Lithium
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Lithium is mood stabilising drug used most commonly to treat bipolar disorder but is also used to treat mania and as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys.
Adverse effects
Monitoring of patients on lithium therapy
Contraindications
Pregnancy & breastfeeding
Lithium is teratogenic and should be avoided in pregnancy if possible (especially the first trimester). Lithium is also present in breast milk and is potentially toxic to infants.
Mechanism of action
Not fully understood, main theories are:- inhibition of cAMP formation
- inhibition of enzymes such as glycogen synthase kinase and inositol phosphatases
- modulation of glutamate receptors
Adverse effects
- nausea/vomiting, diarrhoea
- fine tremor
- nephrotoxicity: polyuria, secondary to nephrogenic diabetes insipidus
- thyroid enlargement, may lead to hypothyroidism
- ECG: T wave flattening/inversion
- weight gain
- idiopathic intracranial hypertension
Lithium toxicity
Lithium toxicity may occur due to excessive intake or impaired secretion. Several factors might lead to impairment in lithium secretion. Sodium and volume depletion due to any conditions like vomiting, diarrhoea, febrile illness, renal insufficiency, excessive exercise, water restriction, excessive sweating, low sodium diet, and congestive heart failure may enhance lithium reabsorption in the kidneys. Drugs which reduce the glomerular filtration rate might also lead to elevation of lithium levels with resulting toxicity.
Toxicity typically occurs with levels over 1.5 mmol/litre, levels over 2.0 mmol/litre are associated with significant toxicity and may need treatment with haemodialysis if neurological symptoms or renal failure are present.
Lithium toxicity features:
Severe poisoning:
Management of toxicity:
Lithium toxicity may occur due to excessive intake or impaired secretion. Several factors might lead to impairment in lithium secretion. Sodium and volume depletion due to any conditions like vomiting, diarrhoea, febrile illness, renal insufficiency, excessive exercise, water restriction, excessive sweating, low sodium diet, and congestive heart failure may enhance lithium reabsorption in the kidneys. Drugs which reduce the glomerular filtration rate might also lead to elevation of lithium levels with resulting toxicity.
Toxicity typically occurs with levels over 1.5 mmol/litre, levels over 2.0 mmol/litre are associated with significant toxicity and may need treatment with haemodialysis if neurological symptoms or renal failure are present.
Lithium toxicity features:
- nausea and vomiting
- diarrhoea
- anorexia
- apathy, lethargy and drowsiness
- ataxia
- dizziness
- lack of coordination
- muscle weakness & muscle hyper-irritability
- dysarthria
- muscle twitching and course tremor of the extremities and lower jaw
- tinnitus
- blurred vision
- choreoathetoid movements
- dysarthria
Severe poisoning:
- convulsions
- renal failure
- electrolyte imbalance
- polyuria
- hypotension (circulatory failure)
- ECG: T wave flattening/inversion
- hyper-reflexia and hyperextension of limbs
- toxic psychosis
- coma and occasionally death
Management of toxicity:
- increase fluid intake and avoid diuretics
- treatment is generally supportive with special regard to electrolyte balance, renal function, and control of convulsions.
- gastric lavage may be considered if it can be performed within 1 hour of ingesting significant quantities of lithium
- in severe toxicity haemodialysis may be considered
Monitoring of patients on lithium therapy
- inadequate monitoring of patients taking lithium is common - NICE and the National Patient Safety Agency (NPSA) have issued guidance to try and address this. As a result it is often an exam hot topic
- lithium blood level should 'normally' be checked every 3 months. Levels should be taken 12 hours post-dose
- thyroid and renal function should be checked every 6 months
- patients should be issued with an information booklet, alert card and record book
Contraindications
- Addison’s disease
- cardiac disease associated with rhythm disorder
- cardiac insufficiency
- dehydration
- personal or family history of Brugada syndrome
- low sodium diets
- untreated hypothyroidism
Pregnancy & breastfeeding
Lithium is teratogenic and should be avoided in pregnancy if possible (especially the first trimester). Lithium is also present in breast milk and is potentially toxic to infants.
Drug interactions
Because of lithiums narrow therapeutic index interactions with drugs can have a significant effect on lithium with regards to efficacy and toxicity. The key interactions are summarised in the table below:| Drug | Effects |
|---|---|
| Diuretics | Thiazide diuretics can cause a rapid increase in serum lithium levels (7–10 days) by reducing clearance of lithium. The increase in lithium levels varies from 25–400% Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity |
| NSAIDs | May increase serum lithium levels. The increase in lithium varies from 40–50%. The mechanism of this interaction is thought to be related to the effects of NSAIDs on fluid balance. This is particularly important if NSAIDs are added to a long-standing prescription of lithium |
| Haloperidol | Severe neurotoxicity has been reported with this combination |
| Carbamazepine | Has been reported to cause neurotoxic reactions |
| Dapagliflozin | Concomitant administration with may decrease serum lithium levels due to an increase in lithium renal clearance |
| Antidepressants with a serotonergic action (includes SSRIs, tricyclic antidepressants, venlafaxine & duloxetine) | Have rarely been linked to an increased incidence of central nervous system toxicity when used with lithium |
| ACE inhibitors | Decrease the excretion of lithium. They can precipitate renal failure. If these two drugs are prescribed together, extra care is required in monitoring both serum creatinine and lithium levels |
| Drugs that prolong the QT-interval | Potential for additive effects when co-administered |
| Drugs that cause hypokalaemia | Potentially increased risk of torsade de points when co-administered |
Lithium key points
- Lithium has a narrow therapeutic index and serum levels should be taken at 12 hours post dose.
- Serum levels should be between 0.4-1 mmol/litre.
- Toxicity typically occurs with levels over 1.5 mmol/litre, levels over 2.0 mmol/litre are associated with severe poisoning and warrant urgent treatment.
- Patients should carry lithium cards to alert medical professionals of treatment and to monitor levels. Monitoring should normally occur every 3 months