Major depression and metabolic encephalopathy: Syndromes more alike than not?

Abstract

The seminal discovery of the antidepressant imipramine in 1958, the mood-stabilizing actions of lithium ion in 1949, and that these drugs work by increasing or modulating synaptic levels of one or more monoamine such as serotonin (5HT), noradrenaline (NA) or dopamine (DA), have set the gold standard for drug research and treatment in mania and depression. However, drug discovery has not realized its full potential and in many ways is decades behind our understanding of psychiatric illness. Our newest drugs for these disorders, such as the 5HT reuptake inhibitors (SRI, e.g., fluoxetine (Prozac®)), are not any more effective than imipramine in the treatment of depression (Geddes et al., 2000) while after more than 50 years, lithium salts still remain the bench mark treatment for manic depression (Compton and Nemeroff, 2000).