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 symptoms in major depressive disorder (MDD). Different malfunctioning neuronal circuits apparently mediate different symptoms in MDD. Since all patients with MDD do not have the same symptoms, this implies that they may not all have the same malfunctioning circuits. Furthermore, since MDD patients treated with antidepressants commonly experience residual symptoms that prevent them from attaining complete remission, this implies that not all circuits are successfully targeted by treatment in such patients. A new neurobiologically informed treatment strategy for such patients calls for targeting residual symptoms by augmenting antidepressants with agents capable of boosting specific neurotransmitters in the hypothetically malfunctioning circuits. With this approach, the frequently residual symptoms of sleepiness, fatigue, and executive dysfunction can be targeted with bupropion, atomoxetine, modafinil, atypical antipsychotics, and stimulants.