Brain Circuits Determine Destiny in Depression: A Novel Approach to the Psychopharmacology of Wakefulness, Fatigue, and Executive Dysfunction in Major Depressive Disorder

Recent advances in neuropharmacology and neuroimaging are mapping the topography of symptomsin major depressive disorder (MDD). Different malfunctioning neuronal circuits apparently mediatedifferent symptoms in MDD. Since all patients with MDD do not have the same symptoms, thisimplies that they may not all have the same malfunctioning circuits. Furthermore, since MDD patientstreated with antidepressants commonly experience residual symptoms that prevent them from attainingcomplete remission, this implies that not all circuits are successfully targeted by treatment in suchpatients. A new neurobiologically informed treatment strategy for such patients calls for targeting residualsymptoms by augmenting antidepressants with agents capable of boosting specific neurotransmittersin the hypothetically malfunctioning circuits. With this approach, the frequently residualsymptoms of sleepiness, fatigue, and executive dysfunction can be targeted with bupropion, atomoxetine,modafinil, atypical antipsychotics, and stimulants.