Lithium remains best for bipolar

Doctors should feel more confident in recommending lithium for people with bipolar disorder, say Oxford University researchers who have reviewed the evidence on possible side-effects of the drug.

Lithium is the most effective long-term therapy for bipolar disorder, but its use has decreased. This is partly due to concerns about the drug’s safety, such as its possible effect on kidney function.

Since many patients who might benefit from lithium may be missing out because of these uncertainties, the Oxford team led by Professor John Geddes of the Department of Psychiatry set out to gather better information about lithium’s side-effects.

They assessed almost 400 articles investigating the possible adverse effects of lithium and make a number of recommendations to guide lithium treatment in the future. The results are published in the Lancet medical journal.

Professor Geddes and colleagues conclude there is an increased risk of abnormalities in the thyroid and parathyroid glands. These occur in about 25% of patients on lithium therapy compared with 3% and 0.1% in the general population, respectively.

Lithium treatment also causes weight gain, and can slightly reduce the ability of the kidneys to concentrate urine.

However, the researchers found that evidence linking birth defects with lithium treatment in pregnancy remains uncertain, and there is very little evidence linking lithium with skin problems or hair loss.

Bipolar disorder is relatively common and can occur at any age. It is estimated to affect around one person in 100.

People with bipolar disorder can experience moods that swing from one extreme to another, having periods of depression and mania lasting for several weeks or longer. These phases of feeling high and low are often so extreme that they interfere with everyday life. 

Lithium has been shown to protect against both depression and mania, and reduce the risk of suicide.

The researchers say the risks of side-effects should be discussed with the patient prior to starting lithium treatment. They recommend adding tests of calcium levels to blood tests in view of the high risk of hyperparathyroidism.

The team also suggests that the uncertainty surrounding risk of birth defects should be explained to women of childbearing age contemplating lithium treatment, rather than simply not recommending lithium during pregnancy.

Professor Geddes and colleagues say that more research is needed on the relationship between lithium and the kidney.

For people currently taking lithium, they recommend that tests of renal, parathyroid and thyroid function should be repeated at least every 12 months. Blood tests should be repeated if there is a change in mood state.

The researchers add that lithium is dangerous in overdose, or under circumstances that can lead to depletion of sodium levels or blood volume. They note that most patients who experience lithium toxicity do so when ill, for example with diarrhoea, vomiting, heart failure, renal failure, or surgery – or through interaction with another drug they are taking.

'This study provides timely clarification of the toxicity associated with lithium therapy and, on balance, reaffirms its role as a treatment of choice for bipolar disorder,' comment Dr Gin Malhi of the University of Sydney and Dr Michael Berk of the University of Melbourne in a related article in the Lancet.

The research was funded by the UK National Institute for Health Research.

Source: The Lancet