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Acceleration and Augmentation of Antidepressants
with Lithium for Depressive Disorders
Crossley N, Bauer M
Posted: September 2007  
Journal of Clinical Psychiatry 2007;68:935-940

Lithium has been suggested as a means to overcome delayed-onset and incomplete response to antidepressant therapy. Two recent meta-analyses support lithium augmentation of antidepressants but found little evidence that it accelerates response.

Augmentation:   A 1999 meta-analysis supported the efficacy of lithium augmentation, but a later study showed a negative effect, casting doubt on the evidence. The present analysis of placebo-controlled clinical trials comprised the 9 included in the original analysis and the trial with negative results, which may have failed to show an effect because of the noradrenergic profile of the antidepressant used (Nortriptyline). The total number of patients who received lithium was 131, and 138 received placebo. Most studies included a mix of diagnostic types, with unipolar depression predominating, and the antidepressant was most often a tricyclic.

The studies showed a greater than 3-fold odds of response to lithium vs. placebo with a number needed to treat of 5. Response occurred in significantly more lithium-treated patients (41% vs. 14%).

Acceleration:   For this analysis, the authors identified 5 studies in which lithium or placebo was started with an antidepressant in previously untreated patients. The studies included 113 patients taking lithium and 118 administered placebo. Numeric reductions in depression symptom scales were compared after the first and second week of treatment. Lithium was associated with a modest acceleration in symptom reduction that translated to a 3-point reduction in Montgomery-Asberg Depression Rating Scale score at 2 weeks and was not statistically significant. A secondary analysis of response rates after 1 and 2 weeks also showed a small, nonsignificant effect.