Exercise as an add-on treatment in individuals with schizophrenia: Results from a large multicenter randomized controlled trial.

Current treatment methods do not achieve recovery for most individuals with schizophrenia, and symptoms such as negative symptoms and cognitive deficits often persist. Aerobic endurance training has been suggested as a potential add-on treatment targeting both physical and mental health. We performed a large-scale multicenter, rater-blind, parallel-group randomized controlled clinical trial in individuals with stable schizophrenia. Participants underwent a professionally supervised six-month training comprising either aerobic endurance training (AET) or flexibility, strengthening, and balance training (FSBT, control group), follow-up was another six months. The primary endpoint was all-cause discontinuation (ACD); secondary endpoints included effects on psychopathology, cognition, functioning, and cardiovascular risk. In total, 180 participants were randomized. AET was not superior to FSBT in ACD and most secondary outcomes, with dropout rates of 59.55% and 57.14% in the six-month active phase, respectively. However, both groups showed significant improvements in positive, general, and total symptoms, levels of functioning and in cognitive performance. A higher training frequency additionally promoted further memory domains. Participants with higher baseline cognitive abilities were more likely to respond to the interventions. Our results support integrating exercise into schizophrenia treatment, while future studies should aim to develop personalized training recommendations to maximize exercise-induced benefits.

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Copyright © 2023. Published by Elsevier B.V.

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Declaration of Competing Interest AS: honorary speaker for TAD Pharma and Roche, member of Roche advisory boards. AH: editor of the German (DGPPN) schizophrenia treatment guidelines, first author of the WFSBP schizophrenia treatment guidelines; on advisory boards of and speaker fees from AbbVie (speaker fees only), Advanz (speaker fees only), Janssen-Cilag, Lundbeck, Recordati, Rovi, and Otsuka. PF: co-editor of the German (DGPPN) schizophrenia treatment guidelines, co-author of the WFSBP schizophrenia treatment guidelines; on advisory boards and speaker fees from Janssen, Lundbeck, Otsuka, Servier, and Richter. AML: consultant fees from Boehringer Ingelheim, Elsevier, Brainsway, Lundbeck Int. Neuroscience Foundation, Lundbeck A/S, Sumitomo Dainippon Pharma Co., Academic Medical Center of the University of Amsterdam, Synapsis Foundation-Alzheimer Research Switzerland, IBS Center for Synaptic Brain Dysfunction, Blueprint Partnership, University of Cambridge, Dt. Zentrum für Neurodegenerative Erkrankungen, Zürich University, Brain Mind Institute, L.E.K. Consulting, ICARE Schizophrenia, Science Advances, Fondation FondaMental, v Behring Röntgen Stiftung, The Wolfson Foundation, and Sage Therapeutics; speaker fees from Lundbeck International Foundation, Paul-Martini-Stiftung, Lilly Deutschland, Atheneum, Fama Public Relations, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Janssen-Cilag, Hertie Stiftung, Bodelschwingh-Klinik, Pfizer, Atheneum, University of Freiburg, Schizophrenia Academy, Hong Kong Society of Biological Psychiatry, Fama Public Relations, Spanish Society of Psychiatry, Italian Society of Biological Psychiatry, Reunions I Ciencia S.L., and Brain Center Rudolf Magnus UMC Utrecht; awards from the Prix Roger de Spoelberch grant and the CINP Lilly Neuroscience Clinical Research Award 2016. IM, LR, ML, IP, DG, SMu, EW, MC, RS, TSA, KR, MH, ES, ET, BV, CHa, SMo, CHu, AR, KKV, BM, HW, BW, WW, KH, and DH report no conflicts of interest.