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.
Basant Pradhan, Ludmil Mitrev, Ruin Moaddell, Irving W. Wainer
Biochimica et biophysica acta. Proteins and proteomics March 18, 2018 DOI: 10.1016/j.bbapap.2018.03.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot randomized placebo-controlled study Pilot study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with post-traumatic stress disorder (PTSD) |
| Interventions | (R S)-ketamine Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER) |
| Dose | single sub-anesthetic dose |
| Topics | Ketamine Meditation PTSD Esketamine |
| Keywords | Humans Pilot projects Double-blind method Stress disorders, post-traumatic Adult Middle aged Female Biomarkers D-serine |
| Citations | 67 |
| Key points | Adding mindfulness-based cognitive therapy (TIMBER) to a single sub-anesthetic dose of (R,S)-ketamine produced a longer duration of therapeutic response than TIMBER plus placebo (34.44 ± 19.12 days vs 16.50 ± 11.39 days, p = 0.022). The authors report that basal plasma d-serine correlated with pre-treatment PTSD severity (r = 0.42, p = 0.07) and that levels at or above 3.5 μM were associated with greater severity and shorter response, suggesting d-serine may be a biomarker and predictor. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Suggests d-serine may serve as a biomarker for clinical response in PTSD patients treated with ketamine infusion and TIMBER psychotherapy.
Synthesized
Comparable studies
Other randomized controlled trials on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Individuals with chronic PTSD | 2021 | Randomized controlled trial | n = 30 |
| Long term structural and functional neural changes following a single infusion of Ketamine in PTSD Individuals diagnosed with PTSD | 2023 | Randomized controlled pilot trial | n = 27 |
| Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol. Veterans with PTSD | 2024 | Randomized controlled trial | n = 100 |
| Combining DNA methylation features and clinical characteristics predicts ketamine treatment response for PTSD. Participants in the CAP-ketamine trial with PTSD | 2026 | Randomized controlled trial |