Bethge K P, Godt U, Blanco-Cruz E, Lichtlen P R
J Cardiovasc Pharmacol. 1982 Jan-Feb;4(1):142-8. doi: 10.1097/00005344-198201000-00023.
In a prospective randomized study we searched for arrhythmogenic effects of the tetracyclic antidepressant, a maprotiline, and the tetrahydroisoquinoline derivative, nomifensine. Forty depressive patients from the psychiatric outpatients department were included in the study. Twenty patients in each group received maprotiline or nomifensine over three weeks in the recommended daily dosage of 75 mg. Rhythm analysis was performed before therapy, at the end of 3 weeks therapy, and 1 week after withdrawal from medication using a dual channel long-term ECG with monitoring periods of 10 h during normal daily activities. Before treatment, spontaneous incidence of all ventricular ectopics and of their complex forms was within the normal range when compared with ectopic activity of 121 "normal subjects" without detectable heart disease. No significant increase could be demonstrated during therapy with maprotiline or nomifensine, nor was any change observed 1 week after medication had been stopped. The same was true for supraventricular extrasystoles; atrial tachycardia, atrial flutter, and fibrillation were never seen. Sinoatrial (n=2) and atrioventricular block (n=1) were rare findings independent of and not affected by treatment. No bundle branch blocks were observed before, during, and after treatment. In contrast, despite the conservative dosage of both drugs, a therapy-dependent increase in average heart rate was found (p less than 0.001). This increase was significantly higher in patients receiving nomifensine than in those treated with maprotiline (p less than 0.001), suggesting a lower intrinsic anticholinergic activity of the latter compound.
在一项前瞻性随机研究中,我们探究了四环类抗抑郁药麦普替林和四氢异喹啉衍生物诺米芬辛的致心律失常作用。该研究纳入了40名来自精神科门诊的抑郁症患者。每组20名患者,连续三周按照推荐日剂量75毫克服用麦普替林或诺米芬辛。在治疗前、治疗3周结束时以及停药1周后,使用双通道长期心电图进行节律分析,监测正常日常活动期间10小时的心电情况。治疗前,与121名无明显心脏病的“正常受试者”的异位活动相比,所有室性早搏及其复合形式的自发发生率均在正常范围内。在服用麦普替林或诺米芬辛治疗期间,未发现明显增加,停药1周后也未观察到任何变化。室上性早搏情况相同;从未见过房性心动过速、心房扑动和心房颤动。窦房阻滞(n = 2)和房室阻滞(n = 1)为罕见发现,与治疗无关且不受治疗影响。治疗前、治疗期间及治疗后均未观察到束支阻滞。相比之下,尽管两种药物剂量保守,但仍发现治疗依赖性平均心率增加(p < 0.001)。接受诺米芬辛治疗的患者心率增加明显高于接受麦普替林治疗的患者(p < 0.001),这表明后者化合物的内在抗胆碱能活性较低。