Lithium is one of the most effective treatments for patients with bipolar disorder.  Its use, however, is limited by its potential for serious long-term adverse events, including renal, thyroid, and parathyroid dysfunction.

A recent study published in Lancet helps to put these various risks into perspective and indicates that women may be more vulnerable to the adverse effects of lithium than men.

This study was a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service investigating the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged > 18 years) treated with lithium. The control group consisted of age- and sex-matched cases with no lithium exposure.

After adjusting for age, sex, and diabetes, lithium treatment was associated with an increased risk of:

  • Stage 3 chronic kidney disease (HR 1.93, 95% CI 1·76–2·12; p<0·0001),
  • Hypothyroidism (2.31, 2·05–2·60; p<0·0001)

Lithium use was not associated with  hyperthyroidism.

Women were at greater risk of developing renal and thyroid dysfunction than were men, with younger women at higher risk than older women. If we look only at women taking lithium, the risk of developing renal dysfunction was 2.05-fold higher than in women with no lithium exposure.  The risk of hypothyroidism was increased by 2.37-fold.

The risk of adverse effects was greatest early on in treatment (the first 5 years). Higher lithium concentrations were associated with increased risk of all adverse outcomes.

While we are not able to prevent these adverse events,routine monitoring is essential in patients taking lithium.  This study also suggests that using the lowest effective dose of lithium may help to reduce the risk of adverse events.

Ruta Nonacs, MD PhD

Shine B, McKnight RF, Leaver L, Geddes JR.  Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data.  Lancet. 2015 May 20.