Personality change during depression treatment: a placebo-controlled trial

Abstract

Context: High neuroticism is a personality risk factor that reflects much of the genetic vulnerability to major depressive disorder (MDD), and low extraversion may increase risk as well. Both have been linked to the serotonin system.

Objectives: To test whether patients with MDD taking selective serotonin reuptake inhibitors (SSRIs) report greater changes in neuroticism and extraversion than patients receiving inert placebo, and to examine the state effect hypothesis that self-reported personality change during SSRI treatment is merely a change of depression-related measurement bias.

Design: A placebo-controlled trial.

Setting: Research clinics. Patients Adult patients with moderate to severe MDD randomized to receive paroxetine (n = 120), placebo (n = 60), or cognitive therapy (n = 60).

Outcome measures: NEO Five-Factor Inventory and Hamilton Rating Scale for Depression.

Results: Patients who took paroxetine reported greater personality change than placebo patients, even after controlling for depression improvement (neuroticism, P < .001; extraversion, P = .002). The advantage of paroxetine over placebo in antidepressant efficacy was no longer significant after controlling for change in neuroticism (P = .46) or extraversion (P = .14). 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. Although placebo patients exhibited substantial depression improvement (Hamilton Rating Scale for Depression score, -1.2 SD, P < .001), they reported little change on neuroticism (-0.18 SD, P = .08) or extraversion (0.08 SD, P = .50). Cognitive therapy produced greater personality change than placebo (P </= .01); but its advantage on neuroticism was no longer significant after controlling for depression (P = .14). Neuroticism reduction during treatment predicted lower relapse rates among paroxetine responders (P = .003) but not among cognitive therapy responders (P = .86).

Conclusions: Paroxetine appears to have a specific pharmacological effect on personality that is distinct from its effect on depression. If replicated, this pattern would disconfirm the state effect hypothesis and instead support the notion that SSRIs' effects on personality go beyond and perhaps contribute to their antidepressant effects.

Figure 1

A flow chart of the clinical trial patients utilized in our analyses.

Figure 2. Time courses of depression, neuroticism, and extraversion for the placebo patients who opted for subsequent SSRI treatment after week 8

The figure is based on the 31 placebo patients who took inert-placebo from intake to week 8 and then opted for SSRI treatment from week 8 to week 16. Error bars reflect standard errors.

Figure 3. The state-effect hypothesis and two alternative hypotheses

Depression etiology research has not determined whether neuroticism and extraversion are causes of depression or risk factors reflecting other underlying causes of depression. The cause-correction hypothesis retains this ambiguity in that changes in neuroticism/extraversion and changes in factors underlying neuroticism/extraversion might both contribute to depression improvement.