Hantouche E G, Guelfi J D, Comet D
Département de Psychiatrie, Groupe Hospitalier de la Pitié-Salpêtrière, Paris.
Encephale. 1998 Sep-Oct;24(5):469-79.
To evaluate the efficacy of alpha-beta L-Aspartate Magnesium (Asp Mg) in discontinuation of long-term benzodiazepine use and to search for a predictive model of success for BZD cessation.
Using a double-blind procedure, 144 patients selected as chronic users of one of 3 BZD lorazepam, alprazolam or bromazepam (duration of use > 6 months; regular dose > or = 3 mg lorazepam equivalent) and with clinical remission (score on Hamilton-Anxiety < 14; Raskin-Depression < 6) had entered a controlled study (versus placebo) and were randomized in two parallel groups. The trial was conducted on 3 consecutive phases (co-administration of Asp Mg or placebo with BZD during 1 month; gradual taper of BZD during 1 month; follow-up during a third month after complete BZD discontinuation, with urinary BZD control on d75 and d90).
The intent-to-treat analysis showed at the endpoint an overall rate of 80% of "BZD discontinuation" and of 35.4% of "BZD cessation without withdrawal" in the total population (no significant intergroup differences were observed on these rates). However, there were some tendencies to positive differences between Asp Mg versus placebo on the following: 1) prolonged delay of BZD use if reintake (30 days vs 20 days, p [log-rank] = 0.5); 2) reduction of withdrawal intensity: 11% of important difficulties during BZD cessation versus 23% with placebo (p = 0.2) and on Benzodiazepine Withdrawal Symptoms Questionnaire (BWSQ) (final score 4.0 vs 4.8, p = 0.10); 3) lower modification of anxiety during BZD tapering and discontinuation (rate of increase on HAM-A between d30-d90 of 6% vs 23% in placebo group, p = 0.10). Moreover, 3 predictive factors of "success" (BZD cessation without withdrawal phenomenon) were identified by uni- and multivariate analysis with logistic regression: chronicity of anxiety disorder (p = 0.04) and amplitude of BWSQ change during tapering phase (p < 0.0001) as negative factors; and initial score of Speilberger Anxiety Inventory "Anxiety-Trait" (p = 0.002) as positive factor. A predictive model is constructed according to these 3 parameters. Further clinical trials are needed to explore the benefits of alpha-beta L-Aspartate Magnesium in different criteria of prescription (dosage, duration of treatment, repetitive cures...).
评估α-β 天门冬氨酸镁（Asp Mg）在停用长期苯二氮䓬类药物方面的疗效，并寻找苯二氮䓬类药物戒断成功的预测模型。
采用双盲程序，144名被选为三种苯二氮䓬类药物（劳拉西泮、阿普唑仑或溴西泮）之一的长期使用者（使用时间>6个月；常规剂量>或 = 3mg劳拉西泮等效剂量）且临床症状缓解（汉密尔顿焦虑量表评分<14；拉斯金抑郁量表评分<6）的患者进入一项对照研究（与安慰剂对照），并随机分为两个平行组。试验分三个连续阶段进行（Asp Mg或安慰剂与苯二氮䓬类药物联合使用1个月；苯二氮䓬类药物逐渐减量1个月；在完全停用苯二氮䓬类药物后的第三个月进行随访，在第75天和第90天检测尿中苯二氮䓬类药物）。
意向性分析显示，在终点时，总体人群中“停用苯二氮䓬类药物”的比例为80%，“无戒断反应停用苯二氮䓬类药物”的比例为35.4%（在这些比例上未观察到组间显著差异）。然而，Asp Mg与安慰剂相比在以下方面存在一些积极差异的趋势：1）如果重新使用苯二氮䓬类药物，使用延迟延长（30天对20天，p[对数秩检验]=0.5）；2）戒断强度降低：苯二氮䓬类药物戒断期间出现严重困难的比例为11%，而安慰剂组为23%（p = 0.2），以及在苯二氮䓬类药物戒断症状问卷（BWSQ）上（最终得分4.0对4.8，p = 0.10）；3）在苯二氮䓬类药物减量和停药期间焦虑的变化较小（第30天至第90天汉密尔顿焦虑量表增加率为6%，而安慰剂组为23%，p = 0.10）。此外，通过单因素和多因素逻辑回归分析确定了“成功”（无戒断现象停用苯二氮䓬类药物）的3个预测因素：焦虑症的慢性程度（p = 0.04）和减量阶段BWSQ变化幅度（p < 0.0001）为负因素；以及斯皮尔伯格焦虑量表“焦虑特质”初始得分（p = 0.002）为正因素。根据这3个参数构建了一个预测模型。需要进一步的临床试验来探索α-β 天门冬氨酸镁在不同处方标准（剂量、治疗持续时间、重复治疗……）下的益处。
