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

Background. Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Augmentation pharmacotherapy is effective for TRD, but it is still unclear which augmentation agent is most efficacious.

Objective. To assess the effects of seven augmentation agents on TRD.

Methods. We did a multiple-treatments meta-analysis, accounting for both direct and indirect comparisons. PubMed, the Center for Clinical and Translational Research, Web of Science, Embase, CBM-disc, the Chinese National Knowledge Infrastructure and relevant websites (up to August 2013) were searched for randomised controlled trials (RCTs) about augmentation agents. The following terms were used: ‘potentiation’, ‘augmentation’, and ‘adjunct’ paired with ‘depression’ and ‘resistant depression’. No language limitation was imposed.

Results. We systematically reviewed 12 RCTs (1 936 participants), which included seven augmentation agents: lithium, tricyclic antidepressant (TCA), atypical antipsychotics (AAPs), antiepileptic drugs (AEDs), buspirone, cognitive behaviour therapy (CBT) and tri-iodothyronine (T3). The results revealed that T3 was more efficacious than lithium, TCA, AAPs, AEDs, buspirone and CBT with odds ratios (ORs) of 1.58, 1.56, 1.51, 1.47, 1.77 and 1.25, respectively. ORs favoured CBT compared with lithium, TCA, AAPs, AEDs and buspirone. Buspirone was the least efficacious of all the other augmentation agents tested. AAPs were significantly more acceptable than lithium, and CBT more than buspirone. T3 was slightly more acceptable than lithium, and CBT more than AAPs.

Conclusion. T3 as an augmentation agent should be a clinician’s first consideration instead of lithium in acute treatment for TRD. CBT might be a good augmentation agent in some communities. Buspirone should be a final option as an augmentation agent. Further research is needed, such as a well-designed, large-scale controlled trial, to support and draw definite conclusions.