Lithium tends to make existing skin conditions worse, especially acne and psoriasis.

Lithium is a naturally occurring metallic element whose antimanic properties were discovered by the Australian psychiatrist, John Cade, in 1949.

Bipolar disorder is often misdiagnosed as unipolar depression.

Subsequently, lithium has been found to have prophylactic effects in bipolar disorder and has revolutionised the treatment of this illness. Lithium also has prophylactic effects in recurrent depressive and schizoaffective disorder. It is available commercially as the carbonate salt.

Lithium is the mainstay of treatment in bipolar disorder. Although an effective antimanic agent, this effect is delayed 7-14 days after first commencing treatment, hence an antipsychotic drug (such as haloperidol) is used in the acute phase of mania or hypomania. Once the acute phase is settled, maintenance lithium treatment is usually preferred.

About 90% of individuals who are experiencing their first manic episode will subsequently suffer recurrences of mania and/or depression.

Therefore, most individuals will need ongoing prophylaxis with mood stabilisers. Lithium reduces the frequency and severity of recurrences in the majority of cases, with about one in five people who are taking lithium remaining free of illness as long as they continue to take this medication.

For many people, lithium by itself does not seem to be an effective antidepressant, and in the depressive phase of bipolar disorder, co-administration of antidepressants is usually needed.

In non-bipolar depressive illness (i.e., major depression), lithium can be used in two ways.

Firstly, it can be used to augment the effect of antidepressants (especially tricyclics) when the antidepressants alone are ineffective - this method is often successful.

Secondly, lithium can be used prophylactically in recurrent depressive illness where its effectiveness is similar to tricyclics. In prophylaxis for recurrent depression, either lithium or antidepressants are used, there being no advantage in this situation for the combination of both over either drug alone.

Psychiatric uses

• Acute treatment of mania or hypomania in bipolar disorder
• Prophylaxis in bipolar disorder and schizoaffective disorder
• Prophylaxis in recurrent depressive illness
• Augmentation of antidepressants in acute depressive illness
• Treatment of depression in bipolar disorder

The correct dosage of lithium is determined for each individual by a blood test which measures the serum lithium concentration. The therapeutic range for serum lithium is between 0.6-1.2 mmol/L but increasingly conservative levels are being used. For prophylaxis in bipolar disorder, most clinicians prefer a serum level of about 0.6-0.8 mmol/L. Some individuals need higher levels but these levels carry a higher risk of adverse effects. Symptoms of lithium toxicity rarely appear at levels below 1.2 mmol/L but are common above 2 mmol/L. Serum lithium levels vary, being high soon after a dose is taken, and then falling until the next dose is taken. The therapeutic range is standardised at 12 hours after the last dose, and all figures given here apply to blood lithium levels measured at 12 hours.

For the acute treatment of mania, the usual dosage of lithium that produces blood levels within the desired range is from 500-2000 mg given in divided doses 2-3 times per day. Lower doses are given in the elderly and in people with impaired kidney function. If serum levels are low with doses above 1500 mg/day, possible reasons include poor adherence, impaired absorption (e.g., antacids) or more commonly nephrogenic diabetes insipidus (see side effects). However, some individuals who metabolise lithium quickly do require high dose levels.

Measuring lithium serum levels.

The serum lithium levels needs to be checked at 5-7 day intervals at the beginning of treatment and the dose adjusted accordingly until stable levels in the desired range are achieved, usually after 2-3 weeks. Thereafter the level is checked monthly for 2-3 months, then maintenance checks would continue every 3-4 months while the individual remains on lithium, or more frequently if the level is not stable. When measuring lithium levels, the following requirements apply:

• 12 hours have elapsed since the last tablet.
• The lithium is taken in a divided dose (morning and evening).
• The lithium has been taken for at least 5-7 days to ensure a steady state dosage.
• The individual has adhered to the prescribed dose and the time of administration.

Individuals need to be instructed that on the morning of their blood test they should not take their lithium until after the sample has been taken to measure the trough level, otherwise an incorrect high level will result. If they forget to take their lithium they should never take extra tablets to make up for the missed dose, but simply take the next due dose.

Common side effects

• Nausea and diarrhoea - these symptoms are common in the first few weeks and usually settle. If symptoms persist then taking smaller doses more often may help (e.g., 250 mg q.i.d. (four times daily) instead of 500 mg b.d. (twice daily)). If these symptoms appear after treatment is established, they may indicate toxicity (see following page).
• Metallic taste in the mouth
• Weight gain
• Difficulty concentrating (usually mild)
• Increased thirst and drinking more fluid than usual

Less common side effects

• Acne - lithium tends to make existing skin conditions worse, especially acne and psoriasis.
• Tremor - can be treated with propranolol tablets.
• Hypothyroidism - lithium substitutes with iodine and can interfere with the ability of the thyroid gland to produce thyroid hormone. This interference can be corrected by giving thyroxine and is reversible on stopping lithium.
• Lithium can disturb the control of diabetes in individuals taking insulin, and insulin dosage may need adjustment.
• Increased urine output and increased thirst - most people taking lithium notice that they drink more fluid and pass more urine than usual, although the increase is only modest. When this increase becomes severe, it indicates that the kidneys are unable to concentrate the urine properly. This effect is reversible and does not mean the kidneys are damaged. A simple indicator is the number of times at night the person has to pass urine. If urine is passed regularly two or more times each night, the individual may have diabetes insipidus. This side effect can be reversed by appropriate treatment and should be reported to the treating doctor.

Lithium toxicity.

When the blood level of lithium becomes too high, toxicity can occur. At very high levels, toxicity can cause convulsions, acute renal failure, coma and death.

This outcome is rare and can be prevented by a few simple precautions. Dangerous lithium toxicity only occurs if early symptoms of toxicity are ignored, hence, education for the individual is very important.

The most common cause of toxicity and increased side effects is dehydration, which is most likely to occur with hot weather and physical exertion causing loss of fluid from sweating.

Other causes are accidental overdose, urinary tract infection, gastroenteritis with vomiting and diarrhoea, kidney disease, and some drugs which reduce the rate lithium is cleared from the body (e.g., thiazide diuretics, some anti-inflammatory drugs or NSAIDS).

Early symptoms of lithium toxicity are:

• Nausea
• Vomiting
• Diarrhoea
• Unsteadiness
• Forgetfulness/mild confusion

If these symptoms persist for over 24 hours, manage as for possible lithium toxicity.

More severe lithium toxicity causes:

• Severe tremor
• Dysarthria (slurring or imperfect articulation of speech)
• Ataxia (unsteadiness on the feet)
• Confusion/coma
• Abdominal cramps
• Renal failure

If the above symptoms are ignored, the individual's condition may progress to seizures and coma.

Lithium Precautions

• A range of tests need to be conducted before lithium treatment is started. These include thyroid function tests, kidney function tests, and ECG. It is important to establish a baseline against which later check-ups can be compared. Once a maintenance dose of lithium is determined, thyroid function tests are usually done every 6-12 months, while kidney function tests and electrolytes are usually monitored every 3 months.
• Lithium may have adverse interactions or cause lithium toxicity if taken with other medications such as non-steroidal anti-inflammatory drugs (NSAIDs), thiazide diuretics, and other drugs. Individuals are advised to talk to their doctor or pharmacist before taking any other medications.

Lithium During Pregnancy

• Lithium enters the foetal circulatory system if taken during pregnancy. This drug rarely causes a tricuspid valve deformity and can also impair thyroid function of the new-born infant. Additionally, lithium is excreted in breast milk so bottle-feeding is recommended. Even so, in severe disease, patients may elect to continue with lithium throughout pregnancy.