d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study

Abstract

Post-traumatic stress disorder (PTSD) is a chronic and debilitating condition that is often refractory to standard frontline antidepressant therapy. A promising new approach to PTSD therapy is administration of a single sub-anesthetic dose of (R,S)-ketamine (Ket). The treatment produces rapid and significant therapeutic response, which lasts for only 4-7 days. In one of our studies, the mean duration of response was increased to 33 days when Ket administration was combined with a mindfulness-based cognitive therapy, Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER). We now report the results from a 20-patient study, which examined the duration of sustained response with combined TIMBER-Ket therapy, TIMBER-K arm, relative to the response observed in a placebo-controlled arm, TIMBER-P. A significant difference in the duration of response was observed between TIMBER-K and TIMBER-P arms: 34.44 ± 19.12 days and 16.50 ± 11.39 days, respectively (p = 0.022). Previous studies identified a negative correlation between antidepressant response to Ket and basal plasma concentrations of d-serine (DSR). In this study, the basal DSR levels positively correlated with the pre-treatment severity of PTSD symptoms (Pearson's r = 0.42, p = 0.07) and patients with basal DSR level ≥ 3.5 μM displayed not only higher PTSD severity but also shorter duration of response. The data indicate that basal DSR levels may serve as a biomarker of the severity of PTSD symptoms and as a predictor of clinical response. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

Keywords: Ketamine; Mindfulness; PTSD; d-Serine.

Conflict of interest statement

Conflicts of interest

The authors declare that there are no conflicts of interest.

Copyright © 2018 Elsevier B.V. All rights reserved.

Figures

Fig. 1

A. The distribution of patients according to basal D-serine plasma concentrations using 3.5 μM as the cutoff between “high” and “normal” concentrations where the subjects in the Timber-K arm of the are denoted in blue and the subjects in the TIMBER-P arm are denoted in red. B. The changes in the D-serine plasma concentrations at the conclusion of the 40-min intra venous infusion where the subjects receiving a 0.5 mg/kg dose of (R,S)-ketamine (K) are denoted in red and the subjects receiving normal saline (P) are denoted in blue and where basal plasma concentrations of D-serine are indicated by open circles (○) and the 40-min concentrations by filled circles (●).

Fig. 2

The distribution of basal D-serine plasma concentrations using the data from 21 patients with treatment resistant depression [20] and the 19 subjects in this study where the basal DSR plasma concentrations are grouped into 1 μM divisions (x axis) and the number of subjects within each division are presented (y axis).