July 9, 2021

When we think about patient characteristics that influence health, disease, and clinical research, we tend to think about things like vital statistics, medical history and genetic makeup – while patient personality or psychology is often overlooked. In reality, the importance of personality has been under scrutiny for centuries and dates back to Greek and Roman times1. More recently, the emergence of psychoanalysis in the 1950’s led to hypotheses on the connection between the body and the mind. Truly, however, the emergence of the Big Five approach ((extraversion, agreeableness, conscientiousness, emotional stability, and intellect/openness) to quantify personality2 has enabled better understanding of the relationship between personality traits and health. 

Several seminal studies have related the Big Five to self-reported mental and physical health.  In one study, Big Five traits of conscientiousness and emotional stability were consistently and strongly related to better health3. In other research, longitudinal studies have been conducted to evaluate the relationship between mortality risk and personality traits. Some works have reported that people with higher neuroticism are at higher risk of dying4,5, while the reverse is true for openness6–8

Another area of interest has been the relationship between response to treatment and personality. For example, in a recent publication, Angela Fang and co-authors showed that patients suffering from body dysmorphic disorder displayed higher levels of neuroticism and lower levels of extraversion than a normed reference group and that higher baseline neuroticism was a significant predictor of nonresponse to escitalopram treatment9. Other studies have shown relationships between personality traits and response to treatments for depression10, substance abuse11, heart disease12 and even tinnitus13

In reality, this body of research is so broad that it would be impossible to cover it in a simple blog. It does, however, demonstrate that we cannot underestimate the link between who we are and how we react to heatlh disorders, diagnosis, and even treatment.

While these observations were made in “real world” scenarios, similar impacts might be observed when conducting clinical trials evaluating the efficacy of new treatments. The gold standard of drug development involves evaluating treatment efficacy in patients receiving active drug vs. those receiving placebo – and both treatment response and placebo response are inevitably influenced by patient personality. Indeed, extensive research has been conducted on the relationship between placebo response and patient psychological traits. The placebo response clearly varies between patients and is heavily influenced by the patient’s expectations (in terms of drug efficacy and overall well-being) and certain well-defined personality traits14–18.  Consequently, the patient-specific nature of the placebo effect may introduce bias and/or variability in randomized clinical trials.

While the relationship between the placebo response and patient personality has been well-documented in academic settings, capitalizing on this understanding in a way that is applicable and scalable for industry-sponsored clinical trials has proven to be much more difficult. After nearly a decade of research, the Placebell©™ method combined a sophisticated evaluation of key components of patient psychology critical to the placebo response with machine learning to reduce the impact of the placebo response in clinical trials. Now, using Placebell©™, drug developers can quantify patient personality and reduce its contribution to data variability using the covariate approach, thus improving the ability to distinguish treatment efficacy.

For more information about how Placebell©™ can improve clinical trial success rates by considering the impact of individual patient psychology, please contact us.


1.        Hampson SE. Personality and Health. Oxford Research Encyclopedia of Psychology. Published online December 19, 2017. doi:10.1093/ACREFORE/9780190236557.013.121

2.        Costa PT, Mccrae RR. The Five-Factor Model, Five-Factor Theory, and Interpersonal Psychology. Handbook of Interpersonal Psychology: Theory, Research, Assessment, and Therapeutic Interventions. Published online March 16, 2012:91-104. doi:10.1002/9781118001868.CH6

3.        Goodwin RD, Friedman HS. Health Status and the Five-factor Personality Traits in a Nationally                Representative Sample: 2016;11(5):643-654. doi:10.1177/1359105306066610

4.        Wilson RS, Mendes de Leon CF, Bienias JL, Evans DA, Bennett DA. Personality and Mortality in Old Age. The Journals of Gerontology: Series B. 2004;59(3):P110-P116. doi:10.1093/GERONB/59.3.P110

5.        Grossardt BR, Bower JH, Geda YE, Colligan RC, Rocca WA. Pessimistic, Anxious, and Depressive Personality Traits Predict All-Cause Mortality: The Mayo Clinic Cohort Study of Personality and Aging. Psychosomatic Medicine. 2009;71(5):491-500. doi:10.1097/PSY.0B013E31819E67DB

6.        E F, PA B. Openness to experience and all-cause mortality: a meta-analysis and r(equivalent) from risk ratios and odds ratios. British journal of health psychology. 2012;17(1):85-102. doi:10.1111/J.2044-8287.2011.02055.X

7.        Roberts BW, Kuncel NR, Shiner R, Caspi A, Goldberg LR. The Power of Personality: The Comparative Validity of Personality Traits, Socioeconomic Status, and Cognitive Ability for Predicting Important Life Outcomes: 2016;2(4):313-345. doi:10.1111/J.1745-6916.2007.00047.X

8.        Turiano NA, Chapman BP, Gruenewald TL, Mroczek DK. Personality and the leading behavioral contributors of mortality. Health Psychology. 2015;34(1):51-60. doi:10.1037/HEA0000038

9.        Fang A, Porth R, Phillips KA, Wilhelm S. Personality as a Predictor of Treatment Response to Escitalopram in Adults with Body Dysmorphic Disorder. Journal of psychiatric practice. 2019;25(5):347. doi:10.1097/PRA.0000000000000415

10.      Kim SY, Stewart R, Bae KY, et al. Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: A randomised controlled trial. Journal of Affective Disorders. 2016;203:38-45. doi:10.1016/J.JAD.2016.05.071

11.      Müller SE, Weijers H-G, Böning J, Wiesbeck GA. Personality Traits Predict Treatment Outcome in Alcohol-Dependent Patients. Neuropsychobiology. 2008;57(4):159-164. doi:10.1159/000147469

12.      Denollet J, Vaes J, Brutsaert DL. Inadequate Response to Treatment in Coronary Heart Disease. Circulation. 2000;102(6):630-635. doi:10.1161/01.CIR.102.6.630

13.      Simões J, Schlee W, Schecklmann M, Langguth B, Farahmand D, Neff P. Big Five Personality Traits are Associated with Tinnitus Improvement Over Time. Scientific Reports 2019 9:1. 2019;9(1):1-9. doi:10.1038/s41598-019-53845-4

14.      Kern A, Kramm C, Witt CM, Barth J. The influence of personality traits on the placebo/nocebo response: A systematic review. Journal of Psychosomatic Research. 2020;128(March 2019):109866. doi:10.1016/j.jpsychores.2019.109866

15.      Peciña M, Azhar H, Love TM, et al. Personality trait predictors of placebo analgesia and neurobiological correlates. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2013;38(4):639-646. doi:10.1038/npp.2012.227

16.      Jakšic N, Aukst-Margetic B, Jakovljevic M. Does personality play a relevant role in the placebo effect? Psychiatria Danubina. 2013;25(1):17-23.

17.      Geers AL, Helfer SG, Kosbab K, Weiland PE, Landry SJ. Reconsidering the role of personality in placebo effects: Dispositional optimism, situational expectations, and the placebo response. Journal of Psychosomatic Research. 2005;58(2):121-127. doi:10.1016/j.jpsychores.2004.08.011

18. Corsi N, Colloca L. Placebo and Nocebo Effects: The Advantage of Measuring Expectations and Psychological Factors. Frontiers in Psychology. 2017;8(MAR):308. doi:10.3389/fpsyg.2017.00308


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