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J Clin Pharm Ther. 2007 Oct;32(5):415-28.

Augmentation strategies for treatment-resistant depression: a literature review.

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Department of Medicine, Psychiatry Outpatient Clinics, Federal University of CearĂ¡, Fortaleza, CE, Brazil.



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.


Electronic databases and relevant textbooks were searched and the information retrieved was integrated in this review.


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.


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.

[Indexed for MEDLINE]

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