What is lithium?

Since the 1960s, lithium has become a mainstay of treatment for bipolar disorders. It has been recommended for both the treatment of acute mania and for the augmentation of antidepressants in depression, although its effectiveness as an antidepressant when used alone has been disputed.

What is the evidence for lithium as a treatment for bipolar disorder?


Moderate to high quality evidence suggests medium-sized effects of greater improvement in acute mania symptoms with lithium than with placebo or topiramate, although there was a large effect of greater improvement in acute mania symptoms with tamoxefin than with lithium. No benefit was found for depression severity or for response to treatment for lithium over placebo or quetiapine, and no differences between groups were found for rates of switching to mania. Lithium was more likely than placebo to cause tremor and somnolence.

Moderate quality evidence finds small to medium-sized effects for the following predictors of lithium response (in order of descending effect size): a mania-depression sequence rather than a depression-mania sequence, no rapid cycling, having a family history of bipolar disorder, low body mass index, no psychotic symptoms, fewer mood episodes prior to lithium treatment, shorter prelithium illness duration, and later age of onset of bipolar disorder. Having a family history of lithium response and fewer hospitalisations prior to lithium treatment may also predict lithium response.

Relapse prevention

Moderate to high quality evidence suggests a small to medium-sized benefit of lithium for preventing relapse to mania when compared to placebo, carbamazepine, lamotrigine or valproate. There may also be some benefit for preventing relapse to depression when lithium is compared to placebo.

Moderate quality evidence suggests lithium + valproate, lithium + imipramine, or lithium + oxcarbazepine may be more effective than placebo for any relapse prevention (small to medium-sized effects). Placebo however, was better tolerated than lithium or lithium + valproate. There were fewer relapses with lithium with or without additional valproate or oxcarbazepine, than with imipramine.

Other outcomes

Moderate to high quality evidence suggests self-harm, but not suicide, may be reduced with lithium use when compared to placebo or carbamazepine, with no differences when compared to lamotrigine, olanzapine, divalproex, or quetapine. There may be an association between increased levels of lithium in drinking water and reduced rates of suicide in the community.

Lithium is unlikely to elevate prolactin levels or cause cutaneous adverse reactions, but serum creatinine levels may increase slightly.

July 2020

Last updated at: 4:05 am, 8th July 2020
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