Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial
BMC Psychiatry, vol. 21, pp. 4
Abstract
BACKGROUND: Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. METHODS: ) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. DISCUSSION: The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. TRIAL REGISTRATION: This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.
Authors 24
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Nini de Boer corresponding
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands. N.M.deBoer-6@umcutrecht.nl
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
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Maastricht University Medical Centre · Yale University
Affiliation as printed
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Biostatistics and Research Support, Julius Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
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Utrecht University · Maastricht University Medical Centre · University Medical Center Utrecht · GGz centraal
Affiliation as printed
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
GGz Centraal Mental Health, Amersfoort, The Netherlands
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GGZ inGeest · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
GGZinGeest Mental Health, Amsterdam, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Rehabilitation, Physiotherapy Science & Sport, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Altrecht GGZ · Inholland University of Applied Sciences
Affiliation as printed
Altrecht Mental Health Care Institute, Utrecht, The Netherlands
Inholland University of Applied Sciences, Interprofessional Mental Health Care, department Nursing, Amsterdam, The Netherlands
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Affiliation as printed
Altrecht Mental Health Care Institute, Utrecht, The Netherlands
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Affiliation as printed
GGZ Rivierduinen, Oegstgeest, The Netherlands
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Affiliation as printed
GGNet Mental Health, Warnsveld, The Netherlands
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Affiliation as printed
GGNet Mental Health, Warnsveld, The Netherlands
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Affiliation as printed
GGNet Mental Health, Warnsveld, The Netherlands
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Affiliation as printed
GGNet Mental Health, Warnsveld, The Netherlands
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Maastricht University Medical Centre
Affiliation as printed
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands
Mondriaan Mental Health, Maastricht, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Public Health, Julius Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Arkin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Arkin GGZ, Amsterdam, The Netherlands
Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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King's College London · Utrecht University · Maastricht University Medical Centre · University Medical Center Utrecht
Affiliation as printed
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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Utrecht University · University Medical Center Utrecht · Altrecht GGZ
Affiliation as printed
Altrecht Mental Health Care Institute, Utrecht, The Netherlands
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
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Utrecht University · University Medical Center Utrecht · GGNet
Affiliation as printed
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
GGNet Mental Health, Warnsveld, The Netherlands
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