PMID- 30784233 OWN - NLM STAT- MEDLINE DCOM- 20200309 LR - 20200309 IS - 1751-7893 (Electronic) IS - 1751-7885 (Linking) VI - 13 IP - 6 DP - 2019 Dec TI - Multimodal prevention of first psychotic episode through N-acetyl-l-cysteine and integrated preventive psychological intervention in individuals clinically at high risk for psychosis: Protocol of a randomized, placebo-controlled, parallel-group trial. PG - 1404-1415 LID - 10.1111/eip.12781 [doi] AB - AIM: Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects. METHODS: In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities. RESULTS: This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 x 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months. CONCLUSION: This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions. CI - (c) 2019 John Wiley & Sons Australia, Ltd. FAU - Schmidt, Stefanie J AU - Schmidt SJ AD - Department of Clinical Psychology and Psychotherapy, University of Bern, Bern, Switzerland. AD - University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. FAU - Hurlemann, Rene AU - Hurlemann R AD - Department of Psychiatry, University Hospital Bonn, Bonn, Germany. AD - Division of Medical Psychology, University Hospital Bonn, Bonn, Germany. FAU - Schultz, Johannes AU - Schultz J AD - Department of Psychiatry, University Hospital Bonn, Bonn, Germany. AD - Division of Medical Psychology, University Hospital Bonn, Bonn, Germany. FAU - Wasserthal, Sven AU - Wasserthal S AD - Department of Psychiatry, University Hospital Bonn, Bonn, Germany. AD - Division of Medical Psychology, University Hospital Bonn, Bonn, Germany. FAU - Kloss, Christian AU - Kloss C AD - Department of Psychiatry, University Hospital Bonn, Bonn, Germany. AD - Division of Medical Psychology, University Hospital Bonn, Bonn, Germany. FAU - Maier, Wolfgang AU - Maier W AD - Department of Psychiatry, University Hospital Bonn, Bonn, Germany. AD - German Center for Neurodegenerative Diseases, Bonn, Germany. FAU - Meyer-Lindenberg, Andreas AU - Meyer-Lindenberg A AD - Central Institute of Mental Health, Mannheim, Germany. FAU - Hellmich, Martin AU - Hellmich M AD - Institute of Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany. FAU - Muthesius-Digon, Ana AU - Muthesius-Digon A AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. FAU - Pantel, Tanja AU - Pantel T AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. FAU - Wiesner, Pia-Sophie AU - Wiesner PS AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. FAU - Klosterkotter, Joachim AU - Klosterkotter J AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. FAU - Ruhrmann, Stephan AU - Ruhrmann S AD - Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. CN - ESPRIT-B1 Group LA - eng GR - 01EE1407C/Bundesministerium fur Bildung und Forschung/International GR - 01EE14071/Bundesministerium fur Bildung und Forschung/International PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190219 PL - Australia TA - Early Interv Psychiatry JT - Early intervention in psychiatry JID - 101320027 RN - 0 (Antipsychotic Agents) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*therapeutic use MH - Adolescent MH - Adult MH - Antipsychotic Agents/therapeutic use MH - *Cognitive Behavioral Therapy MH - Combined Modality Therapy/methods MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Multicenter Studies as Topic MH - Psychotic Disorders/*drug therapy/*prevention & control/psychology/*therapy MH - Randomized Controlled Trials as Topic/*methods MH - Single-Blind Method MH - Stress, Psychological/complications/drug therapy/therapy MH - Young Adult OTO - NOTNLM OT - N-acetyl-l-cysteine OT - clinical high risk OT - cognitive remediation OT - prevention OT - psychosis OT - social cognition FIR - Bechdolf, A IR - Bechdolf A FIR - Brockhaus-Dumke, A IR - Brockhaus-Dumke A FIR - Hirjak, D IR - Hirjak D FIR - Fallgatter, A IR - Fallgatter A FIR - Frieling, H IR - Frieling H FIR - Janssen, B IR - Janssen B FIR - Jessen, F IR - Jessen F FIR - Kambeitz, J IR - Kambeitz J FIR - Koutsouleris, N IR - Koutsouleris N FIR - Leopold, K IR - Leopold K FIR - Schafer, C IR - Schafer C FIR - Schultze-Lutter, F IR - Schultze-Lutter F FIR - Striepens, N IR - Striepens N FIR - Vernaleken, I IR - Vernaleken I FIR - Walter, H IR - Walter H FIR - Wildgruber, D IR - Wildgruber D EDAT- 2019/02/21 06:00 MHDA- 2020/03/10 06:00 CRDT- 2019/02/21 06:00 PHST- 2018/05/16 00:00 [received] PHST- 2018/09/27 00:00 [revised] PHST- 2018/12/26 00:00 [accepted] PHST- 2019/02/21 06:00 [pubmed] PHST- 2020/03/10 06:00 [medline] PHST- 2019/02/21 06:00 [entrez] AID - 10.1111/eip.12781 [doi] PST - ppublish SO - Early Interv Psychiatry. 2019 Dec;13(6):1404-1415. doi: 10.1111/eip.12781. Epub 2019 Feb 19.