Lithium treatment for unipolar major depressive disorder: Systematic review

<jats:sec><jats:title>Background:</jats:title><jats:p> The potential value of lithium treatment in particular aspects of unipolar major depressive disorder remains uncertain. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> With reports of controlled trials identified by systematic searching of Medline, Cochrane Library, and PsycINFO literature databases, we summarized responses with lithium and controls followed by selective random-effects meta-analyses. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We identified 36 reports with 39 randomized controlled trials: six for monotherapy and 12 for adding lithium to antidepressants for acute major depression, and 21 for long-term treatment. Data for monotherapy of acute depression were few and inconclusive. As an adjunct to antidepressants, lithium was much more effective than placebo ( p&lt;0.0001). For long-term maintenance treatment, lithium was more effective than placebo in monotherapy ( p=0.011) and to supplement antidepressants ( p=0.038), and indistinguishable from antidepressant monotherapy. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> The findings indicate efficacy of lithium as a treatment for some aspects of major depressive disorder, especially as an add-on to antidepressants and for long-term prophylaxis. It remains uncertain whether some benefits of lithium treatment occur with many major depressive disorder patients, or if efficacy is particular to a subgroup with bipolar disorder-like characteristics or mixed-features. </jats:p></jats:sec>