Treatment-resistant depression in the age of serotonin: evolving strategies

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Abstract
Serotonin specific reuptake inhibitor antidepressants (SSRIs) have become the de facto first line treatment in pharmacotherapy of major depression. Albeit SSRIs have the advantage in tolerance and safety over older treatments, their ease of use does not circumvent the major enduring clinical problem of treatment resistant depression (TRD). For TRD in the setting of an SSRI failure recent data supports a range of strategies including switching, either to a second SSRI or out of the class to a non-SSRI antidepressant, or augmentation with the addition of lithium carbonate. Data concerning use of buspirone and pindolol, serotonin 1A receptor partial agonists, as augmentation agents in SSRI failure remains mixed. In contrast venlafaxine continues to look quite promising in TRD.