Lithium lowers the risk of suicide in both bipolar disorder and unipolar depression, a systematic review and meta-analysis has found.

Overall, 48 randomised controlled trials, involving 6,674 participants, were included. Patients had a diagnosis of bipolar disorder (19 trials), unipolar depression (12 trials) or a mix of bipolar, unipolar or schizoaffective disorder (17 trials). They were randomised to receive either lithium, an active comparator or placebo over a period of at least three months.

When compared with placebo, lithium significantly reduced the number of suicides, odds ratio (OR) 0.13 (95% CI:0.03-0.66). There was also a significant reduction in the number of deaths from any cause,

OR 0.38 (95% CI:0.15-0.95), but no significant reduction in the number of deliberate self-harm events, OR 0.60 (95% CI:0.27-1.32).

A sensitivity analysis restricted to participants with unipolar depression also found a significant reduction in both suicide risk, OR 0.36 (95% CI:0.13-0.98) and the total number of deaths,OR 0.13 (95% CI:0.02-0.76).

When compared with active comparators, lithium tended to be better but the only significant difference was a reduction in deliberate self-harm in comparison with carbamazepine.

The wide confidence intervals reflect the small number of suicides and self-harm events. The authors suggest this may be due to the exclusion of patients at high risk of suicide from randomised trials.

Lithium may reduce the risk of suicide both by lowering the risk of relapse and by reducing aggression and impulsivity.¹

Lithium is recommended as a first-line treatment for relapse prevention in bipolar disorder.^2,3,4 In unipolar depression, it can be used to augment antidepressant treatment in patients who have not responded to switching antidepressants. Where this is effective and tolerated, long-term treatment in combination with the antidepressant is recommended.⁵

A meta-analysis found that patients with recurrent unipolar depression were 85% less likely to commit suicide if their maintenance antidepressant treatment was augmented with lithium.⁶

Nevertheless, there has been a decline in lithium use because of the need for careful monitoring, concerns about toxicity and the fact that it is dangerous in overdose. A recent meta-analysis clarified the long-term risks: there is a five-fold increase in the risk of hypothyroidism, a 10% increase in parathyroid hormone and calcium levels, a 15% reduction in urine concentrating ability with the risk of diabetes insipidus, a relatively small reduction in glomerular filtration rate and a small absolute risk of renal failure.^7,8

With careful monitoring, lithium is an effective and safe drug which should continue to be a first-line choice for long-term treatment of bipolar disorder. This meta-analysis suggests it may also have a specific role in preventing suicide in high-risk patients with bipolar disorder or recurrent depression.

Dr Phillip Bland