Up to 60% of depressed patients do not respond to two months of
pharmacotherapy, and late treatment responses are often correlated with poor outcomes and may be characterized as
treatment-resistant depression (TRD). Previous studies have noted that the addition of a psychostimulant such as
methylphenidate to the therapeutic regimen of patients with TRD or those depressed patients with comorbid
fatigue, advanced age, or a major medical illness showed significant improvement within two weeks. One explanation for the benefit of
methylphenidate in treating TRD is that it enhances the level of
dopamine in the brain. Adjunctive low dose
aripiprazole in patients with TRD has also become a common intervention. Several studies have focused on
aripiprazole's pharmacodynamic and pharmacokinetic profiles, but no definitive comments on its
antidepressant effects. We hypothesize that a low dose of
aripiprazole might play a role as a
dopamine agonist similar to that of
methylphenidate due to its partial
dopamine D2 agonist and 30% intrinsic dopaminergic activity. In addition to its use in patients with TRD, adjunctive
aripiprazole might work like
methylphenidate in those depressed patients with
fatigue, advanced age, or major illnesses. A new
drug invention which combined an
antidepressant with an adequate dose of
aripiprazole should be considered. The neurobiological basis for this combination in treating TRD awaits further study.