A Review of the Use of Augmentation Therapy for the Treatment of Resistant Depression: Implications for the Clinician

Abstract

Objective: To critically review the literature on augmentation therapy in resistant depression in order to assist the clinician to make a reasoned choice. Augmentation therapy is defined as the addition of a second agent to an existing antidepressant regimen with the aim of achieving improved clinical response.

Method: The available literature which related specifically to currently popular augmentation strategies in treatment resistant depression for the past 20 years was examined. The scientific evidence supporting the efficacy of these regimens and their safety was reviewed.

Results: Considerable research on lithium augmentation has been undertaken, and on triiodothyronine augmentation to a lesser degree. A number of other drugs have been trialled as augmentation agents with claims of success; however, most of the evidence supporting these agents is anecdotal and in the form of case reports. There are very few well-performed double-blind placebo-controlled studies of augmentation therapy.

Conclusions: Because of possible complex pharmacodynamic and pharmacokinetic interactions, augmentation therapy is not without its potential complications. Lithium augmentation of tricyclic antidepressants can be recommended as a safe and effective strategy and there is a body of scientific evidence supporting the addition of T₃ as an effective augmentation agent. Recent research with pindolol augmentation of selective serotonin re-uptake inhibitors (SSRIs) is encouraging, but these findings require replication. There is no empirical evidence supporting buspirone, carbamazepine, sodium valproate, methylphenidate or amphetamine as effective augmentation agents, or that adding a tricyclic to a SSRI has usefulness in relieving depressive symptoms. There is a need for considerable research in this area, with more prospective well-controlled placebo studies.