Slowed Processing Speed Disrupts Patient Expectancy in Late Life Depression

Who benefits most from expectancy effects? A combined neuroimaging and antidepressant trial in depressed older adults

“…Study procedures are described in a previous report [ 12 ]. Briefly, 108 patients were enrolled in an 8-week antidepressant clinical trial experimentally manipulating expectancy (Fig.…”

“…Next, participants’ expectancy of improvement was experimentally manipulated by randomization to open administration of ADM (i.e., 100% probability of active medication, high expectancy condition) or placebo-controlled administration of ADM (i.e., perceived 50% probability of active medication, low-expectancy condition). This experimental procedure has been successful in manipulating the expectancy effect in multiple previous studies [ 4 , 12 ]. Participants receiving open medication began either escitalopram or duloxetine (depending on their past treatment history), while those in the placebo-controlled condition were randomized to medication or placebo in a 6:1 ratio favoring medication.…”

“…Expectancy effects may be weaker or more variable in older adults with MDD, as our past studies failed to successfully manipulate expectancy based on the probability of receiving active medication in an antidepressant trial [ 4 , 12 ]. Older adults with MDD are a population of great interest in identifying moderators of expectancy-based placebo effects because by virtue of brain aging they exhibit variability in cognitive (e.g., memory and executive function) and neural (e.g., integrity of frontostriatal tracts, white matter hyperintensities) markers that may be highly relevant to expectancy [ 13 , 14 ].…”

“…Consistent with this possibility, we recently found that decreased processing speed interfered with expectancy effects in older adults with MDD. There was a trend in the data suggesting that other neurocognitive features may be relevant moderators of expectancy, but the effect sizes for each were small and the individual moderation effects were non-significant [ 12 ].…”

“…Twelve potential moderators were chosen a priori based on the literature [ 24 ] focusing on cognitive and neuroimaging variables to create a combined moderator of expectancy effect. Specifically, we focused on cognitive performance deficits and white matter hyperintensities on T2-weighted magnetic resonance imaging because they are common in late-life depression, are associated with poor outcomes [ 13 , 14 , 25 ], and have been hypothesized to serve as the mechanisms underlying poorer expectancy effect [ 12 ]. We also included education [ 23 ] and age [ 4 , 22 ] because of previous research showing that these variables are associated with placebo effect.…”