Mood Stabilisers: Lithium

Question 1

What is the role of mood stabilisers?

Answer 1

Mood stabilisers are drugs that are used to prevent depression and mania in bipolar affective disorder and schizoaffective disorder.

Question 2

What drugs are used to treat an acute severe manic episode?

Answer 2

Atypical antipsychotics have a rapid onset of action compared to the mood stabilisers and so can be used in an acute severe manic episode.

Question 3

Briefly describe the treatment of acute mania or hypomania

Answer 3

Question 4

What are the indications of lithium?

Answer 4

First-line prophylaxis in bipolar affective disorder. Also effective in an acute manic episode (if an atypical antipsychotic is ineffective) and as an adjunctive treatment for depression (to prevent antidepressant-induced hypomania).

Question 5

What is the mechanism of action of lithium?

Answer 5

Lithium is an element in the body that is handled in a similar way to sodium. There is some evidence that bipolar patients have an ↑ intracellular concentration of sodium and calcium, and that lithium can ↓ these. With lithium, a decreased activity of sodium-dependent intracellular secondary messenger systems has been shown, as well as modulation of dopamine and serotonin neurotransmitter pathways, ↓ activity of protein kinase C and ↓ turnover of arachidonic acid. Lithium may also have neuroprotective effects mediated through its effects on N-methyl-D-aspartate (NMDA).

Question 6

What are the side effects of lithium?

Note: GI and LITHIUM

Answer 6

• GI disturbances
• Leucocytosis
• Impaired renal function
• Tremor (fine) / teratogenic
• Thirst (polydipsia)
• Hypothyroidism/hair loss
• Increased weight and fluid retention
• Urine ↑ (polyuria)
• Metallic taste

Question 7

What are the sights and symptoms of lithium toxicity?

Note: TOXIC

Answer 7

• Tremor (coarse)
• Oliguric renal failure
• AtaXia
• Increased reflexes
• Convulsions/ coma/ consciousness ↓

Note: normal therapeutic levels of lithium are 0.4– 1.0 mmol/L. Toxic levels are >1.5 mmol/L (lithium has a narrow therapeutic window).

Question 8

What are the contraindications and cautions of lithium?

Answer 8

Avoid in renal failure, pregnancy (teratogenic) and breast feeding .

Caution with QT prolongation (including concomitant use of drugs that ↑ QT interval), epilepsy ( ↓ seizure threshold), diuretic therapy.

Lithium is contraindicated in untreated hypothyroidism, Addison’s disease and Brugada syndrome (heart disease with ↑ risk of sudden cardiac death).

Question 9

Briefly describe the monitoring of lithium therapy

Answer 9

Before lithium treatment is started U&Es and eGFR (lithium has renal excretion and is nephrotoxic), TFTs , pregnancy status and baseline ECG should be checked. Drug levels should be closely monitored and patients should be informed of potential side effects and toxicity.

Lithium levels should be monitored 12 hours following the first dose, then weekly until therapeutic level (0.4– 1.0 mmol/L ) has been stable for 4 weeks. Once stable check every 3 months .

U&Es should be checked every 6 months.

TFTs should be checked every 12 months.

Question 10

Briefly describe the dosing of lithium and the ideal lithium level

Answer 10

Usually given as lithium carbonate. Must be given for at least 18 months for clear benefit. Starting dose 400 mg at night. Titrate dose (400– 1200 mg/day ) to keep plasma levels between 0.5 and 1.0 mmol/L.

Question 11

What is the route of administration for lithium?

Answer 11

Oral.

Question 12

What are the DO’s when prescribing lithium?

Answer 12

Check lithium levels (12 hours post dose), at least every three months and during any intercurrent illness (can ↑ causing toxicity).

At each consultation, ask about any signs of toxicity or signs of hypothyroidism.

Check thyroid function, U&Es, calcium and creatinine every 6– 12 months.

Inform patients: of potential toxicity and symptoms of this; the need for contraceptives in women of child bearing age; the need for regular fluid intake; the need for compliance in taking medication; of the dangers of crash diets; to avoid NSAIDs; not to exceed more than 1– 2 units of alcohol per day; that it takes 3– 6 months to be established on lithium and that lithium cards are available from pharmacists.

Question 13

What are the DON’Ts when prescribing lithium?

Answer 13

Prescribe if you are not a specialist.

Give lithium to women of child bearing age. Lithium is teratogenic and can cause congenital heart defects.

Give in severe renal failure.

Prescribe NSAIDs, diuretics (particularly thiazides) or ACE inhibitors without careful thought.

Prescribe lithium if you feel that adherence to treatment will be a problem.

Withdraw lithium abruptly. Abrupt withdrawal (either because of poor compliance or rapid change in dose) can precipitate relapse. Withdraw lithium slowly over several weeks, monitoring for signs of relapse.

Question 14

How is lithium toxicity managed?

Answer 14

Lithium toxicity is a medical emergency which can lead to seizures, coma and death.

Lithium toxicity is enhanced by the 4 D ’s:

• Dehydration
• Drugs (ACE inhibitors, NSAIDs)
• Diuretics (thiazide)
• Depletion of sodium

If signs of toxicity are identified, lithium should be stopped immediately.

A high intake of fluid should be provided including intravenous sodium chloride therapy, to stimulate osmotic diuresis. In the most severe cases, renal dialysis may be needed.