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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

Effects of Repeated Intravenous Ketamine in Treatment-Resistant Geriatric Depression: A Case Series.

PURPOSE: There is an immediate need for more sustainable, effective therapies for treatment-resistant depression in patients who do not respond to traditional psychopharmacology. The aim of this study was to determine the efficacy and safety of intravenous ketamine infusions on the elderly population by using a case series of 6 geriatric patients with treatment-resistant depression. METHODS: Eligible patients aged 65 to 82 were given a subanesthetic ketamine hydrochloride dose of 0.5 mg/kg delivered intravenously over 40 minutes twice weekly for an acute series. If patients reported a 50% decrease in depression symptoms after the acute series of 2 to 4 infusions, they would be moved to a maintenance series of infusions, which would occur every 2 to 6 weeks on an individual basis. RESULTS: Of the 6 patients given ketamine, 1 failed to respond to the acute treatment phase, 4 responded to the acute infusion phase but failed to sustain a response after a range of 8 to 22 maintenance infusions, and 1 responded to the infusions but relapsed into alcohol use; therefore, treatment was discontinued. CONCLUSIONS: The relative safety of intravenous ketamine in the elderly was demonstrated by the mild, transient adverse effects seen by this patient group. The geriatric population is unable to maintain an antidepressant response to intravenous ketamine over time, signifying that ketamine has low efficacy for the elderly.

A 12-month naturalistic observation of three patients receiving repeat intravenous ketamine infusions for their treatment-resistant depression.

BACKGROUND: Acute administration of subanesthestic doses of intravenous ketamine have been shown to elicit a rapid antidepressant response in patients with treatment-resistant depression. However, it remains to be seen if repeated doses over a longer period of time will have the same effects. Here, we assess the long-term efficacy of repeated intravenous ketamine infusions in three patients with high treatment-resistant depression via a naturalistic observation study. METHOD: Three patients consented to intravenous ketamine infusions as a therapy for their treatment-resistant depression. Patients were administered ketamine at 0.5mg/kg of ideal body weight over 40 min followed by a saline flush until discharge. Severity of depressive symptoms was rated with the Montgomery-Asberg Depression Rating Scale. RESULTS: All three patients responded to the ketamine infusions, but each went through an individualized course of treatment based on their own response. LIMITATIONS: This was an open-label naturalistic observation without blinding, randomization, or a placebo control. CONCLUSIONS: These cases add to the literature supporting the therapeutic effect of low-dose repeated intravenous ketamine for patients with treatment-resistant depression. Further study is needed to define the risks, benefits, indications, and contraindications of this potential treatment.