Taking an antidepressant can lead to significant personality changes, likely for the better, a new study finds.

The study looked at the effects of taking selective serotonin reuptake inhibitors (SSRIs), which are widely used to treat depression today, and found that those who took these antidepressants experienced more positive emotions, were more outgoing and more emotionally stable in the long-term.

"Our findings lead us to propose a new model of antidepressant mechanism," said Tony Z. Tang of Northwestern University in Chicago. "Our data suggests that modern antidepressants work partly by correcting key personality risk factors of depression."

Neuroticism and extroversion

Tang and colleagues studied the effects of the SSRI paroxetine (Paxil and Seroxat) as compared to a placebo in a trial involving 240 adults with major depressive disorder.

Those taking the paroxetine showed substantial improvements in their depression compared to those taking a placebo, as has been shown in many other studies. But the SSRI-takers also saw a significant decrease in neuroticism and an increase in extroversion compared to those taking the placebo.

Neuroticism and extraoversion are two fundamental parts of human personalities. Neuroticism refers to a tendency to experience negative emotions and emotional instability, whereas extroversion refers not only to socially outgoing behavior but also to dominance and a tendency to experience positive emotions.

Recent research has found that neuroticism is a key risk factor of depression, and that there is substantial overlap in the genes associated with high neuroticism and the genes associated with depression.

Both neuroticism and extraversion are associated with the brain's serotonin system, which is targeted by SSRI antidepressants.

Sixty-nine of the original 120 people who took paroxetine followed up with researchers for one year. The changes in levels of neuroticism and extroversion before and after treatment for those antidepressant users were compared to placebo patients who showed the same amount of improvement in their depression symptoms. The study found that there was 6.8 times as much change on neuroticism and 3.5 times as much change on extroversion in those who took paroxetine as in placebo patients.

Personality changes

The findings provide evidence against the common assumption that personality changes during SSRI treatment occur only as a byproduct of alleviating depressive symptoms, the researchers note. Several alternative explanations could be considered.

"One possibility is that the biochemical properties of SSRIs directly produce real personality change," the researchers wrote in the December issue of the journal Archives of General Psychiatry. And because neuroticism is an important risk factor for depression, it may have been improvements in neuroticism that contributed to the improvements in depression, they added.

In this study, the advantage of paroxetine over placebo in changing personality appears far more drastic than its advantage over placebo in alleviating depression, the researchers note. SSRIs also could effectively treat many anxiety disorders and eating disorders, conditions for which high neuroticism and low extroversion may also be key risk factors.

SSRIs perhaps can be viewed as personality-normalizing agents, useful in treating many disorders associated with high neuroticism and low extroversion, the researchers conclude, though Tang notes that the findings must be reproduced in other studies before any firm conclusions can be drawn.

The work was supported by the National Institute of Mental Health; GlaxoSmithKline provided medications and placebo pills.