Zopiclone-associated hallucinations: a case report and database pharmacovigilance study.

Aims: Zopiclone is widely prescribed for insomnia, but the pharmacovigilance reporting signals for hallucinations remain poorly characterized. This study combines a case report and pharmacovigilance data to evaluate the association between zopiclone and hallucinations, compare hallucination subtype signals, and examine factors associated with higher reporting odds. Methods: We reported a clinical case assessed by the Naranjo scale and analyzed the Canadian Vigilance Adverse Reaction Database (1994-2025) for zopiclone-associated hallucinations. Three disproportionality methods (ROR, PRR, and BCPNN-IC) were used for signal detection. Univariate and multivariate logistic regression were applied to identify factors associated with higher reporting odds. Results: In the presented case, auditory hallucinations worsened following zopiclone initiation and improved after discontinuation, with a Naranjo score of 4, suggesting a possible temporal association. A total of 58 valid cases of zopiclone-associated hallucinations were included in the database, accounting for 2.41% of all zopiclone-associated adverse events. All three algorithms detected positive disproportionality signals for zopiclone-associated hallucinations, with auditory hallucinations showing a numerically higher point estimate (ROR = 4.71, 95% CI: 2.87-7.72), visual hallucinations (ROR = 3.49, 95% CI: 2.13-5.72), and hallucination (ROR = 2.39, 95% CI: 1.70-3.37). Multivariate logistic regression analysis showed that age ≥ 65 years was independently associated with higher reporting odds of zopiclone-associated hallucinations (adjusted OR = 2.48, 95% CI: 1.42-4.30, P < 0.01). Sex was not independently associated with reporting odds of hallucinations, while BMI was not included in the multivariable model because of substantial missing data. Conclusion: Zopiclone is associated with a reporting signal for hallucinations, with auditory hallucinations showing a numerically higher point estimate in this dataset. Age ≥ 65 years was independently associated with approximately 2.5-fold higher reporting odds of zopiclone-associated hallucinations. Caution is warranted when prescribing zopiclone to elderly patients. These findings represent pharmacovigilance signals derived from spontaneous adverse-event reports and do not imply causality. The database contained only one schizophrenia case (n = 1); therefore, no subgroup-specific conclusion can be drawn.