Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 5;21(1):4.
doi: 10.1186/s12888-020-02992-4.

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

Nini de Boer  1 , Sinan Guloksuz  2   3 , Caroline van Baal  4 , Leonie Willebrands  5 , Jeroen Deenik  5   2   6 , Christiaan H Vinkers  7   8 , Inge Winter-van Rossum  5 , Janneke Zinkstok  5 , Ingeborg Wilting  9 , Jasper B Zantvoord  7 , Frank Backx  10 , Wilma E Swildens  11   12 , Marieke Schouw  11 , Jan Bogers  13 , Folkwin Hulshof  14 , Rudolf de Knijff  14 , Peter Duindam  14 , Mike Veereschild  14 , Maarten Bak  2   15 , Geert Frederix  16 , Lieuwe de Haan  7   17 , Jim van Os  5   2   18 , Wiepke Cahn  5   11 , Jurjen J Luykx  5   14   19
Affiliations

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

Nini de Boer et al. BMC Psychiatry. .

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: In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) 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.

Keywords: Antipsychotic-induced weight gain (AiWG); Lifestyle; Metformin; Schizophrenia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance. Am J Psychiatry. 2004;161(2):361–363. doi: 10.1176/appi.ajp.161.2.361. - DOI - PMC - PubMed
    1. Pillinger T, Mccutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020. 10.1016/S2215-0366(19)30416-X. - PMC - PubMed
    1. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and Management of the Metabolic Syndrome. Circulation. 2005;112(17):2735–2752. doi: 10.1161/CIRCULATIONAHA.105.169404. - DOI - PubMed
    1. Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001;62(Suppl 7):22–31. - PubMed
    1. Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68(Suppl 1):20–27. - PubMed

Publication types

LinkOut - more resources