Aripiprazole: a dopamine modulator that mimics methylphenidate in producing faster antidepressant effects

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.