Clarification added January 6, 2010.

A wealth of research has shown that selective serotonin reuptake inhibitors (SSRI) are effective at reducing the symptoms of depression—though new research suggests that study populations limited to those with severe depression may skew these findings, and that antidepressants only show truly significant benefits over placebo in patients with major depressive disorder.* A new study out of Northwestern University may shed some new light on how these antidepressants impact personality—and whether that influence may in fact be key to their success in combating depression. In a placebo-controlled study of 240 adults with major depressive disorder, psychologist Tony Tang and colleagues found that, not only did participants taking the medication show improved reduction in depression symptoms compared with those taking the placebo, but that they also showed marked differences in personality—exhibiting less neuroticism and more extroversion, in particular. 

The findings, published in the December issue of the Archives of General Psychiatry, suggest that the mechanism through which antidepressants function may be by altering personality traits that often characterize depression. Previous study has shown that high levels of neuroticism can indicate a risk for depression, while other research has found a substantial overlap in the genes associated with both depression and severe neuroticism. Additionally, earlier investigations have shown that both neuroticism and extroversion are associated with the brain's serotonin processing systems, which are targeted by SSRI antidepressants.

In this most recent study, 120 participants were randomly assigned to take the antidepressant paroxetine (Paxil and Seroxat), and, as in most trials of antidepressants, researchers found that they exhibited slightly greater improvement in depression symptoms compared with participants taking the placebo. Yet, when researchers analyzed how the SSRI impacted personality, they found that people in the trial group showed a dramatic decrease in neuroticism and increase in extroversion not seen in the control group. Compared with the placebo group, on average, participants who took paroxetine had a 6.8-fold change in signs of neuroticism, and 3.5 times as much change in signs of extroversion.

The study authors are hopeful that this latest research might pave the way for continued research into the mechanism through which SSRIs help patients battle depression. 

*This was added in light of a study released on January 5, 2010 by the Journal of the American Medical Association finding little benefit of antidepressants to patients with mild and moderate depression.