Lithium

Reasons for adding lithium

- Lithium appears to be associated with an acute antidepressant effect in up to 50% of
patients otherwise refractory to monotherapy
- In situations where single medications do not seem to have an effect, lithium has
been shown to be useful as an additional medication to treat depression
- Prophylaxis and treatment of bipolar affective disorder
- Prophylaxis of recurrent depression, especially as an adjunct in refractory depression
- As an adjunct to anti-psychotics in the treatment of schizoaffective disorder
- In the treatment of aggressive or self-mutilating behaviour

Three major issues to consider

- Caution about side effects
- Warn about lithium toxicity
- Describe lithium treatment and the need for plasma level monitoring (blood testing)

Pre-lithium work-up
- Baseline investigations of renal function
- ECG
- Thyroid function tests
o ‘Because lithium is eliminated by the kidneys, it is important to check how
well the kidneys are working by performing a renal function test before
starting any lithium therapy.’
o ‘Because lithium can interfere with thyroid function, we like to check the
thyroid before we start treatment, and then 6-monthly thereafter. We also
take a tracing of the heart to confirm that there are no pre-existing
abnormalities that may worsens with lithium treatment.’
- A concentration of 0.5-1.0mmol/L is usually sufficient for clinical effect.
- Because the dose has to be kept within certain limits, the blood has to be monitored
initially after 5 – 7 days, and then weekly until the correct level has been reached.
Finally, levels should be monitored every 3 – 6 months when stabilisation has
occurred
- Lithium is prescribed as a single dose at night

Side effects
- Tremor
- Polyuria
- Weight gain
- Nausea
- Tremor can sometimes be treated with a beta-blocker
- Nausea can be counteracted by taking the lithium with food; sometimes, changing
the preparation of lithium can make a difference
- Mention interactions with other drugs, e.g. diuretics, NSAIDs, haloperidol
Main side effects
- Early side effects of lithium are dose-related and include GI side effects (nausea,
vomiting and diarrhoea)
- Tremor (may manifest as intention tremor)
- Dry mouth
- Later side effects that are amenable to lab measurement are more numerous and
appear at higher plasma concentrations
o Check TFTs (hypothyroidism)
o Calcium, PTH – both increased (hyperparathyroidism)
o U&E (Nephrogenic diabetes insipidus)
o U&E, urine osmolality, urine sodium (Raised levels of ADH, Hypokalaemia –
arrhythmias)
o FBC (Leucocytosis, Thrombocytosis)
o Calcium (Hypercalcaemia – arrhythmias)
o eGFR, U&E, urinalysis (Nephropathy, renal failure)
o Autoantibody screen (SLE)
o Acetylcholine receptor antibodies, Tensilon test (Myasthenia gravis)

Plasma reference range of lithium

- 0.6 – 1 mmol/L

What are the signs of toxicity and how do these relate to plasma levels?
- Severe toxicity may occur at levels > 1.5mmol/L and death may occur at higher levels
(>2.0mmol/L), although toxicity has also been reported at only midly elevated serum
concentrations
- Lithium has a narrow therapeutic index and has a number of important adverse
effects in overdose, which may be fatal’ these include neurological effects (tremor,
ataxia, nystagmus, convulsions, confusion, slurred speech and coma) as well as renal
impairment

Prior to commencing lithium

- eGFR
- U&E
- Calcium
- Creatinine
- TFTs
- Full blood count

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