br Methods br Results br Discussion This

Methods
Results
Discussion This study investigated which drug categories were responsible for the growth in fatal overdoses between 1999 and 2014 or sub-periods. Three challenges were encountered when attempting to answer this seemingly simple question. First, current death certificate data are problematic for understanding the drug poisoning epidemic, with a particular issue being the frequency that no specific drug was identified (Slavova et al., 2015). Second, combinations of drugs were often involved. This makes it difficult to assign responsibility to individual drug categories, or possibly meaningless to do so if the effects were interactive. It also implies that the contributions of drug categories, based on “any mentions”, will sum to more than 100% of the total number or change over time in drug deaths. Third, the contributions of different drugs depend on the time EMD638683 analyzed. Each of these issues was addressed above. Predictive methods previously developed by Ruhm (2016a) were extended and implemented to deal with the incompleteness of reporting. The involvement of drug combinations was carefully examined, with a distinction made between any versus exclusive drug involvement. Finally, a thorough investigation of the sensitivity of the results to the choice of analysis periods was provided. The findings have important implications. The number of U.S. residents dying from drug poisonings rose from 16,849 in 1999 to 47,055 in 2014. In all years analyzed, opioids were the most common class of drugs involved, justifying ongoing actions to reduce the negative consequences associated with their use. These efforts have met with some success: the number of fatal overdoses involving opioids declined 7% from 2011–2013 (from 24,271 to 22,501), before rising in 2014 (to 24,769). However, the total number of drug poisoning deaths has continued to grow, from 41,340 in 2011 to 47,505 in 2014, and fatal overdoses increased in every year since 1990, even as the involvement of specific drugs changed. For example, deaths involving cocaine fell 30% (from 10,133 to 7,131) from 2006–2014 whereas heroin-involved fatalities skyrocketed by 498% (from 2,360 to 14,103) between 2004–2014, with most of this growth since 2010. A key finding is that a majority of overdose fatalities involved multiple drug classes, complicating the attribution of the secular increase to specific drugs. Combination drug use itself is likely to be a risk factor. For example, sedatives were estimated to be involved in 11,843 deaths in 2014 versus just 1,847 in 1999, but were virtually never the only drug implicated. While the health risks of using benzodiazepines and opioids together are almost certainly greater than of either in isolation (Jones, Mogali & Comer, 2012; Park, Saitz, Ganoczy, Ilgen & Bohnert, 2015), the effects of interactions between drug types more generally remains poorly understood. This is an important area for future research. In addition, although the modest decline since 2011 in opioid-related mortality has been accompanied by an enormous increase in deaths involving heroin, the evidence is mixed on whether these are substitutes (Cicero, Ellis & Surratt, 2012; Markon & Crites, 2014; Powell, Pacula & Jacobson, 2015) or complements (Rudd et al., 2014; Compton, Jones & Baldwin, 2016). Attribution of the secular increase in fatal overdoses to specific drug categories also depended on the time period analyzed. Because deaths involving opioids rose extremely rapidly at the start of the 21st century (from 5,275 in 1999 to 22,015 in 2009), they were “responsible” for a large percentage of growth in drug poisoning fatalities for any period beginning at or near 1999, regardless of the ending year. Conversely, heroin played the most important role for periods starting after 2003, and even earlier when basing the calculations on exclusive drug involvement. This reflects the very rapid growth in heroin-related fatalities since the mid-2000s. However, the role of combination drug use is again worth emphasizing. It explained 40%-60% of the growth in drug deaths and became more important in recent years. The design of effective policies to reduce fatal drug poisonings therefore needs to reflect for the important role of drug cocktails.