학술논문
Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial.
Document Type
Academic Journal
Author
Arteaga-Henríquez G; Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; NCRR-The National Center for Register-Based Research, Aahrus University. Aahrus, Denmark. Electronic address: gara.arteaga@vallhebron.cat.; Ramos-Sayalero C; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain.; Ibañez-Jimenez P; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain.; Karina Rosales-Ortiz S; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain.; Kilencz T; Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary.; Schiweck C; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany.; Schnorr I; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany.; Siegl A; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany.; Arias-Vasquez A; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands; Department of Psychiatry, Radboudd University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, the Netherlands.; Bitter I; Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary.; Fadeuilhe C; Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain.; Ferrer M; Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain.; Lavebratt C; Department of Molecular Medicine and Surgery, Karolinska Instituet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.; Matura S; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany.; Reif A; Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany.; Réthelyi JM; Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary.; Richarte V; Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain.; Rommelse N; Karakter Child and Adolescent Psychiatry University Center, Stockholm, the Netherlands.; Antoni Ramos-Quiroga J; Department of Mental Health, Hospital Universitari Vall d́Hebron, Barcelona, Catalonia, Spain; Group of Psychiatry, Mental Health, and Addictions, Vall d́Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain; Biomedical Network Research Center on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autónoma de Barcelona, Barcelona, Catalonia, Spain.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE
Subject
Language
English
Abstract
Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arteaga-Henríquez reported receiving personal fees from Janssen outside the submitted work. Dr. Bitter reported receiving consulting fees from Gedeon Richter and Janssen/Janssen-Cilag; speaker’s honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen/Janssen-Cilag, KRKA, Lundbeck, and Medichem Pharmaceuticals Inc. by Unilab; research grant from Gedeon Richter; royalties from Oxford University Press. Dr. Reif reported receiving personal fees from Medice, Shire/Takeda, SAGE/Biogen, Boehringen Ingelheimm, Janssen, and Cyclerion outside the submitted work. Dr. Ramos-Quiroga reported being on the speakers’ bureau and/or having acted as a consultant for Janssen Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Rafo, received travel awards (air tickets + hotel) from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice for taking part in psychiatric meetings, outside the submitted work. No other disclosures were reported.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arteaga-Henríquez reported receiving personal fees from Janssen outside the submitted work. Dr. Bitter reported receiving consulting fees from Gedeon Richter and Janssen/Janssen-Cilag; speaker’s honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen/Janssen-Cilag, KRKA, Lundbeck, and Medichem Pharmaceuticals Inc. by Unilab; research grant from Gedeon Richter; royalties from Oxford University Press. Dr. Reif reported receiving personal fees from Medice, Shire/Takeda, SAGE/Biogen, Boehringen Ingelheimm, Janssen, and Cyclerion outside the submitted work. Dr. Ramos-Quiroga reported being on the speakers’ bureau and/or having acted as a consultant for Janssen Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Rafo, received travel awards (air tickets + hotel) from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice for taking part in psychiatric meetings, outside the submitted work. No other disclosures were reported.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)