<p>Widespread use of prescription opioids has been a major public health concern since 1999. Many consequences are associated with the problem, such as opioid misuse, abuse, and drug overdose deaths. Opioids are not the only medications involved with drug overdose deaths. Due to stricter control of prescription opioids, those who misused opioids are associated with initiation of another illicit drug abuse. This results in increased drug overdose death involving heroin and semisynthetic/synthetic opioids. Another risk factor for increased overdose death is concurrent use of opioids with other central nervous system (CNS) depressants and some anticonvulsants. Concurrent use of opioids and benzodiazepine, z-drugs (zolpidem and zaleplon), gabapentin, and/or pregabalin is associated with increased risk of respiratory depression and drug overdose death. To combat problematic opioid use, many mitigation strategies were introduced. However, opioid-related problems remain.</p>