Lithium augmentation in treatment-resistant-depression: Meta-analysis of placebo-controlled studies

The addition of lithium to the treatment regimens of previously nonrespondi ng depressed patients has been repeatedly investigated in controlled studie s. The authors undertook this meta-analysis to investigate the efficacy of lithium augmentation of conventional antidepressants. An attempt was made t o identify all placebo-controlled trials of lithium augmentation in refract ory depression. Only double-blind studies that involved participants who ha d been treated with Lithium or placebo addition after not responding to con ventional antidepressants were to be included in the meta-analysis. Further inclusion criteria mere the use of accepted diagnostic criteria for depres sion and the use of response criteria based on the acceptable measurement o f depression as an outcome variable. Studies were located by a search of th e MEDLINE database, a search in the Cochrane Library, and an intensive sear ch by hand of reviews on lithium augmentation. Nine of 11 placebo-controlle d, double-blind studies were included in this meta-analysis. Aggregating th ree studies with a total of 110 patients that used a minimum Lithium dose o f 800 mg/day, or a dose sufficient to reach Lithium serum levels of greater than or equal to 0.5 mEq/L, and a minimum treatment duration of 2 weeks, t he authors found that the pooled odds ratio of response during Lithium augm entation compared with the response during placebo treatment was 3.31 (95% confidence interval, 1.46-7.53). The corresponding relative response rate w as 2.14 (95% confidence interval, 1.23-3.70), the absolute improvement in r esponse rate was 27% (95% confidence interval, 9.8%-44.2%), and the number of patients needed tc, be treated to obtain one more responder was 3.7. Inc lusion of six more studies that fulfilled inclusion criteria but which trea ted subjects with additional lithium for less than 2 weeks or with a lower lithium dose (total, 234 patients) resulted in even higher estimates. Lithi um augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-b lind studies. The authors conclude from this meta-analysis that with respec t to efficacy, Lithium augmentation is the first-choice treatment procedure for depressed patients who fail to respond to antidepressant monotherapy.