Can SSRIs Change Personality?

March 1, 2010

Section editor, Glen Spielmans, PhD

Ever since Peter Kramer wrote Listening to Prozac, we have suspected that SSRIs do more than simply treat depression; that they can make some patients “better than well.” That is, that they actually transform our patients’ underlying characters or personalities. But this is a tricky question to test, because it is devilishly hard to distin- guish improvement in personality from improvement in mood.

Recently, a group of researchers has made a valiant attempt to answer this question. In this study, 240 patients with major depressive disorder were random- ized to either paroxetine for 16 weeks (120 patients); cognitive therapy (CT) for 16 weeks (60 patients), or placebo for eight weeks (60 patients). The paroxetine dose ranged from 10 mg/day to 50 mg/day, and the CT was administered in twice-weekly 50-minute sessions for four weeks, followed by once or twice weekly 50-minute sessions for eight weeks, followed by once-weekly sessions forfour weeks.

The researchers measured improvement in depression with the standard Hamilton depression scale, and measured personality change with a well-validated scale called the NEO Five Factor Inventory. They choose two factors, neuroticism and extraversion, which are closely related to depression. “Neurot- icism” refers to a tendency to experience negative emotions, while “extraversion” refers to being social and experiencing positive emotions.

After eight weeks of treatment, patients assigned to both active treat- ments (paroxetine and CT) had greater improvement in depression scores than patients assigned to placebo. But in line with past studies, placebo was still a fair- ly effective antidepressant, producing 75% as much improvement in depression as the active treatments. The interesting finding was that while the active treat- ments robustly improved personality scores (“improved” here means a decrease in neuroticism scores and an increase in extraversion scores), placebo barely affected personality at all. In other words, both paroxetine and CT improved both personality and depression, where- as placebo improved depression without any personality change. The implication is that active antidepressant treatment— whether with medication or therapy— can tweak the underlying personality in some way.

The authors did other analyses to corroborate further the apparent inde- pendence of depression from personality scores. For example, for each placebo patient, they identified a matching paroxetine patient with the same amount of depression improvement. When they compared these two groups, the paroxe- tine group showed 3.5 times as much improvement on neuroticism as placebo, and 6.8 times as much improvement in extraversion (Tang TZ et al., Arch Gen Psychiatry 2009;66(12):1322–1330).

TCPR's Take: SSRIs and cognitive therapy appear to work in part by tweak- ing basic elements of the personality. One clinical implication is that during our sessions with depressed patients, we should probe for these specific personali- ty characteristics in an effort to decrease neuroticism and increase extroversion. This may work synergistically with other specific antidepressant techniques.

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