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Pharmacological treatment approaches to difficult-to-treat depression

This is a republished version of an article previously published in MJA Open

It is widely accepted that at least one in three patients with depression will not respond adequately to a series of appropriate treatments.1 There have been several approaches to defining this difficult-to-treat depression. One recently developed proposal is the Maudsley staging method — a points-based model of degrees of treatment resistance, which takes into account details of the specific treatments employed and the severity and duration of the depression.2 Another widely used and more straightforward definition is the failure to respond to two adequate trials of antidepressants from different pharmacological classes.3

Here, we use a pragmatic definition of difficult-to-treat depression — failure to respond to an adequate course of a selective serotonin reuptake inhibitor (SSRI) antidepressant. This was the definition used in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial in the United States,4

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