81例短期初次使用苯二氮类药物的撤药观察

Observation Of Withdrawal Process Of 81 Cases First Treated With Benzodiazepines For Short-term : A Prospective Cohort Study

目的:观察、比较短期(4-6周)初次使用苯二氮类的撤药过程,为合理应用苯二氮类药物(BZDs)提供一些参考。方法:本研究为前瞻性队列研究。选取连续使用5羟色胺再摄取抑制剂(SSRIs)+BZDs方案治疗4-6周临床痊愈的初诊初治广泛性焦虑障碍(GAD)患者共81名,按BZDs分组(劳拉西泮41人,使用氯硝西泮组40人)。在自愿情况下,进行苯二氮卓类药物撤药(撤药时BZDs均为0.5mg/天),用汉密尔顿焦虑量表(HAMA-14)评定撤药过程中焦虑反应最严重时的焦虑水平,用t检验或χ2检验比较撤药前后两组患者HAMA得分情况、撤药症状的发生率等方面的差异。结果:两组患者在撤药后HAMA评分均增高(P<0.01);组间对比,在HAMA总分、精神性焦虑、害怕、失眠、撤药症状发生率等方面,氯硝西泮组均高于劳拉西泮组。结论:4-6周短期连续使用BZDs可出现撤药症状;氯硝西泮组撤药后焦虑水平较劳拉西泮组高,其中失眠、精神焦虑更突出。更短期或按需使用BZDs,优先选择短效低亲和力的BZDs药物,可能有助于减轻撤药症状、减少依赖的产生。

Objective： To observe and compare the withdrawal process after being treated with clonazepam or lorazepam for short-term （4-6 weeks）, and provide some references for rationally using BZDs. Methods： In this prospective cohort study, 81 patients who were diagnosed with generalized anxiety disorder in first time according to ICD-10 and never treated before were selected. All the patients were clinically cured with 5 selective serotonin reuptake inhibitors （SSRIs） plus BZDs consecutively within 4-6 weeks. According the type of BZDs, patients were divided into two groups： lorazepam group （n=41） and clonazepam group （n=40）. Each patient voluntarily stop using the BZDs when its dose descended to 0.5mg per day. Hamilton Anxiety Scale （HAMA-14） was used to assess the most serious anxiety level within withdrawal process. T test or chi square test were used to compare the differences of HAMA score, the incidence of withdrawal symptoms. Results： HAMA score of each group increased significantly within withdrawal process （P〈0.01）. The scores of HAMA, mental anxiety, fear, insomnia, and withdrawal symptoms incidence of clonazepam group were significantly higher than that of lorazepam group. Conclusion： Patients treated with BZDs for 4-6 weeks could present withdrawal symptoms. Withdrawal anxiety level of clonazepam group is higher than the lorazepam group. Insomnia, mental anxiety is more prominent. Shorter term use of BZDs, preferential selection of short acting and low affinity BZDs drugs, and on-demand use them may help to reduce withdrawal symptoms and dependence.