Rickels K, Freeman E W
Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia, USA.
J Clin Psychiatry. 2000 Jun;61(6):409-13. doi: 10.4088/jcp.v61n0603.
We examined discontinuation symptoms following brief benzodiazepine therapy (8 weeks) and intermittent benzodiazepine therapy (2 weeks with at least 2 weeks without drug) and associations with prior benzodiazepine use. The hypothesis was that prior benzodiazepine use would predispose patients to more severe discontinuation symptoms.
Data were drawn from 3 double-blind, randomized, placebo-controlled, published treatment trials: alprazolam for patients with premenstrual syndrome (PMS) and diazepam and lorazepam for patients with generalized anxiety disorder (GAD). The PMS group provided prospective daily symptom ratings, which allowed ongoing investigation of effects of prior treatment. In the GAD groups, taper outcome was examined after 8 weeks of benzodiazepine therapy as a function of prior benzodiazepine use and as a function of time since last prior benzodiazepine use. Symptom scores were analyzed using t statistics in the PMS group and analysis of covariance with 8-week scores as the covariate in the GAD groups.
The PMS subjects reported no increase in symptom scores and no significant difference from placebo-treated subjects during taper and discontinuation of alprazolam in the follicular phase of each treatment cycle. In the GAD trials, the results of treatment discontinuation did not differ significantly as a function of presence or absence of prior benzodiazepine use or as a function of time since last benzodiazepine use.
These preliminary data fail to support the hypothesis that prior benzodiazepine use predisposes patients to more severe discontinuation symptoms when treatment is brief and doses are low.
我们研究了短期苯二氮䓬类药物治疗(8周)和间歇性苯二氮䓬类药物治疗(2周用药,至少2周停药)后的戒断症状,以及与既往苯二氮䓬类药物使用情况的关联。假设是既往使用苯二氮䓬类药物会使患者出现更严重的戒断症状。
数据来自3项已发表的双盲、随机、安慰剂对照治疗试验:用于经前综合征(PMS)患者的阿普唑仑,以及用于广泛性焦虑症(GAD)患者的地西泮和劳拉西泮。PMS组提供前瞻性每日症状评分,以便持续研究既往治疗的效果。在GAD组中,在苯二氮䓬类药物治疗8周后,根据既往苯二氮䓬类药物使用情况以及距上次使用苯二氮䓬类药物的时间,检查撤药结果。PMS组使用t统计量分析症状评分,GAD组以8周评分作为协变量使用协方差分析。
PMS受试者在每个治疗周期的卵泡期停用阿普唑仑期间,报告症状评分未增加,与安慰剂治疗的受试者无显著差异。在GAD试验中,停药结果在有无既往苯二氮䓬类药物使用情况或距上次使用苯二氮䓬类药物的时间方面没有显著差异。
这些初步数据未能支持以下假设,即当治疗时间短且剂量低时,既往使用苯二氮䓬类药物会使患者出现更严重的戒断症状。