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

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.

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.

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.

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.