Hajak G, Müller W E, Wittchen H U, Pittrow D, Kirch W
Department of Psychiatry and Psychotherapy, University of Regensburg, Germany.
Addiction. 2003 Oct;98(10):1371-8. doi: 10.1046/j.1360-0443.2003.00491.x.
The non-benzodiazepine hypnotics zolpidem and zopiclone, which are indicated for short-term treatment of insomnia, were considered originally by physicians as almost devoid of abuse and dependence potential. Several recent publications, however, have suggested that both agents carry a significant risk of abuse. To substantiate and re-evaluate this situation, the world literature was reviewed for cases of dependence of both agents; these cases were analysed in order to identify certain underlying patterns, if evident.
A systematic review based on a Medline literature search was conducted including the years 1966-2002 to assemble all available clinical case reports that were analysed for typical features of abuse and dependence according to prespecified criteria. Only case reports were of interest, and clinical studies were excluded. No limitations as to language or publication year were applied. The terms 'zolpidem', 'zopiclone' and 'abuse', 'dependence', 'addiction', 'withdrawal' and 'intoxication' were used to identify relevant publications. Potentially relevant citations were retrieved and assessed for inclusion independently by two authors.
A total of 36 cases for zolpidem were identified, most of them reported in recent years, and 22 cases for zopiclone. Both sexes were involved to a similar extent; and cases were reported in all age groups. In extreme cases, dose increases reached a factor of 30-120 above the recommended doses. The majority of patients had a history of former drug or alcohol abuse and/or other psychiatric conditions.
On the basis of world-wide prescription numbers, which are approximately twofold higher for zolpidem (1,338,774,000 tablets from June 2001 to June 2002 in Europe, Japan and United States) than for zopiclone (664,897,000 tablets during the same period in Europe and Japan), the relative incidence of reported dependence similar for both drugs and remarkably lower than that of benzodiazepines used for the treatment of disturbed sleep. The findings offer the conclusion that zolpidem and zopiclone are relatively safe drugs. However, as both drugs are psychotropic drugs, patients with a history of abuse or dependence and those with psychiatric diseases seem to be at increased risk of abuse of these agents.
非苯二氮䓬类催眠药唑吡坦和佐匹克隆用于失眠的短期治疗，最初医生认为它们几乎没有滥用和成瘾的可能性。然而，最近的一些出版物表明这两种药物都有显著的滥用风险。为了证实并重新评估这种情况，我们查阅了世界文献中关于这两种药物成瘾的病例；对这些病例进行分析，以确定是否存在某些潜在模式（如果有的话）。
基于对1966年至2002年期间的Medline文献检索进行系统综述，收集所有可用的临床病例报告，并根据预先设定的标准对其滥用和成瘾的典型特征进行分析。只纳入病例报告，排除临床研究。对语言和出版年份没有限制。使用“唑吡坦”、“佐匹克隆”以及“滥用”、“成瘾”、“上瘾”、“戒断”和“中毒”等术语来识别相关出版物。两位作者独立检索并评估潜在相关的文献以确定是否纳入。
共确定了36例唑吡坦成瘾病例，其中大多数是近年来报告的，还有22例佐匹克隆成瘾病例。男女比例相似；各年龄组均有病例报告。在极端情况下，剂量增加达到推荐剂量的30至120倍。大多数患者有既往药物或酒精滥用史和/或其他精神疾病史。
根据全球处方量，唑吡坦（2001年6月至2002年6月在欧洲、日本和美国的处方量为13.38774亿片）大约是佐匹克隆（同期在欧洲和日本的处方量为6.64897亿片）的两倍，两种药物报告成瘾的相对发生率相似，且明显低于用于治疗睡眠障碍的苯二氮䓬类药物。研究结果表明唑吡坦和佐匹克隆是相对安全的药物。然而，由于这两种药物都是精神药物，有滥用或成瘾史的患者以及患有精神疾病的患者似乎滥用这些药物的风险更高。
