Antidepressant may change personality while relieving symptoms

Two personality traits, neuroticism and extraversion, have been related to depression risk, according to background information in the article. Individuals who are neurotic tend to experience negative emotions and emotional instability, whereas extraversion refers not only to socially outgoing behavior but also to dominance and a tendency to experience positive emotions. Both traits have been linked to the brain's serotonin system, which is also targeted by the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

Tony Z. Tang, Ph.D., of Northwestern University, Evanston, Ill., and colleagues studied the effects of one particular SSRI, paroxetine, in a placebo-controlled trial involving 240 adults with major depressive disorder. A total of 120 participants were randomly assigned to take paroxetine, 60 to undergo cognitive therapy and 60 to take placebo for 12 months. Their personalities and depressive symptoms were assessed before, during and after treatment.

All participants experienced improvement in their symptoms of depression. However, even after controlling for these improvements, individuals taking paroxetine experienced a significantly greater decrease in neuroticism and increase in extraversion than those receiving cognitive therapy or placebo. "Patients taking paroxetine reported 6.8 times as much change on neuroticism and 3.5 times as much change on extraversion as placebo patients matched for depression improvement," the authors write.

The findings provide evidence against a theory known as the state effect hypothesis, which proposes that any personality changes during SSRI treatment occur only as a result of alleviating depressive symptoms, the authors note. Several alternative explanations could be considered. "One possibility is that the biochemical properties of SSRIs directly produce real personality change," they write. "Furthermore, because neuroticism is an important risk factor that captures much of the genetic vulnerability for major depressive disorder, change in neuroticism (and in neurobiological factors underlying neuroticism) might have contributed to depression improvement."

SSRIs are widely used to treat depression, but understanding of their mechanisms are limited, the authors conclude; they have also been shown effective in treating anxiety disorders and eating disorders, conditions for which high neuroticism and low extraversion may also be a risk. "Investigating how SSRIs affect neuroticism and extraversion may thus lead toward a more parsimonious understanding of the mechanisms of SSRIs," they conclude.

The data set of this study came from a clinical trial supported by grants from the National Institute of Mental Health, Bethesda, Md. GlaxoSmithKline of Brentford, England, provided medications and placebo pills.