Concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem and risk for suicide: a case-control and case-crossover study.

PURPOSE: To evaluate whether the concurrent use of benzodiazepines, antidepressants, and opioid analgesics with zolpidem increases the risk of suicide or triggers suicide compared with the use of zolpidem alone. METHODS: We conducted a case-control and case-crossover study using the Korean National Health Insurance Service-National Sample Cohort database. Cases were older than 20 years with a suicide record (International Codes of Disease 10th Revision codes: X-60-X84 and Y87.0 intentional self-harm) between January 1, 2004, and December 31, 2013. For case-control design, ten controls were matched to each case by age, sex, index year, region, income, and health insurance type. For case-crossover analysis, we set hazard period to 60 days and assigned five corresponding sets of control periods of equal length. Exposure was assessed during 60 days before suicide for combinations of benzodiazepines, antidepressants, opioid analgesics with zolpidem against zolpidem alone. We conducted a conditional logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: In the case-control study, the risk of suicide was 2.80-fold higher in cases taking benzodiazepines and antidepressants with zolpidem than in those taking zolpidem alone (adjusted OR [aOR], 2.80; 95% CI, 1.38-5.70). However, in the case-crossover study, suicide risk showed no significant difference (crude OR [cOR], 0.92; 95% CI, 0.55-1.52) and was underpowered. CONCLUSIONS: The results of the traditional case-control study confirmed that the concurrent use of benzodiazepines and antidepressants with zolpidem was associated with an increased risk of suicide compared with the use of zolpidem alone. However, there was no significant difference in the magnitude of risk in the within-person comparison design.

Zolpidem Use and Suicide Death in South Korea: A Population-Based Case-Control Study.

OBJECTIVE: To investigate whether zolpidem use is associated with suicide death in adults. METHOD: We conducted a case-control study using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Cases were adults with a suicide record (ICD-10 codes; X-60-X84, Y87.0) between January 1, 2004 and December 31, 2013. 10 Controls were matched to each case by age, sex, index year, region, income level, and health insurance type. Zolpidem use during 2 years before suicide was quantified. Adjusted odd ratios (aORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. RESULTS: The percentage of zolpidem users was significantly higher in cases (451 of 1,928 [23.4%]) than in controls (832 of 18,404 [4.5%]). After controlling for potential confounders, zolpidem use was significantly associated with suicide (aORs, 2.09; 95% CI, 1.74-2.52). Dose-response relationships were observed (for trend, p < .0001). Consistent findings were observed when analyses were restricted to suicide death (aORs, 2.08; 95% CI, 1.73-2.51) and nonmedication poisoning suicide death cases (aORs, 2.10; 95% CI, 1.74-2.53). CONCLUSIONS: We found a significant and positive association between zolpidem use and suicide. Zolpidem should be prescribed cautiously and with due caution of increased suicide risk.

Signal detection of benzodiazepine use and risk of dementia: sequence symmetry analysis using South Korean national healthcare database.

Background Benzodiazepine use can potentially cause confusion and delays in mental processes. These well-known side effects appear to be linked to an increased risk of being diagnosed with dementia. Objective To evaluate the possibility of an association between benzodiazepine and dementia. Setting Korean healthcare database from 2002 to 2013. Methods Sequence symmetry analysis was conducted to investigate whether benzodiazepine use increases the risk of dementia or not. We defined exposure as new benzodiazepine users and outcome as new diagnosis of dementia (ICD-10: F00-03, G30, and G318). Benzodiazepines were categorized into two groups (long-acting and short-acting) based on the duration of action. Antidepressants, opioid analgesic, and statin were used as active comparators to rule out any possible non-causal interpretations of our results. The time-trend adjusted sequence ratio (ASR) with 95% confidence intervals (CI) was measured to identify possible associations. Main outcome measure Adjusted sequence ratio. Results Benzodiazepine users were shown to be associated with dementia [benzodiazepine: 4212 pairs, ASR = 2.27 (95% CI 2.11-2.44)]. In addition, long-acting benzodiazepines had a higher ASR than that of short-acting benzodiazepines [long-acting: 3972 pairs, ASR = 2.22 (95% CI 2.06-2.39] and [short-acting: 5213 pairs, ASR = 1.88 (95% CI 1.77-2.00)]. However, our SSA found no duration-response relationship. Conclusion Our signal detection suggests that there is a possible association between benzodiazepines and dementia. Additionally, it proposes that persons receiving long-acting benzodiazepines are at a higher risk of developing dementia than those receiving short-acting benzodiazepines. Further studies are recommended to confirm whether this epidemiological association is a causal effect or not.