Medications frequently prescribed for depression may not lighten a person’s mood until they brighten his or her personality. A new study suggests that the antidepressant medication paroxetine, or Paxil, fights depression most effectively when it first modifies two personality traits that predispose people to this mood disorder.

The two traits, high neuroticism and low extraversion, have already been linked to depression. Depressed patients taking Paxil reported much greater change in these traits, as assessed via scores on personality tests, than patients given placebo pills. The difference was notable even after accounting for the extent to which each treatment diminished standard measures of depression, says psychologist Tony Tang of Northwestern University in Evanston, Ill. Patients who experienced especially pronounced personality change during four months of Paxil treatment displayed a particularly low depression relapse rate over the next year of treatment, Tang’s team reports in the December Archives of General Psychiatry.

“We propose that modern antidepressants work partly by correcting the long-term personality risk factors for depression,” Tang says.

Like many other researchers and clinicians, Tang’s group initially suspected that personality changes observed during treatment with SSRIs (short for selective serotonin reuptake inhibitors) such as Paxil occur as a result of alleviating depression. But the new findings suggest that Paxil exerts an independent effect on personality that contributes to the lessening of depression.

“This is more evidence than I’ve seen before that personality changes drive antidepressant responses, but it’s still a small study,” remarks psychiatrist Andrew Leuchter of the University of California, Los Angeles.

As measured on a standard personality questionnaire, high neuroticism involves a tendency to experience negative emotions and emotional instability. Low extraversion refers to a lack of sociability, assertiveness and upbeat feelings. Both of these personality traits have been linked to the action of a chemical messenger in the brain called serotonin. Paxil and other medications in the SSRI class of antidepressants increase levels of serotonin available to brain cells.

For reasons that remain unclear, only about 1 in 3 depressed patients will experience remission when taking one of the SSRIs. When SSRIs work, patients become more outgoing and develop closer relationships with others, Leuchter notes.

Tang’s team studied 240 outpatients, ages 18 to 70, with moderate to severe depression. The researchers randomly assigned 120 volunteers to receive Paxil, 60 to undergo weekly cognitive therapy sessions and 60 to take placebos. After four months of treatment, 34 patients who responded well to individually adjusted doses of Paxil and 35 who did well on cognitive therapy received follow-up treatment for the next year.

After taking placebos for two months, 31 patients opted for Paxil treatment.

As in earlier studies (SN: 3/1/08, p. 132), placebo patients reported much the same depression improvement as did patients receiving either Paxil or cognitive therapy. But on measures of personality traits, Paxil patients reported substantially lower neuroticism and higher extraversion after two months, compared with moderate personality changes for cognitive therapy patients and minimal changes for placebo patients.

Among the 69 patients who improved on Paxil, only eight of 23 who displayed large drops in neuroticism scores relapsed over the follow-up period, compared with majorities of those who showed moderate or small neuroticism declines.

Drops in neuroticism scores in patients undergoing cognitive therapy did not predict lower relapse rates. Personality changes during cognitive therapy may arise as a by-product of diminishing depression, Tang suspects.

If the new findings are confirmed in larger samples and with other SSRIs, it will raise the controversial possibility of using antidepressants to alter the personalities of non-depressed individuals with high neuroticism and low extraversion, Tang says. Studies of SSRI treatment applied to such individuals have not been conducted.

For more information about research conducted by Tony Tang and his colleagues http://tinyurl.com/yknokgq

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