University of Hertfordshire

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Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Journal publication date5 Feb 2019
Early online date5 Feb 2019
Publication statusE-pub ahead of print - 5 Feb 2019


Background: Although originally marketed as safe alternatives to the habit-forming benzodiazepines, growing numbers of zaleplon, zolpidem, and zopiclone (‘Z-drugs’) clinical concerns relating to their potential of abuse, dependence and withdrawal have been reported overtime. We aimed here at assessing these issues analysing datasets of Adverse Drug Reactions (ADR) provided by the European Medicines Agency (EMA) through the EudraVigilance (EV) system.
Methods: Analysing the ADR databases of each Z-drug, a descriptive analysis have been performed on cases, and Proportional Reporting Ratios (PRRs) computed.
Results: An overall number of 33,240 (e.g. 23,240 zolpidem; 9,283 zopiclone; and 537 zaleplon) misuse/abuse/dependence/withdrawal-related ADRs, corresponding to some 6,246 unique patients given Z-drugs, were here identified. Cases were studied and described, including demographic characteristics and clinical data, such as concomitant drugs, doses, routes of administration, and outcomes of the reactions, being fatalities recorded. Considering PRR values, and in comparison with zopiclone, zolpidem was more frequently involved in both misuse/abuse and withdrawal issues. Zolpidem and zopiclone presented with the same dependence risk, but zopiclone was the most involved in overdose ADRs. If compared with zaleplon, zopiclone presented higher dependence and overdose -related issues, but slightly lower misuse/abuse and withdrawal PRR values.
Conclusion: Current data may only represent a gross underestimate of the Z-drugs’ misusing issues’ real prevalence. Caution should be exercised when prescribing those molecules, especially for patients with psychiatric illnesses and/or history of drug abuse. We recommend the need to invest in proactive pharmacovigilance activities to better and promptly detect, understand and prevent any possible misusing potential of prescribed medications.


© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.

ID: 16216167