Slowed Processing Speed Disrupts Patient Expectancy in Late Life Depression

ABSTRACT Objective Slowed processing speed and executive dysfunction are associated with poor outcomes in Late Life Depression (LLD), though it is unclear why. We investigated whether these variables interfere with the development of positive treatment expectancies in an antidepressant trial. Methods Depressed older subjects were randomized to Open (intended to increase patient expectancy) or Placebo-controlled (termed ‘Hidden,’ intended to decrease expectancy) administration of antidepressant medication for 8 weeks. Analysis of covariance analyzed the between-group difference on expectancy (Credibility and Expectancy Scale [CES]) and depression (Hamilton Rating Scale for Depression [HRSD], Clinical Global Impressions [CGI] Severity). Moderator analyses examined whether these Open vs. Hidden differences varied based on higher vs. lower processing speed and executive function. Results Among the 108 participants, a significant between-group difference was observed on expectancy (effect size [ES, Cohen's d]=0.51 on CES Item 2; ES=0.64 on Item 4), indicating the manipulation was effective. Processing speed as measured by the Stroop Color-Word Test (number color-words named in congruent condition) was a significant moderator of the Open vs. Hidden effect on expectancy. Depressive symptom improvement was greater on average for Open vs. Hidden participants who received active drug (CGI-severity ES=1.25, HRSD ES=0.41), but no neurocognitive moderators of the between-group difference reached statistical significance. Conclusions Slowed processing speed impairs the development of expectancies in antidepressant trials for LLD, which may help explain lower antidepressant response among older adults. Future studies may address whether interventions to optimize treatment expectancies are capable of improving treatment outcomes.