Battini Vera, Cirnigliaro Giovanna, Leuzzi Rodolfo, Rissotto Eleonora, Mosini Giulia, Benatti Beatrice, Pozzi Marco, Nobile Maria, Radice Sonia, Carnovale Carla, Dell'Osso Bernardo, Clementi Emilio
Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy.
Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy.
Front Psychiatry. 2023 Jul 12;14:1215807. doi: 10.3389/fpsyt.2023.1215807. eCollection 2023.
Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.
We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.
A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.
Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
二甲双胍在治疗精神分裂症或分裂情感性障碍患者的抗精神病药物所致代谢综合征（MetS）方面已显示出良好疗效。其诱导抗抑郁行为效应和改善认知功能的能力也已得到研究，但相关信息尚未系统化。因此，本研究旨在通过系统评价和荟萃分析，探讨二甲双胍对接受抗精神病药物治疗的精神分裂症患者认知及其他症状维度的影响。
我们检索了截至2022年2月的PubMed、ClinicalTrials.Gov、Embase、PsycINFO和WHO ICTRP数据库，纳入评估诊断为精神分裂症及相关障碍患者的随机对照试验（RCT），这些患者接受二甲双胍作为抗精神病药物的附加治疗以治疗体重增加，并评估了精神症状和认知功能的变化。
共有19项RCT符合纳入标准。对12项符合条件的研究进行了荟萃分析。我们发现，病情稳定的精神分裂症患者在治疗24周后有积极趋势[标准化均数差（95%置信区间）=-0.40（-0.82；0.01），比值比（95%置信区间）=0.5（-2.4；3.4）]。在精神分裂症认知简短评估量表和阳性与阴性症状量表（PANSS）中检测到更好的表现，各研究间异质性较低。一项研究报告，BACS语言记忆子域的变化有利于安慰剂组[平均差（95%置信区间）=-16.03（-23.65；8.42）]。胃肠道疾病、口干和锥体外系综合征是报告最多的不良反应。还描述了精神科不良事件：特别是可归因于精神分裂症复发的症状。
发现二甲双胍在改善精神分裂症患者的认知及其他症状维度方面有一定程度的疗效。鉴于这种潜在药理作用的临床相关性，强烈建议使用适当心理测量量表进行更长时间的专门研究。同样，需要评估二甲双胍在此背景下的作用方式，以提高其疗效或找到更有效的药物。
