New Approaches to the Treatment of Refractory Depression

Although the majority of patients with depression respond well to their initial pharmacologic treatment,as many as 30% to 45% fail to achieve an adequate response. In addition to the more traditionallithium and thyroid hormone augmentation strategies, a number of new pharmacotherapeutic approachesare currently being used to help manage refractory depression, including the addition of anotheragent or a switch to another antidepressant. Augmentation and switching strategies are often selectedin order to obtain a different neurochemical effect (e.g., adding a relatively noradrenergic agentto a relatively serotonergic antidepressant). In particular, several studies have suggested that depressedpatients refractory to treatment with selective serotonin reuptake inhibitors (SSRIs) may showa good response to newer agents that have a pharmacologic profile distinct from the SSRIs. Furthermore,preliminary studies have shown that the addition of SSRIs to either noradrenergic drugs such asthe tricyclic antidepressants (TCAs) or dopaminergic agents may be efficacious, even though concernsabout drug-drug interactions and tricyclic cardiac toxicity have limited the use of TCA-SSRIcombinations. The introduction of reboxetine, a relatively selective norepinephrine reuptake inhibitor,may increase the use of the latter therapeutic approach because of its improved safety profile comparedwith the TCAs. The review of treatment options for refractory depression that follows will outlinethe advantages, disadvantages, and level of support for a number of new treatment strategies.