lithium carbonate

introduction

although lithium was first discovered to be effective in mania in 1949, by the Melbourne psychiatrist John Cade, it is still the 'gold standard' therapy.
many patients are unable to tolerate lithium and it has limited effectiveness for the depressive phase of bipolar disorders.
many patients on lithium suffer from frequent and prolonged depressive episodes, despite dramatic suppression of the periods of elevated mood.
anti-manic effect can take 6-10days
antidepressant effect is less reliable and can take 6-8wks
patients require monitoring of serum lithium levels, serum calcium (check before and during Rx as risk of hyperparathyroidism)
- monitor levels closely on initiation then every 3-12 months
- monitor U&E, TSH every 6 mths and parathyroid function annually

common initial (for 1-2 days with any increase of dosing) and usually transient effects:
- fatigue, diarrhoea, thirst, polyuria, nausea, headache, vomiting
non-compliance is common (20-50% of patients) and if lithium is abruptly discontinued, the chance of sudden relapse into mania is considerable.
the main drawbacks of lithium are the need for serum concentration monitoring, the possibility of serious toxicity, and the risk of thyroid (and less commonly renal) impairment.
increased risk of reduced urinary concentrating ability (polyuria, thirst), hypothyroidism, hyperparathyroidism, and weight gain of 1-2kg (in 5% of patients)
increased risk of diabetes insipidus in 10%
little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low¹⁾
risk of congenital malformations is uncertain, balance of risks should be considered before lithium is withdrawn during pregnancy

GIT: nausea, vomiting and diarrhoea leading to dehydration, and further toxicity due to reduced renal excretion
CNS: tremor, hyper-reflexia, ataxia, dysarthria
- these are delayed in acute toxicity as it takes time to enter the CNS
severe toxicity:
- delirium, coma, seizures
- syndrome of irreversible lithium effectuated neurotoxicity (SILENT)
  - prolonged (months-years) neurologic and neuropsychiatric symptoms following lithium toxicity despite haemodialysis
  - most commonly causes cerebellar dysfunction, and may include nystagmus, choreoathetoid movements, myopathy, blindness, extrapyramidal symptoms, brainstem dysfunction, and dementia
- prolonged prolonged QTc, bradycardia but life threatening arrhythmias are rare
- hypotension

therapeutic serum concentration for lithium is 0.8-1.2 mmol/L
a serum lithium concentration greater than 2 mmol/L is associated with severe toxicity assuming there has not been an acute overdosage
usually occurs in patients taking therapeutic doses, particularly, the elderly, where there has been either:
- a change in dose
- addition of other medications (eg non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, ACE inhibitors), or,
- decreased elimination (mild volume depletion, acute kidney injury (AKI) / acute renal failure (ARF), dehydration, chronic renal failure)
- nephrogenic diabetes insipidus due to chronic toxicity
- hypothyroidism
- hyperthyroidism
it is associated with significant morbidity and mortality
all patients with chronic toxicity should be admitted for Mx including:
- with-holding lithium doses
- 2-3L iv 0.9% saline at twice normal maintenance rates plus saline to replace GIT losses due to toxicity
- monitor U&E and serum lithium level
- fluid balance chart
- consider haemodialysis if serum level > 2.5 mmol/L
- patients with severe toxicity usually need admission to ICU

serum lithium levels correlate poorly with CNS levels in acute ingestions
symptomatic patients are admitted to a monitored setting for observation, regardless of the serum lithium concentration
manage as for acute overdosage

acute lithium poisoning < 25g rarely leads to significant toxicity due to the rapid elimination by the kidneys and slow uptake into the CNS
serum lithium levels correlate poorly with CNS levels in acute ingestions
symptomatic patients are admitted to a monitored setting for observation, regardless of the serum lithium concentration
patient is regarded as medically clear from lithium toxicity :
- when become asymptomatic and the serum lithium concentration falls below 1.5mmol/L

do not give activated charcoal as it does not bind lithium
consider whole bowel irrigation if:
- acute ingestion > 50g or more than 10-15 slow release tablets, and,
- ingestion occurred less than 2-6 hours ago, and,
- patient is alert and cooperative
send FBE, U&E and serum lithium levels (to assess serial decline as evidence of excretion)
iv 0.9% Saline reduces toxicity and increases renal excretion
- 2-3L iv 0.9% saline at twice normal maintenance rates plus saline to replace GIT losses due to toxicity
- adjust according to patient's cardiac and hydration status
- BUT BE AWARE many patients on long-term lithium therapy have diabetes insipidus, so take this into consideration when giving IV fluids as larger fluid requirements are needed to replace the increased urine output

serum lithium > 2.5 mmol/L (in chronic intake without acute overdosage)
severe effects such as delirium, seizures, coma, and/or hypotension
serum lithium > 1.5 mmol/L and despite iv saline, either:
- persistent toxicity
- inadequate urine output to ensure excretion

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