Abstract: Background　Chronic migraine is prone to be combined with anxiety and depression disorder.But Chinese guidelines for the prevention and treatment of migraine do not specify the treatments for chronic migraine with generalized anxiety disorder.Neurologists or general practitioners choose the treatments of chronic migraine with generalized anxiety disorder according to personal experience or existing drugs in our hospital，and there is no large sample study report in China.Objective　To explore the efficacy and safety of topiramate titration combined with venlafaxine in the treatment of chronic migraine with generalized anxiety disorder.Methods　158 patients with chronic migraine were selected in  the Second Affiliated Hospital of Guangxi Medical University from June 2018 to February 2020.We divided into two groups according to the random number table，one was topiramate group and the other was topiramate combined with venlafaxine group，all of them were treated for 6 months.The attack days，visual analogue scale（VAS），migraine specific quality of life questionnaire（MSQ v2.1），HIT-6，PSQI，HAMA and adverse drug reactions were evaluated before treatment and 3 and 6 months after treatment between two groups.Results　125 patients completed 6 months of treatments and follow-ups，65 cases in topiramate group and 60 cases in topiramate combined with venlafaxine group.There was no interaction between treatment time and treatment method（P>0.05）.Treatment time and treatment method had significant effect on headache attack days，VAS，HIT-6 and PSQI（P<0.05）.After 3 months of treatment，the headache attack days，VAS，HIT-6，PSQI and MSQ V2.1 total scores of the two groups decreased compared with those before treatment（P<0.05）.After 6 months of treatment，the attack days and PSQI in topiramate group were less than those in the same group for 3 months，while the attack days，VAS，HIT-6 and PSQI in the topiramate combined with venlafaxine group were less than those in the same group for 3 months（P<0.05）.After 6 months of treatment，the headache attack days，VAS，HIT-6 of topiramate combined with venlafaxine group were less than those of topiramate group（P<0.05）.There was no interaction between treatment time and treatment method（P>0.05）.Treatment time and treatment method had significant effect on MSQ v2.1 function limitation，function loss，emotional function and total score was significant（P<0.05）.MSQ v2.1 function limitation，function loss，emotional function and total score of the two groups were lower than those before treatment after 3 months of treatment（P<0.05）.After 6 months of treatment，the function limitation，function loss，emotional function and total score of topiramate combined with venlafaxine group were lower than those of the same group for 3 months（P<0.05）.After 6 months of treatment，the function limitation，function loss，emotional function and total score of topiramate combined with venlafaxine group were lower than those of topiramate group（P<0.05）.The effective rate of topiramate combined with venlafaxine group was higher than that of topiramate group at 3 and 6 months（P<0.05）.There were 114 patients with oral topiramate dose of 100 mg/D，accounting for 79.78%（71/89） of the total effective number；18 patients with 150 mg / D accounted for 20.22%（18/89）.There was no significant difference in the incidence of adverse drug reactions between the two groups（χ2=0.170，P=0.680）.Conclusion　Topiramate combined with venlafaxine is safe and effective in the treatment of chronic migraine with generalized anxiety disorder.

Key words: Migraine disorders, Anxiety, Topiramate, Venlafaxine, Treatment outcome

摘要： 背景　慢性偏头痛易合并焦虑抑郁障碍，我国偏头痛防治指南未明确慢性偏头痛伴广泛性焦虑障碍的治疗方案。临床医生根据个人经验或者本医院现有药物选择慢性偏头痛伴广泛性焦虑障碍的治疗方案，且国内无相关大样本研究报道。目的　探讨托吡酯滴定疗法联合文拉法辛治疗慢性偏头痛伴广泛性焦虑障碍患者的临床疗效、安全性及托吡酯有效剂量。方法　选取2018年6月—2020年2月于广西医科大学第二附属医院就诊的慢性偏头痛伴广泛性焦虑障碍患者158例，按照随机数字表法分为托吡酯组79例和托吡酯联合文拉法辛组79例。两组均给予托吡酯片治疗，托吡酯联合文拉法辛组在此基础上给予盐酸文拉法辛缓释胶囊治疗，均治疗6个月。分别评定治疗前及治疗3、6个月两组患者头痛发作天数、头痛严重程度视觉模拟评分（VAS）、特异性生活质量问卷（MSQ V2.1）评分、头痛影响测定-6（HIT-6）评分、匹兹堡睡眠质量指数（PSQI）评分、汉密尔顿焦虑量表（HAMA）评分和药物不良反应。结果　最终完成6个月治疗及随访患者共125例：托吡酯组65例，托吡酯联合文拉法辛组60例。治疗时间与治疗方法无交互作用（P>0.05），治疗时间、治疗方法在头痛发作天数、VAS、HIT-6评分和PSQI评分上主效应显著（P<0.05）；治疗3个月两组患者头痛发作天数、VAS、HIT-6评分和PSQI评分均少于同组治疗前（P<0.05）；治疗6个月托吡酯组头痛发作天数、PSQI评分少于同组治疗3个月，托吡酯联合文拉法辛组头痛发作天数、VAS、HIT-6评分和PSQI评分少于同组治疗3个月（P<0.05）；治疗6个月托吡酯联合文拉法辛组头痛发作天数、VAS、HIT-6评分少于托吡酯组（P<0.05）。治疗时间与治疗方法无交互作用（P>0.05），治疗时间、治疗方法在MSQ V2.1功能限制、功能丧失、情感功能评分及总分上主效应显著（P<0.05）；治疗3个月两组患者MSQ V2.1功能限制、功能丧失、情感功能评分及总分低于同组治疗前（P<0.05）。治疗6个月托吡酯联合文拉法辛组MSQ V2.1功能限制、功能丧失、情感功能评分及总分低于同组治疗3个月（P<0.05）。治疗6个月托吡酯联合文拉法辛组MSQ V2.1功能限制、功能丧失、情感功能评分及总分低于托吡酯组（P<0.05）。治疗3、6个月托吡酯联合文拉法辛组的总有效率均高于托吡酯组（P<0.05）。托吡酯口服剂量100 mg/d患者114例，占总有效人数的比例为79.78%（71/89）；150 mg/d患者18例，占总有效人数的比例为20.22%（18/89）。两组药物不良反应发生率比较，差异无统计学意义（χ2=0.170，P=0.680）。结论　托吡酯联合文拉法辛治疗慢性偏头痛伴广泛性焦虑障碍可减少患者头痛发作天数，减轻偏头痛疼痛程度，改善患者睡眠，提高患者生活质量；托吡酯应用剂量100 mg/d时效果可能较好。

关键词: 偏头痛, 焦虑, 托吡酯, 文拉法辛, 治疗结果