Global burden of insomnia medication-associated suicidality, 1967-2024: A disproportionality analysis of the global pharmacovigilance database.

BACKGROUND

While insomnia is recognized as a risk factor for suicidality, the potential influence of insomnia medications on this risk requires further investigation.

METHODS

We utilized the global pharmacovigilance database, to detect pharmacovigilance signal of insomnia medication-related suicidality from 1967 to 2024. The analysis included benzodiazepines, Z-drugs, antidepressants, first-generation H1 antagonists, and dual orexin receptor antagonists for insomnia medications. Multivariable logistic regression models were used to calculate the reporting odds ratio (ROR) and 95 % confidence interval (CI) of suicidality for each medication class, adjusting for age, sex, and reporting region, with melatonin and its receptor agonist as the reference.

RESULTS

We identified 13,899 reports of suicidality associated with insomnia medications. Benzodiazepines (ROR, 1.78 [95 % CI, 1.62-1.97]), Z-drugs (1.52 [1.40-1.66]), antidepressants (2.08 [1.88-2.31]), and first-generation H1 antagonists (1.59 [1.45-1.73]) showed stronger signal of suicidality compared to melatonin and its receptor agonist. In contrast, dual orexin receptor antagonists (ROR, 0.36 [0.31-0.42]) exhibited a lower signal risk. The melatonin receptor agonist ramelteon (ROR, 0.29 [0.21-0.39]) showed a weaker signal than melatonin. Similarly, dual orexin receptor antagonists suvorexant (ROR, 0.31 [0.26-0.37]), daridorexant (0.20 [0.14-0.29]), and lemborexant (0.24 [0.11-0.51]) significantly lowered the signal risk of suicidality compared to melatonin.

CONCLUSIONS

Although this disproportionality analysis did not permit causal interpretation, our study highlights significant variations in suicidality signal risk among insomnia medications, with benzodiazepines, Z-drugs, antidepressants, and first-generation H1 antagonists posing stronger signal, and dual orexin receptor antagonists presenting a weaker signal. Given the limitations of pharmacovigilance data, further studies are needed to confirm these findings and guide safer prescribing practices, particularly for individuals at high risk of suicidality.