Antidepressant medications taken by roughly 7% of American adults cause profound personality changes in many patients with depression, far beyond simply lifting the veil of sadness, a study has found.

Researchers saw strong drops in neuroticism and increases in extroversion in patients taking antidepressants, two of five traits thought to define personality and shape a person’s day-to-day thoughts and behavior. The findings are striking, researchers said, because psychologists have long thought that such fundamental traits are moorings of an adult’s personality that shift very little over a lifetime.

The medications would seem to relieve depression by chemically altering brain processes that spawn negative thoughts rather than just alleviating symptoms associated with a depressed state, said Northwestern University psychologist Tony Z. Tang, the lead author of the study.

The findings, published in the journal Archives of General Psychiatry and funded by the National Institute of Mental Health, could have significant implications for depression treatment, researchers not connected with the study said.


It is unclear how long-lasting the changes in personality are, the authors said. But the study found that patients whose personalities shifted the most were less likely to relapse. And they said that monitoring those altered traits could be a useful, early gauge of whether a medication is working and how probable a recurrence would be.

The findings are likely to rekindle debate on the impact and effectiveness of selective serotonin reuptake inhibitors, or SSRIs, on which Americans spent $9.6 billion last year alone. SSRIs increase the availability of serotonin, a key brain chemical, low levels of which are linked to depression.

The trial involved 240 adults with moderate to severe depression. Of those, 120 were given the selective serotonin reuptake inhibitor paroxetine (Paxil) for 16 weeks. Another 60 received cognitive therapy but no medication for 16 weeks, and 60 others were given a placebo alone for eight weeks.

All subjects who reported improvements in their depression in response to psychotherapy or medication were followed for a year.


Patients who received paroxetine were more likely to have their symptoms ease than patients in the other two groups, and they showed more dramatic personality changes.

Those given placebo pills reported early improvements in their depressive symptoms almost as great as those reported by those on medication, but their underlying personalities “didn’t budge,” said Northwestern’s Tang. And their relief from depressive symptoms was briefer and more muted than the improvement of those on medication or cognitive therapy. They were given the antidepressant if their condition failed to improve after eight weeks.

That finding “pokes a hole” in the charges of many critics that SSRIs are little more effective at treating depression than sugar pills, said UCLA psychiatrist Andrew Leuchter.

Still, several researchers not involved in the study cautioned that the findings might prompt greater use of medications for which U.S. physicians already write 164.2 million prescriptions a year. For insurers and healthcare policymakers wary of the high cost of psychotherapy, the study might make the drugs look like a better value.


That would be a mistake, said University of Illinois psychologist Brent Roberts. Not all depressed patients respond to SSRIs so favorably. “And it would be foolish to base policy on the findings of one study,” he said.

Other studies will be necessary before the cost-effectiveness of different treatments can be established, Roberts added.

The personality changes in the study were striking, researchers said. While adults typically become slightly less neurotic with age, it is a gradual change. In the study, experimental subjects who responded to SSRI treatment changed roughly twice as much on the neuroticism scale as most adults do in a lifetime. And they did so in eight weeks.

“That is a dramatic change,” said Robert McCrae, a leading researcher on personality, now retired. “If you were these patients or someone in their family, you’d notice a difference.”


The study also suggests a new measure to identify people at risk of developing depression and to predict who would benefit most from a particular medication or therapy. Doctors could refer to a personality inventory that would measure a patient’s “big five” traits -- neuroticism and extroversion, as well as agreeableness, conscientiousness and openness -- to test a patient’s early response to a drug or psychotherapy.

Such a tool could improve the trial-and-error method of prescribing that is common in the treatment of depression, UCLA’s Leuchter said.

To drive down the rate of relapse in depression, Tang said, psychiatrists should focus on helping patients achieve fundamental personality changes and not just recover from a current episode of depression. Roughly half of those treated successfully for the disorder can be expected to suffer a recurrence in the following year.

“They should be thinking how to prevent relapse -- not just about short-term recovery, which we’re pretty good at -- as soon as the patient walks through their door,” Tang said.


melissa.healy@latimes.com