Busto U E, Naranjo C A, Bremner K E, Peachey J E, Bologa M
University of Toronto, Sunnybrook Health Science Centre, Psychopharmacology Research Program, North York, ON.
J Psychiatry Neurosci. 1998 Jan;23(1):35-44.
To determine discontinuation effects of ipsapirone, a novel azapirone and partial 5-HTIA agonist that has anxiolytic effects clinically and has not caused dependence or withdrawal symptoms in animals, and to compare these effects with those of the benzodiazepine lorazepam, owing to concern about dependence or withdrawal symptoms following use of these drugs.
Prospective, randomized, double-blind, placebo-controlled trial.
Outpatient and inpatient treatment.
Sixty-five healthy male volunteers who had experience with sedative-hypnotics or anxiolytics and did not meet DSM-III-R criteria for abuse or dependence.
Participants were randomized to receive ipsapirone 15 mg per day (n = 17), ipsapirone 22.5 mg per day (n = 16), lorazepam 3 mg per day (n = 16), or placebo (n = 16) as outpatients for 36 days (treatment) followed by single-blind placebo as inpatients for 3 days and as outpatients for 6 days (withdrawal).
Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale (HAM-D), Spielberger State Anxiety Scale, Sleep Quality Questionnaire, General Symptom Checklist, self-rated intoxication, Clinical Institute Withdrawal Assessment--Benzodiazepines (CIWA-Benzo), psychomotor testing and urine drug screen.
Only 45 subjects completed the study; discontinuation rates did not significantly differ among treatment groups. At day 39, fewer and less severe symptoms (e.g., insomnia and fatigue) were found on the CIWA-Benzo scale after treatment with ipsapirone or placebo than after treatment with lorazepam (p < 0.05). Subjects reported longer sleep latency and poorer sleep quality after receiving lorazepam than after receiving ipsapirone or placebo. Scores on the HAM-D, Spielberger State Anxiety and HAM-A scales did not change from baseline.
Withdrawal symptoms were detected after discontinuation of therapeutic doses of lorazepam. Significantly fewer symptoms were observed after withdrawal from anxiolytic doses of ipsapirone.
确定伊沙匹隆（一种新型氮杂螺环酮及部分5-羟色胺1A受体激动剂，临床上具有抗焦虑作用且在动物实验中未引起依赖或戒断症状）的撤药效应，并将这些效应与苯二氮䓬类药物劳拉西泮的效应进行比较，因为人们担心使用这些药物后会出现依赖或戒断症状。
前瞻性、随机、双盲、安慰剂对照试验。
门诊及住院治疗。
65名有使用镇静催眠药或抗焦虑药经历且不符合DSM-III-R滥用或依赖标准的健康男性志愿者。
参与者被随机分为门诊接受每日15毫克伊沙匹隆（n = 17）、每日22.5毫克伊沙匹隆（n = 16）、每日3毫克劳拉西泮（n = 16）或安慰剂（n = 16）治疗36天（治疗期），之后住院单盲接受安慰剂治疗3天，门诊再接受安慰剂治疗6天（撤药期）。
汉密尔顿焦虑量表（HAM-A）、汉密尔顿抑郁量表（HAM-D）、斯皮尔伯格状态焦虑量表、睡眠质量问卷、一般症状清单、自我评定的中毒情况、临床研究所苯二氮䓬类药物撤药评估（CIWA - 苯二氮䓬）、精神运动测试及尿液药物筛查。
仅45名受试者完成了研究；各治疗组的撤药率无显著差异。在第39天，与劳拉西泮治疗后相比，伊沙匹隆或安慰剂治疗后在CIWA - 苯二氮䓬量表上出现的症状更少且症状较轻（例如失眠和疲劳）（p < 0.05）。与接受伊沙匹隆或安慰剂后相比，接受劳拉西泮后受试者报告的睡眠潜伏期更长且睡眠质量更差。HAM-D、斯皮尔伯格状态焦虑量表及HAM-A量表的得分与基线相比未发生变化。
停用治疗剂量的劳拉西泮后检测到了撤药症状。从抗焦虑剂量的伊沙匹隆撤药后观察到的症状明显较少。
