Personality change during depression treatment: a placebo-controlled trial.

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

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 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 68 times as much change on neuroticism and 35 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, −12 SD, P P  = 08) or extraversion (008 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