Tariot P N, Jakimovich L J, Erb R, Cox C, Lanning B, Irvine C, Podgorski C A
Department of Psychiatry, University of Rochester Medical Center, and the Program in Neurobehavioral Therapeutics, Monroe Community Hospital, NY 14620, USA.
J Clin Psychiatry. 1999 Oct;60(10):684-9. doi: 10.4088/jcp.v60n1007.
The aim of this study was to assess the effects of withdrawal from placebo and carbamazepine administered for agitation associated with dementia and to assess safety, tolerability, and efficacy of subsequent ongoing carbamazepine therapy.
We previously reported the results of a 6-week, randomized, parallel-group study of placebo versus carbamazepine in 51 nursing home patients with dementia who were agitated; 47 subjects completed that study. This report first presents the results of withdrawal from that experimental treatment assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary outcome measures addressed other aspects of behavior, cognition, function, safety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), with the same assessments performed.
Patients who had previously shown behavioral improvement with carbamazepine therapy reverted to their baseline state after washout, whereas there was no change in the patients previously treated with placebo. There were no other significant effects of washout. During subsequent therapy with carbamazepine at a modal dose of 300 mg/day, there were 2 deaths and 4 other adverse events resulting in dropout. Neither of the deaths, and only 1 serious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavior ratings showed ongoing improvement in agitation and aggression, as well as in other aspects of psychopathology.
The washout data provided independent confirmation of efficacy found in the prior placebo-controlled phase of this trial. Ongoing treatment was not associated with unexpected toxicity and was associated with improvement in measures of agitation and aggression that appeared to continue for up to 12 weeks. These findings confirm and extend results from earlier placebo-controlled studies.
本研究旨在评估停用用于治疗与痴呆相关激越的安慰剂和卡马西平的效果，并评估后续持续使用卡马西平治疗的安全性、耐受性和疗效。
我们之前报告了一项为期6周的随机平行组研究结果，该研究对比了安慰剂与卡马西平对51名患有激越症状的痴呆养老院患者的疗效；47名受试者完成了该研究。本报告首先呈现了3周后通过（盲法）观察评估的该实验性治疗撤药结果（剩余45名）。主要结局指标为简明精神病评定量表。次要结局指标涉及行为、认知、功能、安全性和耐受性的其他方面。然后患者接受额外6周（剩余32名）或12周（剩余25名）的卡马西平治疗，并进行相同评估。
先前接受卡马西平治疗且行为改善的患者在洗脱期后恢复至基线状态，而先前接受安慰剂治疗的患者无变化。洗脱期无其他显著影响。在随后以300毫克/天的典型剂量使用卡马西平治疗期间，有2例死亡和4例其他不良事件导致退出研究。2例死亡均与卡马西平无关，只有1例严重不良事件被判定与卡马西平有关。试验期间有多种非严重不良事件。行为评分显示激越和攻击行为以及精神病理学的其他方面持续改善。
洗脱期数据独立证实了本试验先前安慰剂对照阶段发现的疗效。持续治疗未出现意外毒性，且与激越和攻击行为指标的改善相关，这种改善似乎持续长达12周。这些发现证实并扩展了早期安慰剂对照研究的结果。
