Is lithium augmentation effective in depression? J Aff Dis.Oct.2014


The 2007 Crossley & Bauer meta analysis clearly showed the benefit of lithium augmentation in depression. The effect size was large as well. (odds ratio  3.11  and NNT of 5). However,  lithium prescription do not reflect this possible benefit.Is it because the original evidence was more for lithium augmentation of TCAs and that we use less of them now a days?

Nelson et al report the results of meta analysis of all studies on this question. They included all double blind RCTS where Lithium or placebo was given after treatment failure with one antidepressant for 21 days ( at least). They identified 13 controlled studies of which 9 met all inclusion criteria. There were 237 patients in total.


OR for response was 2.89. heterogeneity was very  low ( all studies show effect in same direction). Lithium was effective whether it was combined with TCAs or newer antidepressants.NNT for response was 5. The confidence intervals for the OR is wide and hence the true NNT can be between 3 and 9.

Limitations:  Individual studies had small number of patients. ( 8 of 9 trials had fewer than 30 patients). One has to remember that met analytic results of smaller studies can sometimes be misleading.

Comments: Was bipolar status a factor in those who showed response?  There was not enough data to answer this question.

Tolerability of lithium is likely to be a factor in declining use. STARD found Lithium less tolerable than T3. Trials in this meta analysis did not show poor tolerability ( these were shorter trials and hence the tolerability issues may not have appeared).

Atypical antipsychotics as augmenting agents have taken over lithium in actual practice. The database is much larger for that as well.

Conclusion: Lithium is an effective augmenting agent when added to TCA or SSRI.

Summary of the article:

systematic review and meta-analysis of lithium augmentation of tricyclic and second generationantidepressants in major depression.

Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C. J Affect Disord. 2014 Oct 15;168C:269-275.

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