Openness to Experience Predicts Response to Ketamine Treatment

man at a therapist
man at a therapist
Researchers examined the effects of temperament on the outcomes of ketamine therapy in treatment resistant depression.

Of 5 potential factors, only openness to experience predicted patient response to ketamine therapy, according to a recent article published in the Journal of Affective Disorders.

In this study, researchers examined the impact of conscientiousness and 4 predictors based on temperament (neuroticism, extroverted, openness to experience, and agreeableness) from the Neuroticism Extroversion Openness Five Factor Inventory (NEO-FFI) on 125 individuals with treatment resistant depression. The researchers quantified associations of factors within the NEO-FFI with varying levels of treatment success. Response to treatment was quantified using the Montgomery-Åsberg Depression Rating Scale.

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Response to ketamine treatment was divided into 3 categories: patients with a sustained response; those with an initial response, and then relapse; and those who were nonresponders. Of the 125 patients, 52 were in the sustained response category, 30 had an initial response, and then others part of a relapse group, while 43 patients were in the no response group. The study population was 93.6% white and 65.6% women.

Researchers used logistic regression to determine which of the NEO-FFI factors predicted response to ketamine therapy. The regression compared the influence of the NEO-FFI factors on 2 comparisons. Only openness to experience was a significant predictor. After accounting for the influence of age, sex, education level, and initial Montgomery-Åsberg Depression Rating score, greater openness to experience was associated with sustained response (P =.045). Patients with a high openness score had significantly greater odds of being in the sustained response group than patients with low openness scores (odds ratio=3.36; 95% CI, 1.26-8.93, P =.015).

The study had major limitations. They include a lack of placebo control, small sample size, individualized rather than standardized infusion intervals, continued outpatient medications instead of ketamine monotherapy, change in the number of acute-phase infusions, and a greater than 90% white study population.

In this first study to examine the effects of temperament on the outcomes of ketamine therapy on patients with treatment resistant depression, openness to experience was the only significant predictor. Study researchers concluded, “If our findings are confirmed, assessing for Openness could reduce inappropriate exposure to ketamine with its attendant unknown risks in the long-term.”


Dale RM, Bryant KA, Finnegan N, et al. The NEO-FFI domain of openness to experience moderates ketamine response in treatment resistant depression. J Affect Disord. 2020;260:323-328.