Lithium Flashcards
Signs of intoxication require treatment withdrawal. What are the signs of lithium overdose?
- Increasing GI disturbances (e.g. vomitting, diarrhoea)
- Visual disturbances
- Polyuria
- Muscle weakness
- Fine tremor, increasing to coarse tremor
- CNS disturbances (e.g. confusion, drowsiness, stupor, lack of coordination)
- Abnormal reflexes
- Myoclonus (involuntary twitching/jerking of muscles)
- Incontinence
- Hypernatraemia
What are signs of severe lithium overdose?
- Seizures
- Cardiac arrhythmias (including sinoatrial block, bradycardia, 1st degree heart block)
- BP changes (hypotension)
- Circulatory failure
- Renal failure
- Coma
- Sudden death
Most common reason for lithium intoxication
- Most often due to complication of long term lithium therapy, caused by reduced excretion of the drug
Factors that cause reduced excretion of lithium
- Dehydration
- Reduced renal function
- Infection
- Co-administration of drugs that interact e.g. diuretics and NSAIDs
Why might you get delayed onset of symptoms (12 hours or more) with acute deliberate overdose?
- Due to slow entry of lithium into tissues and continuing absorption from MR forms
What is the therapeutic serum-lithium concentration range?
0.4-1mmol/litre
Which concentration of serum-lithium is associated with serious toxicity? What might treatment consist of?
More than 2mmol/litre
May require haemodialysis if neurological symptoms or renal failure
Why should lithium be prescribed by brand
Preparations can vary widely in bioavailability
What are the two lithium salts available
Lithium carbonate & lithium citrate
They are NOT dose equivalent
How to manage acute overdose
- High serum-lithium concentrations may be present without features of toxicity
- Usually just need to take measures to increase urine output (e.g. increase fluid intake but AVOID diuretics)
- Otherwise, give supportive treatment and consider electrolyte balance, renal function, control of convulsions
- Consider gastric lavage if appropriate
- Consider whole-bowel irrigation for significant ingestion
When is gastric lavage appropriate in managing acute overdose
Consider it if it can be performed within 1 hour of ingesting significant quantities of lithium
Use of lithium salts in pregnancy
- Avoid if possible, esp in 1st trimester (teratogenic risk including cardiac abnormalities)
- Dose requirements increased during 2nd and 3rd trimester
- Return abruptly to normal dose on delivery of baby
- Close monitoring of serum-lithium concentration as risk of toxicity in neonate
Use of lithium salts when breastfeeding
Avoid - present in milk & risk of toxicity in infant
Use of lithium salts in renal impairment
Use with caution in mild-moderate impairment
Avoid in severe impairment
How many hours post-dose should serum lithium concentrations be taken?
12 hours
What is the serum lithium concentration that should be achieved, including the range for maintenance therapy & for elderly patients
0.4-1mmol/litre
Lower range of this for elderly & maintenance therapy
What is the target serum lithium concentration that is recommended for acute episodes of mania & for patients who have previously relapsed or who have sub-syndromal symptoms
0.8-1mmol/litre
How often should serum lithium concentrations be taken
Weekly after initiation, and after each dose change until concentrations are stable
Then every 3 months for the 1st year
Then every 6 months thereafter
In which cases should serum lithium concentration be taken every 3 months?
65 and over
Taking drugs that interact (e.g. NSAIDs)
At risk of impaired renal or thyroid function
Increased calcium levels or other complications
Poor symptom control
Poor adherence
Last serum lithium conc was 0.8mmol/L or higher
When should additional measurements of serum lithium concentrations be taken
If pt developed significant intercurrent disease
Or if there is a significant change in pt sodium or fluid intake
Why is abrupt withdrawal of lithium not recommended?
What should you consider prescribing if lithium is to be stopped abruptly?
Increased risk of relapse
If stopped or discontinued abruptly, consider changing to atypical antipsychotic or valproate
If lithium is stopped, the dose should be gradually decreased over a period of….
At least 4 weeks
Preferably up to 3 months
Does treatment cessation cause withdrawal or rebound psychosis?
No clear evidence of this. However stopping lithium abrupt increases the risk of relapse
Lithium: important interactions with drugs that alter renal function e.g.
ACEi
ARBs
NSAIDs
Diuretics
Can lithium be taken with ACEi e.g. ramipril, enalapril, perindopril
Severe interaction: predicted to increase concentration of lithium; monitor and adjust dose
Also increases risk of nephrotoxicity
Can lithium be taken with ARBs e.g. candesartan, olmesartan, losartan, valsartan
Severe Interaction: potentially increased conc of lithium; monitor conc and adjust dose
Can lithium be taken with NSAIDs e.g. naproxen, ketoprofen, meloxicam, celecoxib?
Severe interaction: increased conc of lithium; monitor conc and adjust dose
Can lithium be taken with diuretics e.g. chlortalidone, eplerenone, indapamide, bendroflumethiazide, metolazone, spironolactone, furosemide
Severe interaction: increases conc of lithium; monitor conc and adjust dose
Can lithium be taken with serotonergic drugs e.g. MAOis, SSR agonists like almotriptan, citalopram, fluoxetine, dexamfetamine, fentanyl, ondansetron?
AVOID - increased risk of serotonin syndrome
Can lithium be taken with TCAs e.g. lofepramine, amitriptyline, nortriptyline, clomipramine, dosulepin?
Use with caution - increased risk of neurotoxicity
Can lithium be taken with methotrexate
Increased risk of nephrotoxicity - but no recommendations, so can be used
Which class of antibiotics should be avoided, or the dose adjusted, in patients taking lithium? What is the interaction?
- The tetracyclines e.g. oxytetracycline, lymecycline, doxycycline, minocycline
- Increased risk of lithium toxicity
Which antibiotics interact severely with lithium (one class of abx + one type)
Tetracyclines - increased risk of lithium toxicity. Avoid or adjust dose.
Metronidazole - increased conc of lithium. Avoid or adjust dose.
Indications for lithium
- Treatment and prophylaxis of:
○ Mania
○ Bipolar disorder
○ Recurrent depression
○ Aggressive or self-harming behaviour
Dose of lithium
- Adjusted according to serum-lithium concentration
- Doses initially divided throughout the day
- Once daily administration is preferred when serum-lithium concentration is stabilised
Lithium is contraindicated in
Addison’s disease
Cardiac disease associated with rhythm disorder
Cardiac insufficiency
Dehydration
FHx or PHx Brugada syndrome
Low sodium diet
Untreated hypothyroidism
Caution for lithium salts in long term use
○ Associated with thyroid diseases and mild cognitive & memory impairment
○ Only undertake with careful assessment of risk and benefit
○ Monitor thyroid function every 6 months (more often if evidence of deterioration)
○ Need for continued therapy should be assessed regularly and pt should be maintained after 3-5 years only if benefit persists
Patient and carer advice for all pt on lithium salts
- Report any signs and symptoms of lithium toxicity, hypothyroidism, renal dysfunction (e.g. polyuria, polydipsia) and benign intracranial hypertension (persistent headache and visual disturbance)
- Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake
- Lithium treatment packs on initiation (PIL, lithium alert card, record book for serum-lithium conc)
- May impair performance of skilled tasks e.g. driving and operating machinery
Monitoring of pt parameters
- Assess renal, cardiac and thyroid function before treatment initiation
ECG recommended if CVD or risk factors for it - Body weight/BMI, serum electrolytes, eGFR and thyroid function every 6 months during treatment (more often if evidence of impaired renal/thyroid function or raised calcium levels)
- Monitor cardiac function regularly
Cautions for lithium
- Avoid abrupt withdrawal (risk of relapse)
- Cardiac disease
- Concurrent ECT (may lower seizure threshold)
- Diuretic treatment (risk of toxicity)
- Elderly (reduce dose)
- Epilepsy (may lower seizure threshold)
- Myasthenia Gravis
- Psoriasis (risk exacerbation)
- QT interval prolongation
- Review dose as necessary in diarrhoea, vomiting, and intercurrent infection (esp if sweating profusely)
- Surgery
- Long term use
