Box 2. Currently Available Antidepressant Treatments

The objective of this translational research Center is to utilize recent advances in chromatin biology, so-called epigenetics, to gain fundamentally increased understanding of the long-lasting abnormalities in the brain that cause depression and that mediate antidepressant responses. Our work focuses on key limbic brain regions, in particular, nucleus accumbens (NAc) and several areas of prefrontal cortex (PFC), which have been implicated directly in the control of mood in health and disease. Our goal and expectation is that this highly collaborative effort, among scientists at Mount Sinai School of Medicine in NYC, The Rockefeller University, UT Southwestern Medical Center at Dallas, Massachusetts Institute of Technology, and Massachusetts General Hospital, will provide an improved understanding of the molecular basis of these phenomena and lead to dramatically better treatments and diagnostic tests for depression and other stress-related illnesses.

Type of Treatment1 Mode of Action Examples
Tricyclics mixed NE, 5HT reuptake inhibitors imipramine, desipramine
SSRIs 5HT selective reuptake inhibitors fluoxetine, citalopram
NRIs NE selective reuptake inhibitors atomoxetine, reboxetine
SNRIs mixed NE, 5HT reuptake inhibitors venlafaxine, duloxetine
MAOIs monoamine oxidase inhibitors3 tranylcypromine, phenelzine
Lithium unknown4  
Atypicals unknown5 bupropion, mirtazapine, tianeptine
ECT general brain stimulation  
Magnetic stim.6 general brain stimulation7  
VNS6 unknown  
Psychotherapies learning8 cognitive-behavioral, interpersonal
1Many patients respond to several types of treatments, although it is not now possible to predict which patient will respond optimally to a particular treatment.
2Although they elevate mood in patients with depression, antidepressants do not elevate mood in normal individuals and are non-addictive.
3Inhibitors of MAOA, not MAOB, are effective antidepressants.
4Which of lithium's many molecular actions (e.g., inhibition of phosphatidylinositol phosphatases, adenylyl cyclases, glycogen synthase kinase 3β, G proteins and others) is responsible for its anti-manic and antidepressant actions is not known.
5Though atypical antidepressants have purported monoamine-based mechanisms (e.g., bupropion as a dopamine reuptake inhibitor, mirtazapine an α2-adrenergic antagonist, and tianeptine an activator of monoamine reuptake, these actions are not necessarily the mechanisms underlying the drugs' therapeutic benefit.
6Magnetic stimulation techniques and VNS remain experimental treatments, since their efficacy has not yet been established with certainty.
7The application of a magnetic field to the head is thought to affect the brain by inducing electric currents and neuronal depolarization, perhaps akin to what occurs during ECT.
8The active ingredient in psychotherapy is not known with certainty. However, it is thought to involve learning new ways to cope with problems.
9Electrical stimulation of a region of cingulate cortex, found to function abnormally in brain imaging scans, was reportedly antidepressant in a recent study of severely ill patients.
ECT, electroconvulsive therapy; VNS, vagal nerve stimulation.