Augmentation strategies for treatment-resistant depression: a literature review

Abstract

Background: The large majority of depressed patients fail to remit on the first antidepressant prescribed. These patients with residual symptoms have higher relapse rates and poorer outcomes than those who remit. Treatment-resistant depression (TRD) is a therapeutic challenge for the clinician. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. The aim of this paper was to review the available evidence on the various augmenting agents that have been tested for efficacy in TRD. Methods: Electronic databases and relevant textbooks were searched and the information retrieved was integrated in this review. Results: Although augmentation strategies have been tested with various pharmacological agents, there are few controlled studies published. Lithium, triiodothyronine (T3), buspirone and pindolol have been most widely studied. Other agents include dopaminergic agents, atypical antipsychotics, psychostimulants, benzodiazepines ⁄ hypnotics, hormones and anticonvulsants. Conclusion: The augmentation therapy with the best evidence was the lithium-antidepressant combination, especially in patients not responding to tricyclic agents. However, good results have also been reported with augmentation strategies involving T3 and buspirone.

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

“…While its precise mechanism of action remains unclear, the rationale for studying its efficacy as an augmenting agent has been its potential to enhance 5-HT tone in a way that might augment the clinical effects of SSRIs and SNRIs [2]. While several open-label trials have suggested a benefit of buspirone augmentation [9], 2 RCTs failed to find a significant advantage [95,96].…”

“…The Global Burden of Disease Study 2010 indicates that major depression is a leading cause of disability-adjusted life years worldwide [1]. Despite the widespread availability of effective treatments for depression, many patients do not achieve adequate symptomatic relief [2]. …”

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

“…For example, under naturalistic clinical conditions, only about 35% of depressed patients achieve full clinical remission within 8−12 weeks of treatment with citalopram, a selective serotonin reuptake inhibitor (Trivedi et al 2006). Even after sequential treatments with alternatives, including augmentation strategies, a considerable percentage of the patients fail to remit (Fava and Davidson 1996;Carvalho et al 2007). Apparently, the various antidepressants induce cellular mechanisms beyond monoamine receptors, and successive time-consuming changes in neuronal and glial circuitries determine the clinical effects of an antidepressant medication (Nestler et al 2002).…”

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial

“…120 Although many different strategies have been evaluated, to date there is little robust evidence regarding the effectiveness of many of these strategies, 13 with reviews frequently incorporating evidence from uncontrolled studies and/or non-randomised studies as well as RCTs. [121][122][123] Furthermore, there is little evidence for the effectiveness of other psychological therapies as an adjunct to pharmacotherapy. Although CBT is, at present, the psychological treatment that is most frequently available on the NHS, it is evident that from CoBalT that other psychological treatment approaches may be preferred by some patients.…”