Center for Drug Safety Studies (CESME), University of Valladolid, Ramon y Cajal Avenue, 7, 47005, Valladolid, Spain.
Pharmacogenetics, Cancer Genetics, Genetic Polymorphisms and Pharmacoepidemiology Research Group, University of Valladolid, Valladolid, Spain.
Sci Rep. 2021 Jul 27;11(1):15304. doi: 10.1038/s41598-021-94700-9.
Weight gain is a frequent and severe adverse reaction in patients taking antipsychotics. The objective was to further investigate in a natural setting influential risk factors associated with clinically significant weight gain. An observational follow-up study was conducted. Patients when initiating treatment with whatever antipsychotic were included; a structured questionnaire was applied at baseline, 3 and 6 months later; a blood sample was obtained. In a nested case-control approach, patients with an increase ≥ 7% of their initial weight were considered as cases, the remaining, as controls. The results showed that, out of 185 patients, 137 completed the 6-month follow-up (cases, 38; controls, 99). Weight gain gradually and significantly increased in cases (baseline, 65.0 kg; 6 months, 74.0 kg) but not in controls (65.6 kg and 65.8 kg, respectively). Age (adjusted OR = 0.97, 95% CI = 0.96-0.99, p = 0.004), olanzapine (adjusted OR = 2.98, 95% CI = 1.13-7.80, p = 0.027) and quetiapine (adjusted OR = 0.25, 95% = 0.07-0.92, p = 0.037) significantly associated with weight gain. An association was also found for the CNR1 (rs1049353) and INSIG2 (rs7566605) polymorphisms. In conclusion, an increased risk of antipsychotics-induced weight gain was observed for younger age and olanzapine, and a relative lower risk for quetiapine. A potential role of CNR1 rs1049353 and INSIG2 rs7566605 polymorphisms is suggested.
体重增加是服用抗精神病药物的患者常见且严重的不良反应。本研究旨在自然环境下进一步探究与临床显著体重增加相关的影响因素。这是一项观察性随访研究。纳入起始使用任何一种抗精神病药物治疗的患者；在基线、3 个月和 6 个月时应用结构化问卷进行调查；并采集血样。采用巢式病例对照研究，体重增加≥初始体重的 7%的患者为病例，其余为对照。结果显示，在 185 例患者中，有 137 例完成了 6 个月的随访（病例 38 例，对照 99 例）。病例组体重逐渐显著增加（基线时 65.0kg，6 个月时 74.0kg），但对照组无显著变化（分别为 65.6kg 和 65.8kg）。年龄（校正比值比 0.97，95%可信区间 0.96-0.99，p=0.004）、奥氮平（校正比值比 2.98，95%可信区间 1.13-7.80，p=0.027）和喹硫平（校正比值比 0.25，95%可信区间 0.07-0.92，p=0.037）与体重增加显著相关。CNR1(rs1049353)和 INSIG2(rs7566605)多态性也与体重增加相关。总之，年龄较小和使用奥氮平与抗精神病药物引起的体重增加风险增加相关，而使用喹硫平的风险相对较低。提示 CNR1(rs1049353)和 INSIG2(rs7566605)多态性可能起作用。
