A randomized trial of the effect of escitalopram versus placebo on cognitive function in healthy first-degree relatives of patients with depression

Abstract

The effect of selective serotonin receptor inhibitors (SSRIs) on healthy individuals remains unclear. The aim of the trial was to evaluate the effect of the SSRI escitalopram on cognitive function in healthy first-degree relatives of patients with major depressive disorder (FDRs). A total of 80 FDRs were randomized to escitalopram (10 mg/day) (n ¼ 41) versus placebo (n ¼ 39) for 4 weeks. Neuropsychological tests and ratings of mood were applied at entry (T0) and at 4 weeks (T4). The main outcome measure was calculated as the change (T4T0) in a general cognition score, which was the standardized mean of 13 test measures. Mean change in the general cognition score was not significantly increased with escitalopram compared with placebo (p ¼ 0.37) or for any of the specific tests. In univariate analyses no statistically significant correlations were found between change in the general cognitive score and the variables age, sex, Hamilton depression score 17 items, Danish Adult Reading Test-45, and plasma escitalopram levels, respectively. These results suggest that treatment with escitalopram does not improve or impair cognitive function in FDRs. Improvement in cognitive function following treatment of depressed patients with SSRIs seems to be related to the effects on depressive symptoms rather than to a direct effect of the SSRI.

Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

“…For study I, we recruited 24 rMD+ individuals (seven females), mean age ± s.d. = 28.6 ± 7.9 years, from a larger cohort ( n = 80) that had participated in the AGENDA trial (Associations Between Gene-Polymorphisms, Endo-Phenotypes for Depression and Antidepressive Intervention) (Knorr et al 2011 a , b , 2012 a , b ; Haastrup et al 2012) and 24 matched rMD− individuals (six females), mean age = 30.7 ± 9.4 years. Imaging data from one of the rMD− subjects were lost because of technical issues.…”

Effect of Chronic Escitalopram versus Placebo on Personality Traits in Healthy First-Degree Relatives of Patients with Depression: A Randomized Trial

“…The detailed trial protocol was published ahead of study completion and the changes in neuroticism scale scores on the NEO-PI-R and the EPQ were pre-defined outcomes [17]. Results on the primary outcome change in the area under the curve for cortisol measurements during the combined dexamethasone-corticotropin releasing hormone test have been reported elsewhere [18], thus neuroticism was a secondary outcome in addition to cognition published in [19].…”

Serotonin and brain function: a tale of two receptors

“…One possibility is that the observed pro-cognitive effects of SSRIs are actually mediated by other (non-1A) 5-HT receptors ( Boulougouris et al, 2008 ; Furr et al, 2012 ; Imoto et al, 2015 ), and another is that improvements in cognition in patients treated with SSRIs is an epiphenomenon of improvements in mood ( Chepenik et al, 2007 ). It is also important to note that the evidence that SSRIs improve cognition is relatively weak ( Beheydt et al, 2015 ; Knorr, 2012 ; Knorr et al, 2011 ; Siepmann et al, 2003 ) and their modest ability to address cognitive symptoms in depression is considered one of their limitations ( Popovic et al, 2015 ).…”