P11 (S100A10) as a potential predictor of ketamine response in patients with SSRI-resistant depression

Veldman, Emma R.; Mamula, Dejan; Jiang, Hanyang; Tiger, Mikael; Ekman, Carl Johan; Lundberg, J.; Svenningsson, Per

doi:10.1016/j.jad.2021.04.055

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…Moderator analyses may yield smaller effect sizes, necessitating larger samples, and rely on sufficient heterogeneity within study participants. Although some predictors of ketamine’s antidepressant efficacy, including clinical (e.g., family history of alcohol use disorder [ 7 , 8 ]; suicide history [ 9 ]; body mass index (BMI) [ 9 ]; benzodiazepine use [ 10 ]) and mechanistic (e.g., neuroimaging [ 11 – 13 ]; cognitive [ 14 ]; peripheral blood markers [ 15 , 16 ]; genetic [ 17 , 18 ]) variables, have been reported, none have been replicated across more than one RCT [ 19 , 20 ]. RCT designs are essential to separate specific from non-specific predictors of outcome, but many predictive analyses have been conducted in ketamine-treated patients alone.…”

Section: Introductionmentioning

confidence: 99%

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

et al. 2022

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Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630

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Section: Introductionmentioning

confidence: 99%

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

et al. 2022

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“…Protein p11 has been noted to be involved in the pathophysiology of mood disorders, as well as in the ketamine mechanism of action, and has been suggested to be a biomarker of response to therapy with also other antidepressants [ 82 ]. The only study found that addressed the predictive role of p11 in TRD response was conducted by Veldman et al [ 65 ]. This study investigated baseline p11 levels in association with the responses of 30 patients resistant to SSRIs given 0.5 mg/kg i.v.…”

Section: Peripheral Prognostic Biomarkers In Trd Treatmentmentioning

confidence: 99%

Prognostic Significance of Blood-Based Baseline Biomarkers in Treatment-Resistant Depression: A Literature Review of Available Studies on Treatment Response

et al. 2022

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Major depressive disorder is a leading cause of disability worldwide and a major contributor to the overall global burden of disease. While there are several options for antidepressant treatment, only about 40–60% of patients respond to initial monotherapy, while 30–40% of patients may even show resistance to treatment. This article offers a narrative review of those studies evaluating the predictive properties of various blood-based baseline biomarkers regarding treatment responses to the pharmacological, stimulation, or behavioral treatment of patients with treatment-resistant depression (TRD). Our results show that overall, there is only a very limited number of studies assessing baseline peripheral biomarkers regarding treatment response in TRD. Although there is some evidence for the predictive significance of particular biomarkers (e.g., IL-6, CRP, BDNF), the majority of the results are either single-study reports or studies with conflicting results. This may contribute to the wide variety of treatment protocols and different TRD definition criteria, the small number of patients included, and the existence of different biological phenotypes of the disorder used within the various studies. Taken together, there does not yet appear to be any specific baseline peripheral biomarker with sufficient discriminative predictive validity that can be used in the routine clinical practice of TRD. The discovery of new biomarkers and the better clinical characterization of known biomarkers could support the better classification and staging of TRD, the development of personalized treatment algorithms with higher rates of remission and fewer side effects, and the development of new precision drugs for specific subgroups of patients.

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“…Τα αποτελέσματα έδειξαν πως υψηλότερα επίπεδα αναφοράς της πρωτεΐνης p11 στα κυτταροτοξικά Τλεμφοκύτταρα στην περιφέρεια συσχετίστηκαν σημαντικά με την ανταπόκριση στη θεραπεία με κεταμίνη. 80 β. D-σερίνη Η D-σερίνη είναι ένας ενδογενής συναγωνιστής του υποδοχέα NMDA με ειδική συγγένεια με τη θέση γλυκίνης, που παίζει βασικό ρόλο στη NMDA νευροδιαβίβαση και νευροπλαστικότητα. Σε 21 ασθενείς με TRD, οι Moaddel et al έδειξαν ότι οι συγκεντρώσεις αναφοράς D-σερίνης στο πλάσμα υπό κεταμίνη ήταν πολύ χαμηλότερες στους ανταποκρινόμενους σε σύγκριση με τους μη ανταποκρινόμενους, ενώ χαμηλότερες αρχικές συγκεντρώσεις D-σερίνης στο πλάσμα προέβλεπαν αντικαταθλιπτική ανταπόκριση στην κεταμίνη, με τη D-σερίνη αναφοράς να εξηγεί το 60% της διακύμανσης της κλινικής απόκρισης.…”

Section: άλλοι βιοδείκτες α πρωτεΐνη P11unclassified

Peripheral prognostic biomarkers of response in treatment-resistant depression

Agorastos¹,

Gkesoglou²,

Kleidonopoulos³

et al. 2021

Psychiatriki

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P11 (S100A10) as a potential predictor of ketamine response in patients with SSRI-resistant depression

Cited by 5 publications

References 15 publications

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

Prognostic Significance of Blood-Based Baseline Biomarkers in Treatment-Resistant Depression: A Literature Review of Available Studies on Treatment Response

Peripheral prognostic biomarkers of response in treatment-resistant depression

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