Relationship of Zolpidem and Cancer Risk: A Taiwanese Population-Based Cohort Study

Abstract

Objective: To evaluate the relationship between the use of zolpidem and subsequent cancer risk in Taiwanese patients. Methods: We used data from the National Health Insurance system of Taiwan to investigate whether use of zolpidem was related to cancer risk. For the study cohort, we identified 14,950 patients who had received a first prescription for zolpidem from January 1, 1998, through December 31, 2000. For each zolpidem user, we selected randomly 4 comparison patients without a history of using zolpidem who were frequency-matched by sex, age, and year of the index date. Incidence rates of all cancers and selected site-specific cancers were measured by the end of 2009, and related hazard ratios (HRs) and 95% confidence intervals (CIs) of the cancer were measured as well. Results: The risk of developing any cancer was greater in patients using zolpidem than in nonusers (HR, 1.68; 95% CI, 1.55-1.82). The stratified analysis showed that the overall HR for high-dosage zolpidem (Ն300 mg/y) was 2.38. The site-specific cancer risk was the highest for oral cancer (HR, 2.36; 95% CI, 1.57-3.56), followed by kidney cancer, esophageal cancer, breast cancer, liver cancer, lung cancer, and bladder cancer (HR, 1.60; 95% CI, 1.06-2.41). Men were at higher risk than women. Conclusion: This population-based study revealed some unexpected findings, suggesting that the use of zolpidem may be associated with an increased risk of subsequent cancer. Further large-scale and in-depth investigations in this area are warranted.

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

“…(2) Consistency is the strongest evidence, with 33 of 34 studies showing a positive association of hypnotic consumption and mortality. (3) Several kinds of specificity of hypnotics-mortality associations have been identified: the excess of deaths at night among hypnotics users [21], the excesses of infection [13], COPD [57], and suicide deaths [50], and the excess of specific cancers such as lung and esophagus [38]. (4) The temporality of hypnotic usage preceding death is consistent with causation.…”

“…Moreover, hypnotics are epidemiologically associated with an increased rate of driver-at-fault vehicle crashes as well as falls and serious infections [13,[27][28][29][30][31][32][33][34][35][36]. Other studies show that hypnotic use is associated with new cancer incidence [37][38][39]. Such studies fall somewhat short of causal proof that hypnotics cause deaths from injuries, infections, suicide, and cancer, but for purposes of epidemiologic studies, it should be assumed that hypnotic prescribing may produce reverse causation of several forms of comorbidity, as suggested in Fig.…”

Reply to ‘Evidence for harm, comment on …’ by Kripke & Langer

“…As highlighted by Kripke & Langer [1], subsequent studies by Kao et al [7,8] have replicated their findings of an increased cancer risk associated with use of BZRD. However, the selection procedure applied in these studies seems to suffer from the same flaw as explained above [7,8].…”

Insomnia, Hypnotic Drug Use, and Patient Well-being: First, Do No Harm

“…The 2 report that the risk of developing cancer was greater for individuals who were prescribed the most popular nonbenzodiazepine hypnotic, zolpidem, than for those who were not. There was also a small but statistically significant increase in cancer risk for those who took benzodiazepine hypnotics.…”

“…They are more likely to smoke, to be obese, and to have chronic medical or psychiatric conditions. [2][3][4][5][6][7][8] Although the reports by both Kao et al 2 and Kripke et al 5 controlled for many confounders, it is likely that lifestyle factors and comorbities of those with insomnia contribute to at least part of the increased risk. For that reason, we must keep in mind that association doesn't prove causality.…”