The most effective long-term treatment for bipolar disorder is lithium. It offers protection against depression and mania and reduces the risk of suicide and short-term mortality. However, according to a study in The Lancet ,safety concerns have made the use of lithium controversial.

The authors examined about 400 articles to research the possible adverse effects of lithium and found abnormalities in the thyroid and parathyroid in about 25% of patients who receive lithium therapy, compared with 3% and 0.1% in the general population. They also observed that lithium causes weight gain and has the potential to slightly reduce the kidney's ability to concentrate urine.

They highlight that evidence of lithium treatment being associated with congenital abnormalities in pregnancy is still uncertain, and there is very little proof that links lithium to skin problems or hair loss.

The authors recommend that patients should discuss the risks of adverse events with their physicians before starting lithium treatment, and also suggest having a serum calcium test to baseline blood tests due to the high risk of hyperparathyroidism. They also state that the effects of lithium in pregnancy are uncertain and need more evidence, and therefore newly recommend explaining the uncertainty about risk of congenital malformations to women of childbearing age contemplating lithium treatment, instead of considering lithium as a contraindication, saying:

"Women who would like to conceive or have become pregnant while receiving lithium should be advised that the increased risk of congenital malformations is uncertain; patient and clinician should discuss the balance of risks between harm to the baby and maternal mood instability before making a decision to stop lithium therapy."

They continue saying that more research is also required to clarify the link between lithium, calcium, and the kidneys and suggest that those currently undergoing lithium therapy should have 12-monthly or sooner repeat tests of renal, parathyroid, and thyroid function. The tests should be conducted even more frequently, should an abnormal result be found or the patient has a family history of endocrine disease.

They also recommend to immediately repeat blood tests in patients with changes in mood state, for instance mania and suggest to routinely record any events of adverse effects, including skin and hair disorders, so that these can be added to the existing body of evidence.

The authors highlight that overdosing of lithium is dangerous, and so is taking lithium under circumstances affecting sodium or blood volume depletion. They point out that this occurs in the majority of patients who experience lithium toxicity when they are ill with diarrhea, vomiting, heart failure, renal failure, at times of surgery, or secondary to a drug interaction, for example with non-steroidal anti-inflammatory drugs and angiotensin-converting-enzyme [ACE] inhibitors.

They conclude:

"Evidence has confirmed the important therapeutic benefits of lithium relative to some of the alternative drugs that have replaced it, which might lead to wider use of lithium. Clinical practice guidelines have long recommended lithium as a first-line long-term treatment for bipolar disorder but its use has decreased, partly because of safety concerns...This review provides a comprehensive synthesis of the evidence of harm that should inform clinical decisions and draw attention to key questions in urgent need of further clarification."

Australian doctors Dr Gin S Malhi at the University of Sydney, NSW and Dr Michael Berk at the University of Melbourne, VIC, declare in a linked comment:

"In the context of efficacy data that have upgraded the ranking of lithium, and in conjunction with new data that recalibrate the safety risks of alternative drugs, 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."

Written by Petra Rattue