The International Journal of Neuropsychopharmacology

Research Article

Use of adjunctive stimulants in adult bipolar depression

Bernardo Dell'Ossoa1 c1 and Terence A. Kettera2

a1 Department of Psychiatry, University of Milan, Fondazione IRCCS Ca'Granda, Ospedale Maggiore Policlinico, Milan, Italy

a2 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA


Bipolar depression represents a high priority research field, due to its pervasiveness, and high economic and personal (suicidality, impaired function, quality of life) costs, and the limited evidence base to inform therapeutics. Mood stabilizers and second-generation antipsychotics for bipolar depression are commonly only partially effective, and their side-effects may overlap with depressive symptoms such as hypersomnia, daytime drowsiness, fatigue, psychomotor retardation, and weight gain. Moreover, the use of antidepressants in bipolar depression is controversial due to concerns regarding the risks of inefficacy or switching to mood elevation. Stimulants and related compounds such as modafinil and armodafinil have on occasion been used as adjuncts in bipolar depressed patients with encouraging results, but their use is limited by the paucity of systematic evidence of efficacy and safety. The present review aims to provide an updated perspective on the use of stimulants and stimulant-like medications in adult bipolar depression, considering not only recent randomized controlled trials, but also open naturalistic studies, in order to clarify the strengths and limitations of using these agents.

(Received September 05 2011)

(Reviewed February 08 2012)

(Revised March 01 2012)

(Accepted March 13 2012)

(Online publication April 13 2012)

Key words

  • Armodafinil;
  • bipolar depression;
  • methylphenidate;
  • modafinil;
  • stimulants