Research Paper
A national case fatality study of drugs taken in intentional overdose

https://doi.org/10.1016/j.drugpo.2019.102609Get rights and content

Abstract

Background

Intentional drug overdose (IDO) has been linked with marked increases in premature mortality risk due to suicide, accidents and other causes, yet little is known about how case fatality risk varies according to the type of drug/s taken. This study aimed to examine the incidence of IDO, to identify the predictors of fatal IDO and to establish which drugs are linked with greater risk of a fatal outcome.

Methods

Data from the National Self-Harm Registry, and the National Drug-Related Deaths Index, 2007–2014, were used to calculate incidence, examine overdose characteristics and estimate case fatality risk ratios.

Results

We examined 63,831 non-fatal and 364 fatal IDOs (incidence: 148.8 and 1.01 per 100,000 respectively). Compared to non-fatal IDOs, fatal cases were more often male (55.2% vs. 42.0%), older in age (median 44 vs. 35 years), and more frequently involved multiple drugs (78.3% vs. 48.5%). Tricyclic antidepressants were associated with a 15-fold increased risk of death and opioids a 12-fold increased risk, relative to the reference category (non-opioid analgesics). While the risk of fatal outcome was higher for males than females, the elevation in risk was greater in females when tricyclic antidepressants or opioids were taken.

Conclusion

Male gender, increasing age and multiple drug use were associated with fatal IDO outcome. Tricyclic antidepressants and opioids were associated with a significantly increased risk of death following intentional overdose. Clinicians need to consider the case fatality risk of drugs when determining treatment for patients at risk of or those who have previously harmed themselves.

Introduction

Intentional drug overdose (IDO) is the most common method of hospital-presenting non-fatal self-harm (Perry et al., 2012; Vancayseele, Portzky & van Heeringen, 2016), and is associated with an increased risk of repeat self-harm (Finkelstein et al., 2016). The risk of mortality due to suicide is also increased among persons who have engaged in IDO, as are deaths due to other causes, including accidents and natural deaths caused by illness (Finkelstein et al., 2015a, ; 2015b).

Intentional drug overdose resulted in 7792 presentations to Irish hospitals in 2018 (Griffin et al., 2019), and accounts for approximately 68–84% of all hospital-treated self-harm presentations, most of which involve females and persons under 40 years of age (Daly et al., 2018; Vancayseele, Rotsaert, Portzky & van Heeringen, 2019). Fatal IDO results in approximately 40 deaths in Ireland annually (CSO, 2014), and accounted for approximately 889 deaths in England and Wales in 2018 (ONS, 2019), of which the majority are among males. Considering drugs taken, non-fatal IDOs most frequently involve non-opioid analgesics, antidepressants and hypnotic sedatives (including benzodiazepines) (Daly et al., 2018; Vancayseele et al., 2019), and fatal IDOs most commonly involve opioids and benzodiazepines (HRB, 2015; Pringle et al., 2017).

The type of drug taken in IDO varies according to individual characteristics, geography and across time periods, and is one of several key factors that influence the likelihood of repeat IDO and subsequent fatality following overdose (Finkelstein et al., 2016; Geulayov et al., 2018). Research in England and Wales, which measured case fatality of single-drug overdoses with antidepressants and benzodiazepines attributed high fatality to the antidepressants dosulepin, doxepin, citalopram (Hawton et al., 2010), and to the benzodiazepine and hypnotic drugs temazepam and zopiclone/zolpidem (Geulayov et al., 2018). A subsequent study in the USA examined the fatality of drugs used in all poisoning deaths (intentional and accidental) over a 16-year period, and identified opioids as the most toxic drug examined, followed by tricyclic antidepressants (Brett, Wylie, Raubenheimer, Isbister & Buckley, 2019).

Establishing the potential fatality of an IDO is undermined by the frequent involvement of a combination of multiple drugs in overdose. Multiple drugs are present in between 26 and 41% of non-fatal IDOs (Daly et al., 2018; Finkelstein et al., 2016), increasing to 64% in fatal overdoses (HRB, 2015). Despite the involvement of multiple drugs in IDO, the case fatality of drugs taken in multiple drug IDO remains under-researched and has not yet been established in relation to suicide deaths. Insights into the case fatality of drugs used in both single and multiple drug IDOs would aid clinicians in determining the appropriate treatment pathways for patients who are at increased risk of or have previously engaged in IDO.

This study aimed to estimate the incidence of fatal and non-fatal IDO, to identify the predictors of fatal IDO, and to establish which drug types are most strongly linked with a fatal outcome, according to case fatality risk estimates.

Section snippets

Method

This was an observational study using data pertaining to the period 1st Jan 2007 to 31st Dec 2014, which examined two unlinked datasets that captured fatal IDO cases in the National Drug-Related Deaths Index, Ireland (NDRDI) and non-fatal IDO presentations in the National Self-Harm Registry Ireland (NSHRI).

Characteristics of non-fatal and fatal IDOs

Between 1st January 2007 and 31st December 2014 there were 64,195 IDOs, 63,831 of which were non-fatal, and 364 of which were fatal. Of the fatal IDO cases, 46.2% (n = 168) had received a verdict of suicide and 53.8% (n = 196) an open verdict. The majority of fatal cases were male (55.2%) and the median age of these persons was 44 years (IQR: 33–53). Non-fatal IDO presentations were most often made by females (58.0%) and the median age reported was 35 years (IQR: 23–44). Multiple drug use was a

Main findings and interpretation

To our knowledge this is the first study which estimated case fatality risk associated with IDOs involving multiple drug types, which we examined using robust data from two national routinely collected datasets. We found that tricyclic antidepressants and opioid drugs are associated with a significantly increased risk of death following IDO, and this risk was greater in females than males when these drugs were taken. Male gender, increasing age and multiple drug use were found to be strong

Conclusion

Male gender, increasing age and multiple drug use were associated with fatal IDO. Tricyclic antidepressants and opioids were associated with significant elevations in risk of a fatal outcome following IDO. These findings add to the current evidence regarding the risk and potential adverse outcomes associated with these drugs, which informs safe and appropriate prescribing, where clinicians consider the fatality risk of drugs when determining treatment for patients at risk of self-harm or who

Conflict of Interest Statement

Caroline Daly, Eve Griffin, Roger T. Webb, Paul Corcoran, Ivan J. Perry and Ella Arensman have no conflicts of interest to disclose. Darren M. Ashcroft has, outside of the submitted work, received grants from Abbvie, Almirall, Celgene, Eli Lilly, Novartis, UCB and the Leo Foundation.

Acknowledgments

This research was supported by funding from the University of Manchester and the National Suicide Research Foundation, which is in receipt of funding from the National Office for Suicide Prevention, Ireland. The authors would like to acknowledge colleagues at the National Drug-Related Deaths Index for providing us with the fatal IDO and subsequent guidance on its use and interpretation. Furthermore, the authors would like to thank the Data Registration Officers for their important contribution

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