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

Abstract

IntroductionThe serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD).MethodsThe trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention.ResultsWhen compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (−1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6).ConclusionIn healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness.Trial RegistrationClinicaltrials.gov NCT00386841

A randomized placebo‐controlled trial examining the effects of escitalopram on neuroticism and state anxiety in a nonclinical sample

“…Although nonsignificant, disparate results between factors suggest that it could be useful for future research to at least consider the possibility of finding different effects on neuroticism facets/factors in addition to total scores. There was also a small, borderline statistically significant difference between escitalopram and placebo on HAM‐A scores that was more comparable in size to the effect of escitalopram on NEO‐PI‐R neuroticism ( d = .39, p = .09) reported previously (Knorr et al, ). The larger effect on HAM‐A scores is not surprising, as this scale focuses on somatic anxiety (e.g., palpitations and muscle tension) and was designed to be sensitive to change during psychiatric treatment (Hamilton, ).…”

“…This study expanded upon the original trial analysis by separating EPQ neuroticism into trait anxiety and mood instability factors (Knorr et al, ; Knorr et al, ). It is interesting that there was a small difference favoring escitalopram over placebo on EPQ trait anxiety that was not apparent for EPQ mood instability or total EPQ neuroticism, although it was not statistically significant and should be interpreted as a null result.…”

“…The effect of selective serotonin reuptake inhibitors (SSRIs) on the personality domain of neuroticism in placebo-controlled trials has been inconsistent (Knorr et al, 2012;Simmons & Allen, 2011;Tang et al, 2009). Positive results were found in two studies that measured neuroticism with the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R; Tang et al, 2009) and the Zuckerman-Kuhlman Personality Questionnaire (Simmons & Allen, 2011).…”

Possible role of more positive social behaviour in the clinical effect of antidepressant drugs

“…Personality inventories are not designed to detect changes occurring over weeks, and laboratory tests are not necessarily indicative of behaviour in everyday life. Nonetheless, several studies, including the 2 largest -those of Kamarck and colleagues 24 and Knorr and colleagues 26 -found changes consistent with improvements in behaviour along the agreeable-quarrelsome dimension. Thus, the studies provide modest support for the idea that antidepressants may decrease ag on istic and increase affiliative social behaviours in humans.…”

“…Among the changes induced by sertraline were decreases in guilt and attentiveness and increases in joviality and self-assurance, but there was no change in hostility. Finally, Knorr and colleagues 26 examined the effect of 4 weeks of treatment with the SSRI escitalopram or placebo on personality inventory scores in 80 first-degree relatives of patients with a history of major depressive disorder. Escitalopram did not alter neuroticism, extraversion, psychoticism, openness or conscientiousness, but increased agreeableness.…”