Lithium for maintenance treatment of bipolar disorders
Brief summary
Evidence from systematic reviews
What is the current evidence for the use of lithium in the maintenance treatment of bipolar disorders?
Lithium performs better than placebo or carbamazepine in preventing relapses of bipolar disorder. The inconclusive results of one trial favoured valproate when compared to lithium in the prevention of bipolar relapses. In the single study of olanzapine, olanzapine performed better in the prevention of all relapses and relapse of manic episodes, while lithium performed better in the prevention of depressive episodes.
All results tended to favour lithium when compared to imipramine, except in the prevention of depressive episodes of bipolar disorders. In comparison with lamotrigine, lithium tended to prevent manic episodes, and lamotrigine tended to prevent depressive episodes. Lithium was compared to a combination of lithium and imipramine in three small studies with inconclusive results, and based on scarce data. They tended to favour lithium instead of the combination of lithium and imipramine.
Eleven of the 25 studies were sponsored by pharmaceutical industry.
Is there any group of patients that respond better to lithium than the others?
Primary studies included adult patients, although one study analysed children. Patients with substance abuse within the last 3 months or serious risk of suicide were excluded in most primary studies. Patients with rapid cycling were excluded from 17 of the 25 included trials. Patients were mostly stabilised after an acute episode and treated as outpatients.
Should lithium be used as a single or combination treatment?
As a single treatment, lithium performed better than placebo, carbamazepine, and imipramine (except in the prevention of depressive episodes). Lithium performed better than olanzapine in the prevention of depressive episodes. In comparison with lamotrigine, lithium tended to prevent manic episodes, and lamotrigine tended to prevent depressive episodes.
As a combination treatment, three small studies compared lithium to a combination of lithium and imipramine, and they tended to favour lithium instead of the combination. Three other studies compared lithium with a combination of lithium and flupenthixol, or lithium and amytriptyline, or lithium and valproate, but they were of poor quality and so cannot offer conclusive evidence.
What are the adverse events at short and long term?
Although patients on the primary studies were followed up to 2.5 years, most of them failed to provide the necessary information about relevant adverse events, such as, weight gain, motor disorders and suicide attempts.
For how long should lithium (single or combination) be used?
Trials used lithium for up to 2.5 years.
Is lithium more efficacious than other mood stabilisers in the maintenance treatment of bipolar disorders?
As a single treatment, lithium performed better than placebo, carbamazepine, and imipramine (except in the prevention of depressive episodes). Lithium performed better than olanzapine in the prevention of depressive episodes. In comparison with lamotrigine, lithium tended to prevent manic episodes, and lamotrigine tended to prevent depressive episodes.
Is the balance between harm and benefit favourable to the use of lithium?
It is not clear from the trials whether the adverse events observed are maintained in the long term.
What type of research (if any) is needed to clarify the benefits and harms of using lithium in the treatment of acute mania?
Trials performed in heterogeneous populations (including those with substance abuse), regardless of risk of suicide, measuring relevant clinical outcomes, representing both benefit and harm. Trials should compare a combination of lithium, other mood stabilisers (e.g., valproate, carbamazepine), and olanzapine with single drugs.
