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Lithium in General Practice

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Adverse effects of lithium

Adverse effects are usually related to serum lithium concentrations and are infrequent at levels below 1.0 mmol/L. Mild gastrointestinal effects (mild nausea, vomiting and diarrhoea), vertigo, muscle weakness and a dazed feeling may occur initially, but frequently disappear after stabilisation. Fine hand tremors, polyuria and polydipsia (mild thirst) may persist. Mild polyuria may not be of concern but may be troublesome and the possibility of diabetes insipidus should be considered.
Skin conditions including acne, psoriasis, generalised pustular psoriasis, rashes and leg ulcers can be aggravated by lithium treatment.
Lithium has several less common but important metabolic adverse effects. Prevention and avoidance of risk factors are important keys to management (Table 1). Patients and their families/carers should be educated about early warning signs of all adverse effects, and the need for immediate advice if clinical signs of lithium toxicity such as severe or persistent diarrhoea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness occur.

Table 1 Metabolic adverse effects of lithium

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Thyroid disorders Hypothyroidism is common and is seen more frequently in women than men.5
Biochemical changes identical to those in primary hypothyroidism.
Risk factors include elevated thyroid autoantibodies or TSH at baseline, family history, middle age, high lithium concentrations.
Overt hypothyroidism is treated with thyroxine replacement. Management of subclinical hypothyroidism may be beneficial.
Hyperthyroidism reported but relatively rare.
Weight gain Significant weight gain is common and may lead to reduced compliance.6
Reported risk factors include high baseline weight, young age, female gender and concurrent antidepressants. The mechanism may involve increased intake of high calorie drinks to relieve thirst.
Weight gain or oedema should not be treated with diuretics.
Management includes counseling and dietary management. In severe cases other agents such as valproate or carbamazepine may be considered but they can also cause weight gain.
Nephrogenic diabetes
Lithium is the most common drug cause, affecting 10% of patients treated for 15 years or more.7
Risk correlates with duration of lithium treatment.
Presents as polydipsia and polyuria (24 hour urine volume > 3 L).
Dehydration, lithium intoxication and deteriorating renal function may occur and renal impairment may be permanent.
Risk factors include long term treatment, concurrent use of long term NSAIDs, chronic physical illness and increasing age.
Avoidance includes careful monitoring and awareness of risk factors. Management may include shared care with renal specialist and switch to alternative treatment.
Hyperparathyroidism Hypercalcaemia is common. Reported incidence as high as 50%. More common in women and elderly. Not linked to lithium concentrations, treatment duration or cumulative dose. May lead to renal stones, worsening psychiatric condition, dehydration and renal impairment.6
If Hypercalcaemia is mild (corrected Ca < 2.75 mmol/L) adopt a conservative approach. If clinical manifestations are present changing to another drug may be necessary.
Corrected calcium levels above 2.75 mmol/L would usually warrant discussion with a renal physician.

Avoid lithium in pregnancy

Avoid the use of lithium during pregnancy whenever possible. The overall risk of foetal malformations is 4-12% in the first trimester and therefore greater than the general population. Cardiovascular malformations include Ebstein’s anomaly, which can be detected by foetal echocardiography at 16-18 weeks gestation. Specialist review of the use of lithium (and all other mood stabilising drugs, including lamotrigine) is indicated in any woman considering becoming pregnant, and all those who have become pregnant before discontinuing mood stabilisers. The relative risk to the mother of discontinuing treatment needs to be balanced with the risks to the foetus.

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