Lithium’s Emerging Role in the Treatment of Refractory Major Depressive Episodes: Augmentation of Antidepressants

Abstract

Background: The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants. Methods: To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes. Results: More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. Most of these studies were performed in unipolar depression and included all major classes of antidepressants, however mostly tricyclics. A meta-analysis including 10 randomized placebo-controlled trials has provided evidence that lithium augmentation has a statistically significant effect on the response rate compared to placebo with an odds ratio of 3.11, which corresponds to a number-needed-to-treat of 5. The meta-analysis revealed a mean response rate of 41.2% in the lithium group and 14.4% in the placebo group. One placebo-controlled trial in the continuation treatment phase showed that responders to acute-phase lithium augmentation should be maintained on the lithium-antidepressant combination for at least 12 months to prevent early relapses. Preliminary studies to assess genetic influences on response probability to lithium augmentation have suggested a predictive role of the –50T/C single nucleotide polymorphism of the GSK3β gene. Conclusion: Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants.

Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear

“…The plasma levels of lithium after 1 week of 0.2% Li 2 CO 3 treatments are within the recommended therapeutic range (0.5-1.2 mEq/l) (Suppes et al, 2008: Bauer et al, 2010.…”

“…Recently, many augmentation strategies have been developed to increase the effectiveness of antidepressant drugs. One such approach used in the treatment of psychiatric disorders is the addition of lithium to antidepressant drugs (Bauer et al, 2010;Chenu and Bourin, 2006).…”

Comparative efficacy and acceptability of seven augmentation agents for treatment-resistant depression: A multiple-treatments meta-analysis

“…[34] However, owing to a lack of RCTs that directly compared lithium to other augmentation agents RR = response rate; OR = odds ratio; CI = confidence interval; Li = lithium; TCAs = tricyclic antidepressants; AAPs = atypical antipsychotics; AEDs = antiepileptic drugs; T3 = tri-iodothyronine; CBT = cognitive behaviour therapy; BUS = buspirone. Li = lithium; TCAs = tricyclic antidepressants; AAPs = atypical antipsychotics; BUS = buspirone; AEDs = antiepileptic drugs; T3 = tri-iodothyronine; CBT = cognitive behaviour therapy.…”

Evidence for the Benefits of Nonantipsychotic Pharmacological Augmentation in the Treatment of Depression

“…However, few studies were conducted on SSRI nonresponders. Most of those studies were open label, and the results confirmed that augmentation with lithium was effective in TRD (Table 2) [20][21][22][23][24][25][26][27][28][29][30].…”