Depression and Prefrontal Cortex: All Roads Lead to Dopamine

A role for dopamine in the pathophysiology of depression was first proposed in 1975 and reviewed 20 years ago in this journal (1). The results of pharmacological treatment with dopaminergic drugs, however, have been inconclusive. Dopamine agonists such as pramipexole have shown modest clinical efficacy as antidepressants (2), and dopamine-releasing stimulants have either failed in randomized controlled trials or produced small and transient improvements in depressive symptoms (3). Furthermore, more efficacious antidepressants that modulate dopamine release or dopamine receptors also act on other monoamine receptors.