The DOI matches its Crossref record; 72 of the 74 references it cites were found in a registry or an index.
Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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In the citing paper
“Evidence 9 28 suggests that zopiclone carries a potential for dependence.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [28]
In the citing paper
“This elevated risk among older adults is partly attributed to the higher prevalence of sleep and mood disorders in this population, as well as to age-related reductions in drug clearance.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [28]
In the citing paper
“Studies 28 have shown that a history of psychiatric illness, as well as concurrent use of alcohol or other substances, significantly increases the risk of Z-drug misuse.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [28]
In the citing paper
“Psychiatric comorbidities are common among individuals with Z-drug use disorder, particularly depressive, anxiety, and personality disorders.”
From Z-drug abuse and dependence: Clinical guideline of the Brazilian Academy of Neurology for diagnosis and management (2025) · cites this paper as [28]
In the citing paper
“In addition to their therapeutic potential, these medications also have reinforcing properties (1–3) and thus can be misused”
From Prevalence and correlates of the misuse of z-drugs and benzodiazepines in the National Survey on Drug Use and Health (2023) · cites this paper as [1]
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Background
Metadata
- Authors
- Hajak, G., Müller, W. E., Wittchen, H. U., Pittrow, D., & Kirch, W.
- Affiliations
- University of Regensburg (DE)
- Goethe University Frankfurt (DE)
- Technische Universität Dresden (DE)
- Corresponding author
- Hajak, G.
- Venue
- Addiction
- Publisher
- Wiley
- Published
- 2003-10
- Volume
- 98
- Issue
- 10
- Pages
- 1371-1378
- ISSN
- 0965-2140 (ISSN-L)
- 1360-0443
- OpenAlex
- W2116289594
- Cited by
- 404
- References
- 74
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 19 · 2022: 11 · 2021: 16 · 2020: 29 · 2019: 21 · 2018: 17 · 2017: 13 · 2016: 25 · 2015: 13 · 2014: 27 · 2013: 19 · 2012: 20
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Addiction (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- zolpidem, zopiclone, non-benzodiazepine hypnotics, drug addiction, drug abuse, insomnia treatment, benzodiazepine alternatives, prescribing patterns, psychiatric comorbidity, withdrawal, drug safety
- MeSH terms
- Zolpidem, Adult, Aged, Female, Humans, Hypnotics and Sedatives, Male, Middle Aged, Piperazines, Pyridines, Substance-Related Disorders, Azabicyclo Compounds
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