The NEO-FFI domain of openness to experience moderates ketamine response in treatment resistant depression

There are many putative mechanisms by which ketamine has its effect and many unanswered questions about risks and benefits of long-term ketamine therapy. A research imperative is the identification of predictors of response to intravenous ketamine, especially a sustained response to maintenance ketamine. Temperament is an inherited aspect of personality and is a predictive factor for outcome in treatment resistant depressed (TRD) patients.

We analyzed which domains of personality impacted initial and sustained ketamine response. Utilizing the Neuroticism Extraversion Openness Five Factor Inventory (NEO-FFI) on 125 participants with TRD, we tested (1) whether the degree of neuroticism predicted initial and/or sustained response to ketamine; and (2) whether extraversion, agreeableness, openness to experience, and conscientiousness had an impact on response.

Our findings confirmed previous literature that elevated neuroticism, low conscientiousness, and low extraversion was the pattern of our TRD population regardless of response. Openness was the only factor to significantly predict sustained treatment outcome.

Our findings are limited by the lack of placebo control, small sample size, non- standardized infusion intervals, polypharmacy rather than ketamine monotherapy, a select TRD population in that they had all failed ECT, and a primarily Caucasian population.

Our registry adds to the literature that factors making up temperament may have predictive value in regard to treatment response, specifically the outcome for TRD patients receiving long-term ketamine infusion therapy. If confirmed, assessing for Openness could reduce inappropriate exposure to ketamine with its attendant unknown long-term risks.