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 Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
BMC Psychiatry. 2021 Jan 5;21(1):4. doi: 10.1186/s12888-020-02992-4.
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.
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/m) 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.
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.
This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.
抗精神病药引起的体重增加（AiWG）是抗精神病药的一种使人虚弱且常见的不良反应。AiWG 会降低预期寿命、生活质量、治疗依从性、患 2 型糖尿病和再入院的可能性。目前，AiWG 的治疗具有挑战性，并且对于最佳治疗策略尚无共识。在这项研究中，我们旨在通过比较二甲双胍与安慰剂在接受常规治疗（包括生活方式干预）的患者中的疗效，来评估二甲双胍治疗 AiWG 的效果。
在这项为期 52 周的随机、双盲、多中心、安慰剂对照、实用性试验中，我们的目标是纳入 256 名超重参与者（BMI>25kg/m），年龄至少 16 岁。如果患者被诊断为精神分裂症谱系障碍，并且使用抗精神病药至少三个月，则有资格参加本研究。参与者将以 1:1 的比例随机分配至安慰剂或二甲双胍组，并接受总计 26 周的治疗。二甲双胍将以 500mg 每日两次开始治疗，并在 2 周后增加至 1000mg 每日两次（最高可达 2000mg 每日）。此外，所有参与者将接受生活方式干预作为常规治疗的一部分，包括运动计划和饮食咨询的组合。主要结局指标是从治疗开始到 26 周治疗期间，与基线相比，两组之间体重的连续变化差异。次要结局指标包括：1）代谢综合征（MetS）的任何元素；2）应答，定义为治疗开始后 26 周时体重减轻≥5%；3）生活质量；4）一般心理健康和身体健康；5）成本效益。最后，我们旨在评估遗传易感性对 BMI 和 MetS 的影响是否有助于估计二甲双胍治疗开始后体重减轻的幅度。
本研究的实用性设计允许比较二甲双胍联合生活方式干预治疗 AiWG 的疗效和安全性，有助于制定关于这一重大健康问题的干预措施指南。
本试验于 2020 年 3 月 8 日在荷兰临床试验注册中心（NTR）在 https://www.trialregister.nl/trial/8440 上进行注册，注册号为 NTR NL8840。
