF (0.4 times). The steady state levels are achieved in about 7 days. There is no metabolism of lithium in the body and it is excreted almost entirely by the kidneys. Proximal reabsorption is influenced by the sodium balance, and depletion of sodium results in retention, causing higher blood levels of lithium.

Acute lithium toxicity is often associated with cardiotoxic effects, gastrointestinal symptoms, and late developing neurological signs, where as chronic forms manifest primarily as neurological symptoms including confusion, myoclonus, and seizures and carry a considerable risk of kidney diseases such as nephrogenic diabetes insipidus and tubulointerstitial nephritis.

SARS-COV-2 predominantly affects the lungs. However, recent evidence suggests it can affect the nervous, cardiovascular, gastrointestinal, and renal systems. In critically ill patients, commonly seen specific and nonspecific factors, such as mechanical ventilation, hypoxia, etc, might also contribute to injury to and functional decline of kidney. Hence, clearance of lithium, 95% of which is excreted by the kidneys, can be hampered, leading to its increased serum levels even at previously well-tolerated therapeutic doses and causing toxicity. Bipolar disorder patients on lithium maintenance therapy have been reported to come to emergency units with manifest signs of lithium toxicity after contracting COVID-19.

Published : Oct 21 2023