Background
High neuroticism is a personality risk factor that captures 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 MDD patients in selective serotonin reuptake inhibitors (SSRIs) treatment 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/Setting
Personality was measured during a placebo-controlled trial in research clinics.
Patients
Adult moderate-to-severe MDD patients randomized to receive paroxetine (n=120), placebo (n=60), or cognitive therapy (CT) (n=60).
Outcome Measures
NEO Five-Factor Inventory; Hamilton Rating Scale for Depression.
Results
Paroxetine patients reported greater personality change than did placebo patients, even after controlling for depression improvement (p≤.002). The advantage of paroxetine over placebo in antidepressant efficacy was no longer significant after controlling for change in personality (p≥.14). Paroxetine patients 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 (−1.2 SD, p<.001), they reported little change on neuroticism (−0.18 SD, p=.08) or extraversion (0.08 SD, p=.50). CT 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 CT responders (p=.86).
Conclusion
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.