Mechanism of action
- The exact mechanism of action of lithium is not clear, but it may block the phosphatidylinositol pathway.
- Increased plasma concentration (risks of toxicity even at therapeutic serum levels): ACEIs/ARBs; analgesics (esp NSAIDs); antidepressants (esp. SSRIs); antiepileptics; antihypertensives (methydopa; Ca channel blockers; diuretics); antipsychotics (haloperidol). NB All of these are very commonly used in the hospital and community setting.
- Antidiabetics: may impair glucose tolerance; antipsychotics: increased risk of EPSEs; parasympathomimetics (antagonistic effect)
Initiation and monitoring
- Physical exam; FBC; U&Es; TFTs; creatinine clearance; ECG; LFT all before starting.
- Initial dose should be low (400-600mg); increased weekly with monitoring up to normal dose of 800mg-1.2g (max 2g).
- Blood levels and monitoring should be taken 5 days after starting and 5 days after dose change.
- Once therapeutic dose established, monitor lithium level/U&E every 3months; TFTs 6 monthly and CC 12 monthly.
- Dose related
- Polyuria/polydipsia- effect of ADH antagonism
- Weight gain- carbohydrate metabolism effects and oedema
- Cognitive problems e.g. dulling, memory, concentration, confusion, mental slowness
- GI problems (N&V&D; dyspepsia)
- Usually requires a lower dose. Advise to take lithium with meals to avoid GI effects. Occasionally diuretics for oedema (beware interaction)
- Cardiac conduction- benign ECG change (T-wave changes; widening of QRS).
Long term effects
- 10-20% have morphological kidney change but rarely will lithium cause irreversible renal injury.
- Hypothyroidism can occur and is reversible with withdrawal of lithium. However, it can also be treated with thyroxine and is not an indication for lithium withdrawal. Note that dysthymia can be secondary to this and not always due to the bipolar disorder.
- Teratogenicity- balance risk and benefits.
- Toxic dose is defined as 1.2mmol/l- 12 hours after the drug was taken. Patients usually have symptoms >1.5mmol/l and toxicity can be fatal >2mmol/l.
- Early signs and symptoms include
- marked tremor,
- nausea and vomiting,
- diarrhoea (sometimes bloody),
- As levels rise, severe neurological complications occur: restlessness/myoclonic jerks/muscle fasciculation, chorionic movements, marked hypertonicity.
- Can progress to ataxia, dysarthria, increased lethargy, drowsiness/confusion/delirium.
- Finally, hypotension and arrhythmia signal circulatory failure and seizures/coma with permanent damage/death.
- Patient education is essential. Careful dose adjustment should always be done in patients with any problems. In late toxicity, diuresis with isotonic saline or haemodialysis (later) is used to reduce lithium levels.