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. 2019 May 21;10(10):2288-2298.
doi: 10.7150/jca.30680. eCollection 2019.

Association between Sedative-hypnotics and Subsequent Cancer in Patients with and without Insomnia: A 14-year Follow-up Study in Taiwan

Hui-Fen Fang  1 , Tzu-Yin Lee  2 , King Cheung Hui  2 , Howard Chi Ho Yim  3 , Mei-Ju Chi  4 , Min-Huey Chung  2   5
Affiliations

Association between Sedative-hypnotics and Subsequent Cancer in Patients with and without Insomnia: A 14-year Follow-up Study in Taiwan

Hui-Fen Fang et al. J Cancer. .

Abstract

Background: The aim of this population-based 14-year historical and prospective study was to determine the relationships between the usage of sedative-hypnotics, including benzodiazepines and nonbenzodiazepines, and the risk of subsequent cancer in patients with or without insomnia among the Taiwanese population. Methods: A total of 43,585 patients were recruited, 21,330 of whom had been diagnosed with insomnia and 8,717 who had been prescribed sedative-hypnotics during this study's following period of 2002 to 2015. Information from the claims data, namely basic demographic details, drug prescriptions, comorbidities, and patients' survival, was extracted from the National Health Insurance Research Database for χ2 analysis. A Cox proportional hazards model was used to compute the 14-year cancer-free survival rates after adjustment for confounding factors. Results: Patients with insomnia who used sedative-hypnotics had an adjusted hazard ratio of 1.49 compared with patients with insomnia who did not use any sedative-hypnotics, and patients without insomnia who used sedative-hypnotics had an adjusted hazard ratio of 1.68 compared with patients without insomnia who did not use any sedative-hypnotics. Regarding site-specific risk, patients with insomnia who used sedative-hypnotics had an increased risk of oral and breast cancers, and patients without insomnia who received sedative-hypnotics prescriptions had an increased risk of liver and breast cancers. The cancer-free survival rate of patients who had used sedative-hypnotics was significantly lower than that of patients who had never used sedative-hypnotics. Conclusions: The use of sedative-hypnotics in patients either with or without insomnia was associated with subsequent cancer development in the Taiwanese population. Increased risks of oral, liver, and breast cancer were found in the patients with the use of sedative-hypnotics. The use of sedative-hypnotics should be discouraged for treating patients with or without insomnia in Taiwan.

Keywords: Cancer; Cancer-free survival rate; Immune function; Insomnia; Sedative-hypnotics; Viral infection.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Cancer-free survival rates of patients in Inso-Hyp, Inso-NonHyp, NonInso-Hyp, and NonInso-NonHyp groups. Inso-Hyp, patients with insomnia and sedative-hypnotic prescriptions; Inso-NonHyp, patients with insomnia and without sedative-hypnotic prescriptions; NonInso-Hyp, patients with sedative-hypnotics and without insomnia; NonInso-NonHyp, patients with neither insomnia nor sedative-hypnotic prescriptions
Figure 2
Figure 2
A diagram showing a potential mechanism how BZDs, such as diazepam or midazolam, contribute to the increased risk of subsequent cancers, such as oral and liver cancers, in this study. The numbers refer to the corresponding supporting references.
Figure 3
Figure 3
A diagram showing the relationships between psychological illnesses, sedative-hypnotics and impaired immune function.
Figure 4
Figure 4
A diagram showing a potential mechanism how non-BZDs such as zopiclone or zaleplon contribute to increased risk of subsequent cancers. The number refers to the corresponding supporting reference.
See this image and copyright information in PMC

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