二甲双胍对奥氮平所致精神分裂症患者体质量增加的影响

Metformin addition therapy attenuates olanzapine-induced weight gain

目的验证二甲双胍预防奥氮平引起精神分裂症患者的体质量增加和糖代谢紊乱的效果。方法将37例未服过抗精神病药的精神分裂症患者，随机分为奥氮平（15mg／d）联合二甲双胍组（750mg／d；A组，18例）和奥氮平（15mg／d）联合安慰剂组（B组，19例），治疗12周。于治疗前和治疗第4周末、8周末及12周末测定空腹血糖、胰岛素（INS）、身高、体质量、腰围、臀围，计算体质量指数（BMI）、腰臀比（WHR）、胰岛素抵抗指数（IRI）及治疗12周末体质量增加大于7％的比率。用阳性症状量表（SAPS）、阴性症状量表（SANS）于治疗前和治疗12周末评定疗效。结果治疗12周末，A、B两组的体质量、BMI、WHR及B组患者的空腹INS和IRI较治疗前均升高（P〈0．05）。治疗第8，12周末，B组的体质量、BMI、空腹INS和IRI的变化值高于A组（P〈0．05）。B组体质量增加大于7％的比率（63％，12例）高于A组（17％，3例；尸〈0．01）。A、B两组的SAPS及SANS评分均显著低于治疗前（均P〈0．05），但组间差异均无统计学意义（P〉0．05）。结论二甲双胍能有效减轻奥氮平引起的体质量增加和糖代谢紊乱。

Objective The purpose of this study was to assess the efficacy of mefformin in preventing olanzapine-induced weight gain and glucose metabolic dysfunction. Methods In the 12 week placebo-controlled study, 37 drug-naive schizophrenic patients were randomly divided into two treatment groups, one with olanzapine （15 mg/d） plus mefformin （750 mg/d） （n = 18）, one with olanzapine （15 mg/d） plus placebo （n = 19 ）. The body weight, body mass index （BMI）, waist circumference, hip circumference, waist-hip-ratio （WHR）, fasting glucose and insulin, insulin resistance index （IRI） was measured. The symptom was assessed with the Scale for the Assessment of Positive Symptoms （SAPS） and Scale for the Assessment of Negative Symptoms （SANS）. Results There was a significant increase in body weight and BMI within each group from baseline to week 12 [ mefformin group of （ 1.90 ± 2.72 ） kg and （0. 54 ±0. 92） kg/m^2 ; placebo group of （6. 87 ±4. 23） kg and （2. 26 ± 1.12） kg/m^2 ] （P 〈0.05）. The increase in weight, BMI, WHR, insulin and IRI values in placebo group was more than that in mefformin group （P 〈 0.05 ）. The lower rate of weight increase of more than 7% from baseline to 12 week was in mefformin group than in placebo group （ 17% vs. 63% ; P 〈 0.01 ） . Conclusion Mefformin addition therapy is effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drugnaive schizophrenia patients.