Augmentation Strategies in Resistant Depression - Some Are Effective and Well Tolerated

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Augmentation therapy for the management of depression involves the addition of a second drug to existing antidepressant therapy, with the aim of achieving an improved clinical response. This strategy is used when depression is treatment-resistant, or partially and/or insufficiently responsive to treatment, or to accelerate response to treatment. However, the use of augmentation therapy may also increase the risk of adverse effects.

While controlled clinical trials support the use of some combinations, a large proportion of data on the use of augmentation strategies is anecdotal and based on case reports. Lithium augmentation is one of the most widely used and best established options. Several placebo-controlled trials on the combined use of lithium with either tricyclic antidepressants (TCAs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) have provided positive evidence for the efficacy of lithium augmentation. Another popular choice for augmentation therapy, at least in some countries, is the addition of amfebutamone (bupropion) to SSRI therapy. Beneficial effects have been described in several reports but controlled trials appear to be lacking for this combination. Several other agents [e.g. thyroid hormones, valproic acid (sodium valproate), carbamazepine, psychostimulants, buspirone and pindolol] have been used as augmentation therapy with varying degrees of success. For example, pindolol in combination with SSRIs improves the speed of response compared with SSRI monotherapy.