14th February 2025

Lithium

Lithium is the gold standard for long-term management of bipolar disorder. However, it has a narrow therapeutic window and is associated with several significant adverse effects.

It can also be used to augment the effects of antidepressants in treatment-resistant depression.

Lithium monitoring and target levels

Prior to starting lithium, BMI, FBC, U&Es, calcium, and TFTs are required in all patients. An ECG is required for patients with cardiovascular disease or those at high risk. Whilst on treatment, BMI, U&Es, calcium, and TFTs need to be monitored every 6 months (more frequently if abnormal).

Lithium levels must be checked 5 days after starting or changing the dose (12 hours post-dose). Once established, levels should be checked every 3 months for the first year, and 6 monthly thereafter, or 3 monthly for patients over 65, those taking interacting medications, with impaired renal or thyroid function, or with poor adherence.

Adverse effects of lithium

Short-term adverse effects include polyuria and polydipsia (due to ADH antagonism leading to nephrogenic diabetes insipidus), weight gain, cognitive impairment, fine tremor, GI upset and benign leucocytosis. Benign ECG changes or exacerbation of existing arrhythmias may occur.

Long-term adverse effects include renal impairment, hyperparathyroidism (and thus hypercalcaemia) and hypothyroidism.

Lithium is teratogenic; it is classically associated with Ebstein’s anomaly of the tricuspid valve.

Drug interactions with lithium

Drug interactions can rapidly lead to toxicity or reduced efficacy (and relapse).

ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, and diuretics are important and common causes of increased plasma concentration, due to lithium being excreted wholly renally in an unchanged form. Antacids and theophylline can decrease the plasma concentration.

When given with amiodarone, it increases the risk of hypothyroidism.

Lithium toxicity

Early clinical features include coarse tremor, anorexia, nausea and vomiting, diarrhoea and fatigue. As the level increases, severe complications develop such as myoclonus, hypertonia, drowsiness, confusion, cardiovascular collapse, seizures and coma. Neurological damage may be permanent.

Lithium toxicity requires urgent IV isotonic saline and possibly haemodialysis.