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Acute stressors and clinical characteristics differentiate death by suicide, accident, or natural causes among illicit and prescription opiate users
Drug and Alcohol Dependence 208 (2020) 107847
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Acute stressors and clinical characteristics differentiate death by suicide, accident, or natural causes among illicit and prescription opiate users
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Alison J. Atheya, Eleanor E. Bealea,*, James C. Overholsera, Craig A. Stockmeiera,b, Courtney L. Baggec,d a
Case Western Reserve University, Department of Psychological Sciences, Case Western Reserve University, 11220 Bellflower Road, Cleveland, OH, 44106-7123, USA University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Division of Neurobiology and Behavior Research, Translational Research Center (TR415), University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA c University of Michigan Medical Center, Department of Psychiatry, University of Michigan Medical Center, North Campus Research Center, B16, 2800 Plymouth Road Room 248E, Ann Arbor, MI, 48109-2800, USA d VA Ann Arbor Healthcare System, VA Center for Clinical Management Research (CCMR), 2215 Fuller Rd, Ann Arbor, MI, 48105, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Suicide Opiates Overdose
Background: Opiate misuse has reached epidemic levels. Prevention efforts depend on distinguishing opiate users from abusers. The current study compared opioid users who died by natural cases, accidents, and suicide using psychological autopsy methods. Groups were compared on substance use characteristics, treatment history, experiences of negative life events, and circumstances at the time of death. Methods: Substance use and suicide risk were evaluated using psychological autopsy methods in 63 decedents with positive toxicology for opiates at death divided into three groups: adults dying by suicide (n = 19), accident (n = 19), and natural causes (n = 25). Groups were compared on several dependent measures, using chi-square analyses to examine categorical variables and one-way analyses of variance (ANOVA) to examine continuous variables. Results: Individuals who died by suicide were similar in many ways to adults who died by an accidental overdose. However, suicide completers were more likely to have struggled with severe depression, and previously attempted suicide, whereas the accidental overdose sample was more likely to display a chronic pattern of severe drug abuse. Conclusions: The current study helps to distinguish between opiate users who are at risk for death by an accidental or intentional overdose. In the ongoing opiate crisis, clinicians must understand the risk of overdose and the nuances of accidental behaviors compared to purposeful ones. Signs of suicidal planning, relevant psychopathology, and ongoing life stress may be useful points of intervention for stopping the increasing number of deaths among opiate users.
1. Introduction Prescription (Calcaterra et al., 2013; Cerdá et al., 2013) and illicit (Calcaterra et al., 2013; Cerdá et al., 2013) opioid use is on the rise internationally. As many as 11.8 million Americans over the age of 12 misuse any form of opiates, with the majority misusing prescription opiates (N = 10.9 million; (Bose et al., 2018). Heroin (Lopez-Quintero et al., 2015), other intravenous drug use (Artenie et al., 2015), and polysubstance misuse and dependence (Artenie et al., 2015) have consistently been identified as risk factors for accidental and suicidal overdose. Recent research indicates that prescription opioid use is also associated with premature mortality due to accidental overdose
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(Calcaterra et al., 2013) and suicide (Austin et al., 2017). Opiate users die prematurely from any cause, natural causes, accidents, and suicide (Pierce et al., 2015). The initial use of opiate medication is often initiated by the presence of chronic pain. Chronic pain and depression are often related and when both problems occur, substance abuse is common (Madadi and Persaud, 2014). In the 12 months following a nonfatal opioid overdose, there is a significantly elevated risk of dying from a variety of medical problems (Olfson et al., 2018). Furthermore, there is an important connection between opiate use and suicide. In a national survey of more than 41,000 adults across the US, the abuse of prescription opiate medication has been found to be associated with suicidal ideation,
Corresponding author at: Department of Psychological Sciences, Case Western Reserve University, 11220 Bellflower Road, Cleveland, OH, 44106-7123, USA. E-mail address: [email protected] (E.E. Beale).
https://doi.org/10.1016/j.drugalcdep.2020.107847 Received 15 September 2019; Received in revised form 29 December 2019; Accepted 31 December 2019 Available online 11 January 2020 0376-8716/ © 2020 Published by Elsevier B.V.
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suicidal ideation, suicidal intent, or suicidal planning. It was predicted that cases of death by suicide would be related to prominent symptoms of depression and more severe life stress. Our analyses focused on opioid users who had positive opioid toxicology screens at the time of death, rather than individuals who were diagnosed with opioid use disorders prior to death, since a range of opioid misuse may increase mortality (Ilgen et al., 2016). Nationally representative studies indicate that both opioid use disorders (Pierce et al., 2015) and opioid misuse (Ashrafioun et al., 2017) are associated with significant increases in risk for premature death and other highrisk behaviors (Mojtabai, 2018). Focusing research on individuals who suffer from opiate use disorders may underestimate the effects of opiates on premature mortality.
suicide planning, and suicide attempts (Ashrafioun et al., 2017). Furthermore, in recent years, opioid use has become more frequently noted in the toxicology results of individual who die by suicide (Braden et al., 2017). Among opiate users, intentional and accidental overdose are distinct events (Bohnert and Ilgen, 2019; Britton et al., 2012). Distinguishing factors may include the presence of depression, anxiety, or personality pathology (Maloney et al., 2009). High levels of opiate use are related to increased risk of suicide, not limited to intentional drug overdose (Ilgen et al., 2016). It has been estimated that 20–30 % of deaths by opioid overdose are best classified as suicides (Oquendo and Volkow, 2018). Prevention efforts depend on identifying which opiate users are at risk of dying by medical complications, accidental overdose, or suicide. Identifying a profile of risk for premature death in high-risk populations like opiate users may be difficult. There are some indications that accidental opiate overdoses and suicide by opiate overdose have been misclassified in recent epidemiologically-based research (Rockett et al., 2018). Epidemiological research can only offer clues about national level risk-factors for opioid-related mortality if medical examiners are able to correctly classify the manner of death in national death reporting surveillance systems. Research evaluating suicide decedents is limited (Ribeiro et al., 2018) and little is known about factors which differentiate individuals who die by suicide from those who die by accidental overdose. Clinical (Hakansson and Gerle, 2018) and forensic (Stone et al., 2017) psychologists have called for the use of psychological autopsy evaluations of premature deaths among opioid users. Post-mortem research has evaluated large, nationally or regionally representative databases containing information about decedents with opioid use disorders or opioid prescriptions. Differentiating accidental overdoses from suicide by overdose may be complicated in post-mortem research (Rockett et al., 2018) when information about suicidal intent is limited. Psychological autopsy methodologies may enhance population-wide analyses because they integrate autopsy reports, police death scene investigations, medical and psychiatric record review, and interviews with decedents’ family members. While psychological autopsy studies cannot account for decedents’ subjective experience, validated postmortem methodologies can be used to characterize decedents’ functioning prior to death and evaluate manner of death (Conner et al., 2011; Connor et al., 2012). By definition, suicidal intent differentiates deaths by intentional overdose from deaths by accidental overdose. Opioid use disorders and prescription opioid misuse are independently associated with an increased risk of suicidal ideation, planning, and attempts when adjusting for physical and mental health conditions (Ashrafioun et al., 2017). Suicidal intent may be a continuous, multi-faceted, or dynamic construct. Most subjects reported ambivalence about suicidal intent following an opioid overdose (Neale, 2000). Illicit drug use is significantly related to non-fatal suicide attempts but not suicidal ideation in multivariate analyses controlling for psychiatric diagnoses (Ashrafioun et al., 2015). Thus, it is possible that individuals who die by accidental and intentional overdose cannot be categorized based on evidence of suicidal ideation or suicidal intent prior to death. The primary aim of the present study was to extend the post-mortem opioid literature by using psychological autopsy research to compare opioid users who died by natural causes, accidents, and suicide. We compared subjects on characteristics which have been shown to increase risk of morbidity or mortality in nationally representative studies of decedents. Specifically, we evaluated between-group differences in demographic background, clinical and substance use characteristics, and treatment history. We also compared subjects’ experiences of negative life events leading up to death. This study assessed circumstances at the time of death which differentiate risk of death by accident, suicide, or natural causes among opiate users. We evaluated whether opioid users who died by suicide or accident showed differences in beliefs about death, preparation for life-threatening behaviors or death,
2. Materials and methods 2.1. Subjects Substance use and suicide risk were evaluated in 63 decedents with positive toxicology results for opiates at death. Subjects were collected from a broader IRB-approved research study looking at factors associated with completed suicide of individuals who died in Cuyahoga County, Ohio, during the years 1989–2017 (Overholser et al., 2012). A next-of-kin informant was recruited by the research team to be consented and interviewed concerning the deceased individual, and all available collateral information, such as medical examiner’s reports, police reports, legal records, medical/psychiatric records, were collected with a release of information from the next-of-kin. Next-of-kin included parents, spouses, siblings, extended family members, and friends, with the most common relationships being parent or spouse. In the current study, subjects were divided into three groups based on the Medical Examiner’s classification of death: adults dying by suicide (n = 19), accident (n = 19), and natural causes (n = 25). Of note, all but one accidental death (n = 18) died of an opiate overdose. 2.2. Measures The Structured Interview for DSM-IV (SCID) is a structured diagnostic assessment which was used to identify Axis I disorders among decedents (First et al., 1995). SCID items were adapted for psychological autopsy such that they referred to symptoms experienced by the study subjects and not the informants. In addition to informant reports, SCID items were rated based on psychiatric, medical, and legal records. SCID interviews provided detailed information about the duration and severity of major mental illness for the deceased. The SCID shows excellent psychometric properties in psychological autopsy research. High levels of agreement are observed between participant and informant report on the SCID (Kappa = 0.68, mean Kappa = 0.74, range = 0.65 – 0.87; (Schneider et al., 2004). Suicide attempters and family member informants show an excellent level of concordance on the SCID (Kappa = 1.0; (DeJong and Overholser, 2009). Inter-rater reliability is in the excellent range among proxy informants for suicide decedents and agematched controls (Kappa = 0.96–1.0; (Dumais et al., 2005). The Structured Interview for DSM-IV Personality Disorders (SIDPIV) is a semi-structured, valid and reliable diagnostic assessment used to identify DSM-IV Axis II disorders (Pfohl et al., 1997). The SIDP-IV was adapted for psychological autopsy such that items referred to decedents, collateral records supplemented interviews, and consensus diagnosis procedures were used. Standardized questions assessed the presence and severity of dysfunction in domains ranging from social relationships, unusual thinking patterns (e.g., paranoia), self-perception, emotionality, and impulsivity that last for at least five years prior to death. Unusual patterns of personality functioning, such as those exhibited during hospitalization or episodic mental illnesses (e.g., mania), were excluded. Items were rated on four-point Likert type scale with ratings 0 (not present) to 3 (strongly present: the behavior or 2
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characteristic was persistently present over 5 years and caused significant impairment in functioning or distress). The SIDP-IV domain scores can be aggregated to provide dimensional ratings of personality pathology (Pfohl et al., 1997). Psychometric analysis of SIDP-IV diagnosis based on proxy-report indicates that rates of concordance are in the good to excellent range when consensus diagnosis procedures are used (Bernstein et al., 1997). The Modified Life Experiences Scale (MLES) is an 11-item measure of potentially stressful life events experienced in the time proximal or distal to suicide or natural death. In the present study, the presence of ten categories of stressors within three months of death were assessed using the MLES. The measure was derived from the Life Experiences Survey (LES; (Sarason et al., 1978) which shows good to excellent rates of test-retest reliability (r = .64) over a 5- to 6-week interval. The MLES has been used successfully in psychological autopsy research (Fisher and Overholser, 2014; Overholser et al., 2012). The Suicide Intent Scale – Planning Subscale (SIS-P) is a 7-item measure of suicidal planning and preparation for death which was adapted from Beck’s Suicide Intent Scale (Beck et al., 1974). Scores can range from 0 to 14, with higher scores reflecting elevated levels of premeditation for death. The measure was used with all subjects in the present study (including subjects who died by accident and natural causes). The circumstances of death for all subjects were evaluated for higher or lower levels of planning or suicidal ideation at the time of death. An acceptable level of internal consistency (α = .76) was observed in the 7-item scale used here.
Table 1 Demographics and diagnostic characteristics of decedents with positive postmortem opiate toxicology results (N = 63).
2.3. Procedures
Participants who died by accident were more likely than other decedents to have a history of opiate use disorder (χ² (N = 63) = 7.81, p = .02; accident: 52.6 %; suicide: 15.8 %; natural: 20.0 %) and alcohol use disorder (χ² (N = 63) = 10.58, p = .005; accident: 84.2 %; suicide: 47.4 %; natural: 36.0 %). Perhaps as a result of the increased prevalence of prescription substance use disorders involving antidepressant medications, polysubstance use disorders were more common among subjects who died by accident (χ² (N = 62) = 6.04, p = .049; accident: 42.1 %; suicide: 15.8 %; natural: 12.0 %). Opiate users showed no differences in risk for nicotine use disorder (accident: 64.7 %; suicide: 61.1 %; natural: 52.0 %) and other substance use disorders were too infrequent to conduct meaningful analysis. Subjects who died by accident were significantly more likely to have a prior accidental opiate overdose than subjects who died by suicide or natural causes (χ² (N = 61) = 8.65, p = .01; Table 2). Compared to opiate users who died by other causes, opiate users who died by accident were significantly more likely to have illicit (vs. prescribed) forms of opiates in their postmortem toxicology (χ² (N = 57) = 7.07, p = .03). The three groups of opiate users showed no difference in their typical method of opiate use (pill or other form), and were similar in the age of onset of opiate use and the number of years using opiates. Subjects identified as using opiates who died by accident did not appear to show a different set of risk factors for opiate use compared to subjects who died by natural causes or suicide. Subjects who died by accident, suicide, and natural causes showed similar rates of serious medical problems including chronic pain conditions, medical conditions, and inpatient medical hospitalization in the six months before death. We observed similar rates of homelessness, legal issues, and incarceration within six months of death among the groups of opiate users, and similar rates of potentially protective factors against complications of opiate use including lifetime and recent inpatient psychiatric treatment, lifetime substance use treatment, and the use of drug replacement therapy. Subjects who died by accidental death were significantly more likely to experience the stress related to conflict with a family member when compared to opiate users who died by suicide or natural causes (χ² (N = 61) = 8.17, p = .02). We observed similar rates of conflict with parents, spouses, children, and friends between the groups of opiate users.
Age M (SD) Male gender White race Married > High school diploma Employed Major depression Bipolar disorder Anxiety disorder Posttraumatic stress disorder Psychotic disorder Any personality disorder
Suicidal Death (n = 19)
Accidental Death (n = 19)
Natural Cause Death (n = 25)
Test Statistic
p-value
50.26 (18.90) 73.70 94.70 42.10 42.10
42.42 (12.37) 84.20 94.70 26.30 31.60
50.68 (15.33) 48.00 88.00 56.00 48.00
1.76
.18
6.97* 0.94 3.89 1.21
.03 .63 .14 .55
31.60 63.20 0.00 10.50 10.50
52.60 21.10 5.30 15.80 10.50
36.00 40.00 4.00 12.00 4.00
2.39 6.98* 0.95 2.87 0.88
.30 .03 .62 .24 .64
0.00 31.60
5.30 52.60
4.00 28.00
0.95 3.76
.62 .15
M = Mean; SD = Standard deviation. Note: Data are reported as % unless otherwise specified. All test-statistics reported are chi-square values except for age with is reported as an F-value for ANOVA. * p-value < .05.
Psychological autopsy procedures evaluated cause of death, psychological diagnoses, and psychosocial characteristics. Written informed consent was obtained from legally-defined next-of-kin for informant-based retrospective diagnostic interviews. All assessment procedures followed the guidelines for psychological autopsy research (Hawton et al., 1998). Informant interviews were used to evaluate the presence, duration, and severity of psychological symptoms. Interviews were typically conducted approximately six months after the death of study subjects in order to reduce the effects of memory decay or possible risks of exacerbating bereavement (Connor et al., 2012). Interviews were supplemented by medical examiner’s reports, medical records, psychiatric records, and police reports. Collateral documentation was used to evaluate the reliability of information provided by informants and to support data collection. An extensive report detailing all of the information gathered during the interview session was created by a trained social worker. All records were reviewed by a board certified psychiatrist, a board certified clinical psychologist, a master's level social worker, and a neuroscientist to confirm item-level data and diagnoses. The consensus report was reviewed by each mental health professional prior to a review meeting (Ebert, 1987). 2.4. Data analysis The suicide, accidental death, and natural death groups were compared on several dependent measures, using chi-square to examine categorical variables and one-way analyses of variance (ANOVA) to examine continuous variables. 3. Results 3.1. Accidental deaths Men were significantly over-represented in the group of opiate users who died by accident than in other groups (χ² (N = 63) = 6.97, p = .03; Table 1). Opiate users who died by accident, suicide, and natural causes were similar in terms of age, race, marital status, educational attainment, and employment status at the time of death. 3
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Table 2 Substance use characteristics of decedents with positive post-mortem opiate toxicology results (N = 63).
Age of onset of opiate use M (SD) Duration of opiate use M (SD) Oral method of opiate use Chronic pain conditions Homelessness Incarceration Substance use treatment Use of drug replacement therapy Prior unintentional overdose Illicit opiates in post-mortem toxicology
Suicidal Death (n = 19)
Accidental Death (n = 19)
Natural Cause Death (n = 25)
Test Statistic
p-value
32.16 (21.38) 5.60 (5.75) 68.40 52.60 0.00 26.30 31.60 5.30 5.30 36.84
36.21 (13.48) 6.35 (8.04) 57.90 68.40 5.30 21.10 47.40 5.30 26.30 66.67
39.57 (15.73) 6.50 (9.92) 60.00 72.00 4.00 8.00 20.00 0.00 4.00 25.00
0.60 0.04 0.48 1.92 0.95 3.09 3.71 2.30 8.65* 7.07*
.55 .96 .79 .38 .62 .21 .16 .32 .01 .03
M = Mean; SD = Standard deviation. Note: Data are reported as % unless otherwise specified. All test-statistics reported are chi-square values except for age and duration which are reported as F-values for ANOVA. * p-value < .05.
3.2. Death by suicide
3.3. Sensitivity analysis
Opiate users who were suicide decedents were more likely than subjects that had accidental or natural deaths to have any depressive disorder (χ² (N = 63) = 10.66, p = .005), including major depressive disorder (χ² (N = 63) = 6.98, p = .03). The three groups of opiate users showed similar rates of bipolar disorder, anxiety disorders, posttraumatic stress disorder, psychotic disorders, and personality disorders. None of the three groups differed in having a history of non-fatal suicide attempts. However, suicide decedents had a higher number of prior suicide attempts than those who died by natural causes (F(2, 44) = 4.52, p = .02; Tukey HSD p = .02). Opiate users who died by accident experienced a similar number of non-fatal suicide attempts as opiate users who died by suicide and natural causes. Suicide decedents showed the highest average number of lifetime stressors compared to other opiate users who died by accident or natural causes (F(2, 57) = 4.33, p = .02). The number of stressors experienced by suicide decedents was significantly higher than those experienced by opiate users who died by natural causes (p = .01). Suicide decedents were significantly more likely to experience the end of a romantic relationship in the six months prior to death when compared to other groups (χ² (N = 61) = 6.97, p = .03). No differences were observed between the groups of opiate users in the rate of recent divorces or marital separations. Opiate users who died by suicide and accidents showed similarities in the rates at which they experienced most other stressors in the six months before death. No differences were observed in the rate at which subjects who died by suicide or accident experienced recent bereavement, financial problems, occupational difficulties or unemployment, or the hospitalization of family members. Opiate users who died by suicide showed higher levels of recent planning for death (SIS-P score; F(2, 57) = 43.43, p < .001) than individuals died by accidental or natural causes. Suicide decedents showed significantly higher levels of preparation for death than the other groups of opiate users in all areas including isolation at time of death (F(2, 53) = 7.45, p = .001), timing self-harm to increase the likelihood of death (F(2, 52) = 6.17, p = .004), taking precautions to prevent interruption during opiate use or suicide (F(2, 54) = 8.91, p < .001), taking final acts in anticipation of death F(2, 55) = 7.77, p = .001), or preparation for potentially lethal self-harm (F(2, 56) = 19.95, p < .001). Only suicide decedents vocalized thoughts of death (F (2, 58) = 12.77, p < .001) or completed suicide notes (F(2, 60) = 12.22, p < .001) in the time before death.
In order to clarify our original analyses, we conducted sensitivity analyses to determine if our initial results accurately described differences specifically between death by suicide and death by accidental opiate overdose among opiate users. Given our smaller number of subjects per group, we decided to execute this as a sensitivity analysis rather than the main results. For this analysis, we excluded data from opiate users who died by natural death (n = 25) and subjects who died by accidental causes other than accidental overdose (n = 1), only including opiate users who died by accidental causes if they died by overdose (n = 18). Finally, we repeated the analyses comparing opiate users who died by any form of suicide, including 5 subjects who died by opiate overdose (26.3 %). The findings provided further support to our central aim of comparing risk for morbidity and mortality among opiate users across different types of death and the corresponding results. The pattern of results which emerged from comparing accidental overdose deaths to suicides was remarkably similar to the analyses comparing opiate users who died by natural causes, accidents, and suicide. No demographic differences emerged between subjects who died by accidental overdose or suicide. The chi-square analysis which suggested that subjects who died by accidental overdose were more likely than suicide decedents to have polysubstance use disorders was reduced to a non-significant trend (χ² (N = 37) = 3.63, p = .06). No differences emerged in the number or kind of stressful life events in sensitivity analyses comparing subjects who died by accidental overdose and suicide. In the sensitivity analysis, differences were observed between the group of subjects who died by accidental opiate overdose and those who died by suicide in the average number of prior non-fatal suicide attempts in the sensitivity analysis. Subjects who died by suicide had a significantly higher number of non-fatal suicide attempts (M = .47, SD = .51) than subjects who died by accidental overdose (M = .09, SD = .30; F(1, 26) = 4.87, p = .04). No other comparisons differed from the results found in the main analyses. 4. Discussion The present results suggest that opiate users who die by suicide and by accident show separate, but partially overlapping risk profiles. Opiate users who die from preventable manners of death are different from opiate users who die by natural causes (i.e. those who receive prescription medication in hospital settings). Individuals with serious mental illness are at a heightened risk of death relating to purposeful and accidental overdose from opiate misuse. Individuals with serious mental illness are significantly more likely to experience opiate use disorders and to develop suicidal ideation in the context of co-occurring opiate-use and sedative-use disorders (Spivak et al., 2018). The present 4
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and their family member informants (DeJong and Overholser, 2009). With postmortem research, the cause of death is not always clear, and the medical examiner must rely on an integration of various sources of information when determining cause of death (Byard, 2008). With the current increase in deaths related to opioid overdose, it can become challenging to decide if a person died by intentional or accidental causes. A recent study (Liu et al., 2019) found that mathematical models can help to provide more accurate estimates of international overdose, especially when suicide rates have been underreported. However, a thorough evaluation conducted by a qualified medical examiner integrates many sources of information to make the final determination (Gill et al., 2013). Furthermore, forensic examiners are quite accurate even without conducting an autopsy, and cause of death rulings can be trusted when based on a thorough forensic autopsy examination (Nashelsky and Lawrence, 2003). There is limited research comparing death type among opiate users, and the present findings are limited by small samples collected postmortem. Few available models predict risk for suicide among opiate users, much less the specific form of premature death in high-risk groups. Many opioid users experience both non-fatal suicide attempts and truly accidental overdoses (Rossow and Lauritzen, 1999). Risk factors for accidental overdose and non-fatal suicide attempts may also overlap (Bohnert et al., 2010). Opioid users who experience non-fatal overdoses and non-fatal suicide attempts may represent a complex population at risk of fatal outcomes. Research with populations who have experienced opioid related morbidity may provide insight into cognitive and affective risk factors for fatal outcomes. The current results help to identify potential targets for assessment among opiate users. In the current opiate crisis, it is imperative that clinicians understand the nuances of potential overdose and how accidental behaviors can be distinguished from purposeful ones. Opiate users overall are at high suicide risk. Although a history of suicidal behavior is common between individuals who die accidentally and those who die by suicide, there is an important distinction in the degree of planning for death. Early intervention may focus on awareness of suicidal planning, addressing the relevant psychopathology, and targeting ongoing life stress. It may be possible to reduce the risk of death by understanding what factors lead some opiate users toward a suicidal crisis.
results show that as compared to cases of natural death, opiate users who die by accident were significantly more likely to be male and to have a history of opiate, alcohol, or polysubstance use disorder. Thus, adults who die by accidental death show stronger patterns of substance abuse than found in opiate users who die by suicide. Higher levels of alcohol use are associated with higher risk for suicide attempt (Borges et al., 2016). When combined with other drugs, alcohol creates a synergistic risk for suicide attempts (Bagge and Borges, 2017) and death by suicide (Kõlves et al., 2017). In the present study, opioid users who died by accident had higher rates of alcohol use disorder (84.2 %) and alcohol in their system in their toxicology at autopsy (42.1 %) as compared to opiate users who died from suicide (alcohol use disorder = 47.4 %; alcohol toxicology = 26.3 %). The use and abuse of alcohol can play a role in a broad spectrum of causes of death. Acute intoxication can be used to facilitate a suicide attempt (Bagge et al., 2015), perhaps by lowering a person's inhibitions and impairing rational thinking, potentially resulting in impulsive and dangerous acts. The risk of suicidal behavior is increased in proportion to the amount of alcohol consumed during the previous 6 h (Borges et al., 2016). Future research may begin to disaggregate the influence of acute and chronic substance use on intentional and unintentional causes of death. In the present study, opiate users who died by accidental causes were more likely to have a prior accidental overdose, to have opiates in their blood at time of death, and to experience conflict with an extended family member. In comparison, opiate users who died by suicide were more likely to meet criteria for any depressive disorder, a major depressive disorder, and to have experienced a higher number of lifetime stressors. These suicidal individuals also showed more planning and preparation for death than the other two groups. Number of prior suicide attempts was similar between individuals in the accidental and suicide death groups, while those who died by suicide had a higher number of previous attempts compared to those who died by natural causes. Overall, accidental overdose and suicide in opiate users presented separate categories of high-risk behaviors sharing common vulnerabilities while both differed from opiate users who died by natural causes. Substance users die at a younger age than the general population, especially when the cause of death is suicide or accident (Stenbacka et al., 2010). Opiate users may be vulnerable to various forms of premature death (Case and Deaton, 2015), especially when they are not involved with treatment (Peles et al., 2013). Suicidal planning at the time of death, but not a prior suicide attempt, may be related to risk for suicide. In contrast, a history of opiate overdose may be related to risk of accidental death among opiate users. Acute stressors and prior nonfatal suicide attempts are common among high-risk groups and may not be specific enough to distinguish risk. Accidental deaths in opiate users seem to follow repeated, non-fatal overdose as well as other high-risk substance use behaviors. In contrast, suicide deaths in opiate users seem to occur in the context of depression. In prior research, a history of non-fatal suicide attempts did not differentiate risk of suicide from risk of accidental overdose (Ribeiro et al., 2016). However, the suicide decedents in our sample showed higher levels of planning for death than individuals who had accidental and natural deaths. The current study had several of limitations. Stressful life events were rated for their categorical presence or absence. The timing (Bagge et al., 2013) and magnitude (Buchman-Schmitt et al., 2017) of stressful life events can affect suicide risk (Bagge et al., 2013). Furthermore, because of the nature of psychological autopsy research, the present study was unable to evaluate the subjective impact of negative life events. However, postmortem research often includes access to information that is not readily available in self-report surveys, including family views, medical records, suicide notes, police records, and toxicology results. Furthermore, prior research has found a high level of agreement on diagnostic questions posed to suicidal psychiatric patients
Role of funding source Nothing declared. Declaration of Competing Interest No conflict declared. Contributors Alison J. Athey, M.A. declares that she materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Eleanor E. Beale, B.A. declares that she materially participated in the data analysis and article preparation for the current manuscript and has approved the final article. James C. Overholser, Ph.D. declares that he materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Craig A. Stockmeier, Ph.D. declares that he materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Courtney L. Bagge, Ph.D. declares that she materially participated in the data analysis and article preparation for the current manuscript and has approved the final article. 5
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This work was supported by grants from the National Institute of Mental Health (MH67996) and the IDeA/COBRE Program of NIGMS (P30 GM103328). Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.drugalcdep.2020. 107847. References Artenie, A.A., Jutras‐Aswad, D., Roy, É, Zang, G., Bamvita, J.M., Lévesque, A., Bruneau, J., 2015. Visits to primary care physicians among persons who inject drugs at high risk of hepatitis C virus infection: room for improvement. J. Viral Hepat. 22, 792–799. Ashrafioun, L., Bishop, T.M., Conner, K.R., Pigeon, W.R., 2017. Frequency of prescription opioid misuse and suicidal ideation, planning, and attempts. J. Psychiatr. Res. 92, 1–7. Ashrafioun, L., Bohnert, A.S., Jannausch, M., Ilgen, M.A., 2015. Evaluation of the current opioid misuse measure among substance use disorder treatment patients. J. Subst. Abuse Treat. 55, 15–20. Austin, A.E., Proescholdbell, S.K., Creppage, K.E., Asbun, A., 2017. Characteristics of selfinflicted drug overdose deaths in North Carolina. Drug Alcohol Depend. 181, 44–49. Bagge, C.L., Borges, G., 2017. Acute substance use as a warning sign for suicide attempts: a case-crossover examination of the 48 hours prior to a recent suicide attempt. J. Clin. Psychiatry 78, 691–696. Bagge, C.L., Conner, K.R., Reed, L., Dawkins, M., Murray, K., 2015. Alcohol use to facilitate a suicide attempt: an event-based examination. J. Stud. Alcohol Drugs 76, 474–481. Bagge, C.L., Glenn, C.R., Lee, H.J., 2013. Quantifying the impact of recent negative life events on suicide attempts. J. Abnorm. Psychol. 122, 359. Beck, A.T., Weissman, A., Lester, D., Trexler, L., 1974. The measurement of pessimism: the hopelessness scale. J. Consult. Clin. Psychol. 42, 861. Bernstein, D.P., Kasapis, C., Bergman, A., Weld, E., Mitropoulou, V., Horvath, T., Klar, H.M., Silverman, J., Siever, L.J., 1997. Assessing Axis II disorders by informant interview. J. Personal. Disord. 11, 158–167. Bohnert, A.S., Ilgen, M.A., 2019. Understanding links among opioid use, overdose, and suicide. N. Engl. J. Med. 380, 71–79. Bohnert, A.S., Roeder, K., Ilgen, M.A., 2010. Unintentional overdose and suicide among substance users: a review of overlap and risk factors. Drug Alcohol Depend. 110, 183–192. Borges, G., Cherpitel, C.J., Orozco, R., Ye, Y., Monteiro, M., Hao, W., Benegal, V., 2016. A dose–response estimate for acute alcohol use and risk of suicide attempt. Addict. Biol. 22, 1554–1561. Bose, J., Hedden, S.L., Lipari, R.N., Park-Lee, E., Tice, P., 2018. Key Substance Use and Mental Health Indicators in the United States: Results From the 2017 National Survey on Drug Use and Health. Retrieved from https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHFFR2017/NSDUHFFR2017.pdf. Accessed on December 11, 2019. . Braden, J.B., Edlund, M.J., Sullivan, M.D., 2017. Suicide deaths with opioid poisoning in the United States: 1999–2014. Am. J. Public Health 107, 421–426. Britton, P.C., Bohnert, A.S., Wines Jr, J.D., Conner, K.R., 2012. A procedure that differentiates unintentional from intentional overdose in opioid abusers. Addict. Behav. 37, 127–130. Buchman-Schmitt, J.M., Chu, C., Michaels, M.S., Hames, J.L., Silva, C., Hagan, C.R., Ribeiro, J.D., Selby, E.A., Joiner, T.E., 2017. The role of stressful life events preceding death by suicide: evidence from two samples of suicide decedents. Psychiatry Res. 256, 345–352. Byard, R.W., 2008. Forensic pathology and problems in determining cause of death. Am. J. Forensic Med. Pathol. 4. Calcaterra, S., Glanz, J., Binswanger, I.A., 2013. National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999–2009. Drug Alcohol Depend. 131, 263–270. Case, A., Deaton, A., 2015. Rising morbidity and mortality in midlife among white nonHispanic Americans in the 21st century. Proc. Natl. Acad. Sci. U. S. A. 112, 15078–15083. Cerdá, M., Ransome, Y., Keyes, K.M., Koenen, K.C., Tracy, M., Tardiff, K.J., Vlahov, D., Galea, S., 2013. Prescription opioid mortality trends in New York City, 1990–2006: examining the emergence of an epidemic. Drug Alcohol Depend. 132, 53–62. Conner, K.R., Beautrais, A.L., Brent, D.A., Conwell, Y., Phillips, M.R., Schneider, B., 2011. The next generation of psychological autopsy studies: part I, interview content. Suicide Life. Behav. 41, 594–613. Connor, K.R., Beautrais, A.L., Brent, D., Conwell, Y., Phillips, M., Schneider, B., 2012. The next generation of psychological autopsy studies: part II, interview procedures. Suicide Life. Behav. 42, 86–103. DeJong, T.M., Overholser, J.C., 2009. Assessment of depression and suicidal actions:
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Full length article
Acute stressors and clinical characteristics differentiate death by suicide, accident, or natural causes among illicit and prescription opiate users
T
Alison J. Atheya, Eleanor E. Bealea,*, James C. Overholsera, Craig A. Stockmeiera,b, Courtney L. Baggec,d a
Case Western Reserve University, Department of Psychological Sciences, Case Western Reserve University, 11220 Bellflower Road, Cleveland, OH, 44106-7123, USA University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Division of Neurobiology and Behavior Research, Translational Research Center (TR415), University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA c University of Michigan Medical Center, Department of Psychiatry, University of Michigan Medical Center, North Campus Research Center, B16, 2800 Plymouth Road Room 248E, Ann Arbor, MI, 48109-2800, USA d VA Ann Arbor Healthcare System, VA Center for Clinical Management Research (CCMR), 2215 Fuller Rd, Ann Arbor, MI, 48105, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Suicide Opiates Overdose
Background: Opiate misuse has reached epidemic levels. Prevention efforts depend on distinguishing opiate users from abusers. The current study compared opioid users who died by natural cases, accidents, and suicide using psychological autopsy methods. Groups were compared on substance use characteristics, treatment history, experiences of negative life events, and circumstances at the time of death. Methods: Substance use and suicide risk were evaluated using psychological autopsy methods in 63 decedents with positive toxicology for opiates at death divided into three groups: adults dying by suicide (n = 19), accident (n = 19), and natural causes (n = 25). Groups were compared on several dependent measures, using chi-square analyses to examine categorical variables and one-way analyses of variance (ANOVA) to examine continuous variables. Results: Individuals who died by suicide were similar in many ways to adults who died by an accidental overdose. However, suicide completers were more likely to have struggled with severe depression, and previously attempted suicide, whereas the accidental overdose sample was more likely to display a chronic pattern of severe drug abuse. Conclusions: The current study helps to distinguish between opiate users who are at risk for death by an accidental or intentional overdose. In the ongoing opiate crisis, clinicians must understand the risk of overdose and the nuances of accidental behaviors compared to purposeful ones. Signs of suicidal planning, relevant psychopathology, and ongoing life stress may be useful points of intervention for stopping the increasing number of deaths among opiate users.
1. Introduction Prescription (Calcaterra et al., 2013; Cerdá et al., 2013) and illicit (Calcaterra et al., 2013; Cerdá et al., 2013) opioid use is on the rise internationally. As many as 11.8 million Americans over the age of 12 misuse any form of opiates, with the majority misusing prescription opiates (N = 10.9 million; (Bose et al., 2018). Heroin (Lopez-Quintero et al., 2015), other intravenous drug use (Artenie et al., 2015), and polysubstance misuse and dependence (Artenie et al., 2015) have consistently been identified as risk factors for accidental and suicidal overdose. Recent research indicates that prescription opioid use is also associated with premature mortality due to accidental overdose
⁎
(Calcaterra et al., 2013) and suicide (Austin et al., 2017). Opiate users die prematurely from any cause, natural causes, accidents, and suicide (Pierce et al., 2015). The initial use of opiate medication is often initiated by the presence of chronic pain. Chronic pain and depression are often related and when both problems occur, substance abuse is common (Madadi and Persaud, 2014). In the 12 months following a nonfatal opioid overdose, there is a significantly elevated risk of dying from a variety of medical problems (Olfson et al., 2018). Furthermore, there is an important connection between opiate use and suicide. In a national survey of more than 41,000 adults across the US, the abuse of prescription opiate medication has been found to be associated with suicidal ideation,
Corresponding author at: Department of Psychological Sciences, Case Western Reserve University, 11220 Bellflower Road, Cleveland, OH, 44106-7123, USA. E-mail address: [email protected] (E.E. Beale).
https://doi.org/10.1016/j.drugalcdep.2020.107847 Received 15 September 2019; Received in revised form 29 December 2019; Accepted 31 December 2019 Available online 11 January 2020 0376-8716/ © 2020 Published by Elsevier B.V.
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suicidal ideation, suicidal intent, or suicidal planning. It was predicted that cases of death by suicide would be related to prominent symptoms of depression and more severe life stress. Our analyses focused on opioid users who had positive opioid toxicology screens at the time of death, rather than individuals who were diagnosed with opioid use disorders prior to death, since a range of opioid misuse may increase mortality (Ilgen et al., 2016). Nationally representative studies indicate that both opioid use disorders (Pierce et al., 2015) and opioid misuse (Ashrafioun et al., 2017) are associated with significant increases in risk for premature death and other highrisk behaviors (Mojtabai, 2018). Focusing research on individuals who suffer from opiate use disorders may underestimate the effects of opiates on premature mortality.
suicide planning, and suicide attempts (Ashrafioun et al., 2017). Furthermore, in recent years, opioid use has become more frequently noted in the toxicology results of individual who die by suicide (Braden et al., 2017). Among opiate users, intentional and accidental overdose are distinct events (Bohnert and Ilgen, 2019; Britton et al., 2012). Distinguishing factors may include the presence of depression, anxiety, or personality pathology (Maloney et al., 2009). High levels of opiate use are related to increased risk of suicide, not limited to intentional drug overdose (Ilgen et al., 2016). It has been estimated that 20–30 % of deaths by opioid overdose are best classified as suicides (Oquendo and Volkow, 2018). Prevention efforts depend on identifying which opiate users are at risk of dying by medical complications, accidental overdose, or suicide. Identifying a profile of risk for premature death in high-risk populations like opiate users may be difficult. There are some indications that accidental opiate overdoses and suicide by opiate overdose have been misclassified in recent epidemiologically-based research (Rockett et al., 2018). Epidemiological research can only offer clues about national level risk-factors for opioid-related mortality if medical examiners are able to correctly classify the manner of death in national death reporting surveillance systems. Research evaluating suicide decedents is limited (Ribeiro et al., 2018) and little is known about factors which differentiate individuals who die by suicide from those who die by accidental overdose. Clinical (Hakansson and Gerle, 2018) and forensic (Stone et al., 2017) psychologists have called for the use of psychological autopsy evaluations of premature deaths among opioid users. Post-mortem research has evaluated large, nationally or regionally representative databases containing information about decedents with opioid use disorders or opioid prescriptions. Differentiating accidental overdoses from suicide by overdose may be complicated in post-mortem research (Rockett et al., 2018) when information about suicidal intent is limited. Psychological autopsy methodologies may enhance population-wide analyses because they integrate autopsy reports, police death scene investigations, medical and psychiatric record review, and interviews with decedents’ family members. While psychological autopsy studies cannot account for decedents’ subjective experience, validated postmortem methodologies can be used to characterize decedents’ functioning prior to death and evaluate manner of death (Conner et al., 2011; Connor et al., 2012). By definition, suicidal intent differentiates deaths by intentional overdose from deaths by accidental overdose. Opioid use disorders and prescription opioid misuse are independently associated with an increased risk of suicidal ideation, planning, and attempts when adjusting for physical and mental health conditions (Ashrafioun et al., 2017). Suicidal intent may be a continuous, multi-faceted, or dynamic construct. Most subjects reported ambivalence about suicidal intent following an opioid overdose (Neale, 2000). Illicit drug use is significantly related to non-fatal suicide attempts but not suicidal ideation in multivariate analyses controlling for psychiatric diagnoses (Ashrafioun et al., 2015). Thus, it is possible that individuals who die by accidental and intentional overdose cannot be categorized based on evidence of suicidal ideation or suicidal intent prior to death. The primary aim of the present study was to extend the post-mortem opioid literature by using psychological autopsy research to compare opioid users who died by natural causes, accidents, and suicide. We compared subjects on characteristics which have been shown to increase risk of morbidity or mortality in nationally representative studies of decedents. Specifically, we evaluated between-group differences in demographic background, clinical and substance use characteristics, and treatment history. We also compared subjects’ experiences of negative life events leading up to death. This study assessed circumstances at the time of death which differentiate risk of death by accident, suicide, or natural causes among opiate users. We evaluated whether opioid users who died by suicide or accident showed differences in beliefs about death, preparation for life-threatening behaviors or death,
2. Materials and methods 2.1. Subjects Substance use and suicide risk were evaluated in 63 decedents with positive toxicology results for opiates at death. Subjects were collected from a broader IRB-approved research study looking at factors associated with completed suicide of individuals who died in Cuyahoga County, Ohio, during the years 1989–2017 (Overholser et al., 2012). A next-of-kin informant was recruited by the research team to be consented and interviewed concerning the deceased individual, and all available collateral information, such as medical examiner’s reports, police reports, legal records, medical/psychiatric records, were collected with a release of information from the next-of-kin. Next-of-kin included parents, spouses, siblings, extended family members, and friends, with the most common relationships being parent or spouse. In the current study, subjects were divided into three groups based on the Medical Examiner’s classification of death: adults dying by suicide (n = 19), accident (n = 19), and natural causes (n = 25). Of note, all but one accidental death (n = 18) died of an opiate overdose. 2.2. Measures The Structured Interview for DSM-IV (SCID) is a structured diagnostic assessment which was used to identify Axis I disorders among decedents (First et al., 1995). SCID items were adapted for psychological autopsy such that they referred to symptoms experienced by the study subjects and not the informants. In addition to informant reports, SCID items were rated based on psychiatric, medical, and legal records. SCID interviews provided detailed information about the duration and severity of major mental illness for the deceased. The SCID shows excellent psychometric properties in psychological autopsy research. High levels of agreement are observed between participant and informant report on the SCID (Kappa = 0.68, mean Kappa = 0.74, range = 0.65 – 0.87; (Schneider et al., 2004). Suicide attempters and family member informants show an excellent level of concordance on the SCID (Kappa = 1.0; (DeJong and Overholser, 2009). Inter-rater reliability is in the excellent range among proxy informants for suicide decedents and agematched controls (Kappa = 0.96–1.0; (Dumais et al., 2005). The Structured Interview for DSM-IV Personality Disorders (SIDPIV) is a semi-structured, valid and reliable diagnostic assessment used to identify DSM-IV Axis II disorders (Pfohl et al., 1997). The SIDP-IV was adapted for psychological autopsy such that items referred to decedents, collateral records supplemented interviews, and consensus diagnosis procedures were used. Standardized questions assessed the presence and severity of dysfunction in domains ranging from social relationships, unusual thinking patterns (e.g., paranoia), self-perception, emotionality, and impulsivity that last for at least five years prior to death. Unusual patterns of personality functioning, such as those exhibited during hospitalization or episodic mental illnesses (e.g., mania), were excluded. Items were rated on four-point Likert type scale with ratings 0 (not present) to 3 (strongly present: the behavior or 2
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characteristic was persistently present over 5 years and caused significant impairment in functioning or distress). The SIDP-IV domain scores can be aggregated to provide dimensional ratings of personality pathology (Pfohl et al., 1997). Psychometric analysis of SIDP-IV diagnosis based on proxy-report indicates that rates of concordance are in the good to excellent range when consensus diagnosis procedures are used (Bernstein et al., 1997). The Modified Life Experiences Scale (MLES) is an 11-item measure of potentially stressful life events experienced in the time proximal or distal to suicide or natural death. In the present study, the presence of ten categories of stressors within three months of death were assessed using the MLES. The measure was derived from the Life Experiences Survey (LES; (Sarason et al., 1978) which shows good to excellent rates of test-retest reliability (r = .64) over a 5- to 6-week interval. The MLES has been used successfully in psychological autopsy research (Fisher and Overholser, 2014; Overholser et al., 2012). The Suicide Intent Scale – Planning Subscale (SIS-P) is a 7-item measure of suicidal planning and preparation for death which was adapted from Beck’s Suicide Intent Scale (Beck et al., 1974). Scores can range from 0 to 14, with higher scores reflecting elevated levels of premeditation for death. The measure was used with all subjects in the present study (including subjects who died by accident and natural causes). The circumstances of death for all subjects were evaluated for higher or lower levels of planning or suicidal ideation at the time of death. An acceptable level of internal consistency (α = .76) was observed in the 7-item scale used here.
Table 1 Demographics and diagnostic characteristics of decedents with positive postmortem opiate toxicology results (N = 63).
2.3. Procedures
Participants who died by accident were more likely than other decedents to have a history of opiate use disorder (χ² (N = 63) = 7.81, p = .02; accident: 52.6 %; suicide: 15.8 %; natural: 20.0 %) and alcohol use disorder (χ² (N = 63) = 10.58, p = .005; accident: 84.2 %; suicide: 47.4 %; natural: 36.0 %). Perhaps as a result of the increased prevalence of prescription substance use disorders involving antidepressant medications, polysubstance use disorders were more common among subjects who died by accident (χ² (N = 62) = 6.04, p = .049; accident: 42.1 %; suicide: 15.8 %; natural: 12.0 %). Opiate users showed no differences in risk for nicotine use disorder (accident: 64.7 %; suicide: 61.1 %; natural: 52.0 %) and other substance use disorders were too infrequent to conduct meaningful analysis. Subjects who died by accident were significantly more likely to have a prior accidental opiate overdose than subjects who died by suicide or natural causes (χ² (N = 61) = 8.65, p = .01; Table 2). Compared to opiate users who died by other causes, opiate users who died by accident were significantly more likely to have illicit (vs. prescribed) forms of opiates in their postmortem toxicology (χ² (N = 57) = 7.07, p = .03). The three groups of opiate users showed no difference in their typical method of opiate use (pill or other form), and were similar in the age of onset of opiate use and the number of years using opiates. Subjects identified as using opiates who died by accident did not appear to show a different set of risk factors for opiate use compared to subjects who died by natural causes or suicide. Subjects who died by accident, suicide, and natural causes showed similar rates of serious medical problems including chronic pain conditions, medical conditions, and inpatient medical hospitalization in the six months before death. We observed similar rates of homelessness, legal issues, and incarceration within six months of death among the groups of opiate users, and similar rates of potentially protective factors against complications of opiate use including lifetime and recent inpatient psychiatric treatment, lifetime substance use treatment, and the use of drug replacement therapy. Subjects who died by accidental death were significantly more likely to experience the stress related to conflict with a family member when compared to opiate users who died by suicide or natural causes (χ² (N = 61) = 8.17, p = .02). We observed similar rates of conflict with parents, spouses, children, and friends between the groups of opiate users.
Age M (SD) Male gender White race Married > High school diploma Employed Major depression Bipolar disorder Anxiety disorder Posttraumatic stress disorder Psychotic disorder Any personality disorder
Suicidal Death (n = 19)
Accidental Death (n = 19)
Natural Cause Death (n = 25)
Test Statistic
p-value
50.26 (18.90) 73.70 94.70 42.10 42.10
42.42 (12.37) 84.20 94.70 26.30 31.60
50.68 (15.33) 48.00 88.00 56.00 48.00
1.76
.18
6.97* 0.94 3.89 1.21
.03 .63 .14 .55
31.60 63.20 0.00 10.50 10.50
52.60 21.10 5.30 15.80 10.50
36.00 40.00 4.00 12.00 4.00
2.39 6.98* 0.95 2.87 0.88
.30 .03 .62 .24 .64
0.00 31.60
5.30 52.60
4.00 28.00
0.95 3.76
.62 .15
M = Mean; SD = Standard deviation. Note: Data are reported as % unless otherwise specified. All test-statistics reported are chi-square values except for age with is reported as an F-value for ANOVA. * p-value < .05.
Psychological autopsy procedures evaluated cause of death, psychological diagnoses, and psychosocial characteristics. Written informed consent was obtained from legally-defined next-of-kin for informant-based retrospective diagnostic interviews. All assessment procedures followed the guidelines for psychological autopsy research (Hawton et al., 1998). Informant interviews were used to evaluate the presence, duration, and severity of psychological symptoms. Interviews were typically conducted approximately six months after the death of study subjects in order to reduce the effects of memory decay or possible risks of exacerbating bereavement (Connor et al., 2012). Interviews were supplemented by medical examiner’s reports, medical records, psychiatric records, and police reports. Collateral documentation was used to evaluate the reliability of information provided by informants and to support data collection. An extensive report detailing all of the information gathered during the interview session was created by a trained social worker. All records were reviewed by a board certified psychiatrist, a board certified clinical psychologist, a master's level social worker, and a neuroscientist to confirm item-level data and diagnoses. The consensus report was reviewed by each mental health professional prior to a review meeting (Ebert, 1987). 2.4. Data analysis The suicide, accidental death, and natural death groups were compared on several dependent measures, using chi-square to examine categorical variables and one-way analyses of variance (ANOVA) to examine continuous variables. 3. Results 3.1. Accidental deaths Men were significantly over-represented in the group of opiate users who died by accident than in other groups (χ² (N = 63) = 6.97, p = .03; Table 1). Opiate users who died by accident, suicide, and natural causes were similar in terms of age, race, marital status, educational attainment, and employment status at the time of death. 3
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Table 2 Substance use characteristics of decedents with positive post-mortem opiate toxicology results (N = 63).
Age of onset of opiate use M (SD) Duration of opiate use M (SD) Oral method of opiate use Chronic pain conditions Homelessness Incarceration Substance use treatment Use of drug replacement therapy Prior unintentional overdose Illicit opiates in post-mortem toxicology
Suicidal Death (n = 19)
Accidental Death (n = 19)
Natural Cause Death (n = 25)
Test Statistic
p-value
32.16 (21.38) 5.60 (5.75) 68.40 52.60 0.00 26.30 31.60 5.30 5.30 36.84
36.21 (13.48) 6.35 (8.04) 57.90 68.40 5.30 21.10 47.40 5.30 26.30 66.67
39.57 (15.73) 6.50 (9.92) 60.00 72.00 4.00 8.00 20.00 0.00 4.00 25.00
0.60 0.04 0.48 1.92 0.95 3.09 3.71 2.30 8.65* 7.07*
.55 .96 .79 .38 .62 .21 .16 .32 .01 .03
M = Mean; SD = Standard deviation. Note: Data are reported as % unless otherwise specified. All test-statistics reported are chi-square values except for age and duration which are reported as F-values for ANOVA. * p-value < .05.
3.2. Death by suicide
3.3. Sensitivity analysis
Opiate users who were suicide decedents were more likely than subjects that had accidental or natural deaths to have any depressive disorder (χ² (N = 63) = 10.66, p = .005), including major depressive disorder (χ² (N = 63) = 6.98, p = .03). The three groups of opiate users showed similar rates of bipolar disorder, anxiety disorders, posttraumatic stress disorder, psychotic disorders, and personality disorders. None of the three groups differed in having a history of non-fatal suicide attempts. However, suicide decedents had a higher number of prior suicide attempts than those who died by natural causes (F(2, 44) = 4.52, p = .02; Tukey HSD p = .02). Opiate users who died by accident experienced a similar number of non-fatal suicide attempts as opiate users who died by suicide and natural causes. Suicide decedents showed the highest average number of lifetime stressors compared to other opiate users who died by accident or natural causes (F(2, 57) = 4.33, p = .02). The number of stressors experienced by suicide decedents was significantly higher than those experienced by opiate users who died by natural causes (p = .01). Suicide decedents were significantly more likely to experience the end of a romantic relationship in the six months prior to death when compared to other groups (χ² (N = 61) = 6.97, p = .03). No differences were observed between the groups of opiate users in the rate of recent divorces or marital separations. Opiate users who died by suicide and accidents showed similarities in the rates at which they experienced most other stressors in the six months before death. No differences were observed in the rate at which subjects who died by suicide or accident experienced recent bereavement, financial problems, occupational difficulties or unemployment, or the hospitalization of family members. Opiate users who died by suicide showed higher levels of recent planning for death (SIS-P score; F(2, 57) = 43.43, p < .001) than individuals died by accidental or natural causes. Suicide decedents showed significantly higher levels of preparation for death than the other groups of opiate users in all areas including isolation at time of death (F(2, 53) = 7.45, p = .001), timing self-harm to increase the likelihood of death (F(2, 52) = 6.17, p = .004), taking precautions to prevent interruption during opiate use or suicide (F(2, 54) = 8.91, p < .001), taking final acts in anticipation of death F(2, 55) = 7.77, p = .001), or preparation for potentially lethal self-harm (F(2, 56) = 19.95, p < .001). Only suicide decedents vocalized thoughts of death (F (2, 58) = 12.77, p < .001) or completed suicide notes (F(2, 60) = 12.22, p < .001) in the time before death.
In order to clarify our original analyses, we conducted sensitivity analyses to determine if our initial results accurately described differences specifically between death by suicide and death by accidental opiate overdose among opiate users. Given our smaller number of subjects per group, we decided to execute this as a sensitivity analysis rather than the main results. For this analysis, we excluded data from opiate users who died by natural death (n = 25) and subjects who died by accidental causes other than accidental overdose (n = 1), only including opiate users who died by accidental causes if they died by overdose (n = 18). Finally, we repeated the analyses comparing opiate users who died by any form of suicide, including 5 subjects who died by opiate overdose (26.3 %). The findings provided further support to our central aim of comparing risk for morbidity and mortality among opiate users across different types of death and the corresponding results. The pattern of results which emerged from comparing accidental overdose deaths to suicides was remarkably similar to the analyses comparing opiate users who died by natural causes, accidents, and suicide. No demographic differences emerged between subjects who died by accidental overdose or suicide. The chi-square analysis which suggested that subjects who died by accidental overdose were more likely than suicide decedents to have polysubstance use disorders was reduced to a non-significant trend (χ² (N = 37) = 3.63, p = .06). No differences emerged in the number or kind of stressful life events in sensitivity analyses comparing subjects who died by accidental overdose and suicide. In the sensitivity analysis, differences were observed between the group of subjects who died by accidental opiate overdose and those who died by suicide in the average number of prior non-fatal suicide attempts in the sensitivity analysis. Subjects who died by suicide had a significantly higher number of non-fatal suicide attempts (M = .47, SD = .51) than subjects who died by accidental overdose (M = .09, SD = .30; F(1, 26) = 4.87, p = .04). No other comparisons differed from the results found in the main analyses. 4. Discussion The present results suggest that opiate users who die by suicide and by accident show separate, but partially overlapping risk profiles. Opiate users who die from preventable manners of death are different from opiate users who die by natural causes (i.e. those who receive prescription medication in hospital settings). Individuals with serious mental illness are at a heightened risk of death relating to purposeful and accidental overdose from opiate misuse. Individuals with serious mental illness are significantly more likely to experience opiate use disorders and to develop suicidal ideation in the context of co-occurring opiate-use and sedative-use disorders (Spivak et al., 2018). The present 4
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and their family member informants (DeJong and Overholser, 2009). With postmortem research, the cause of death is not always clear, and the medical examiner must rely on an integration of various sources of information when determining cause of death (Byard, 2008). With the current increase in deaths related to opioid overdose, it can become challenging to decide if a person died by intentional or accidental causes. A recent study (Liu et al., 2019) found that mathematical models can help to provide more accurate estimates of international overdose, especially when suicide rates have been underreported. However, a thorough evaluation conducted by a qualified medical examiner integrates many sources of information to make the final determination (Gill et al., 2013). Furthermore, forensic examiners are quite accurate even without conducting an autopsy, and cause of death rulings can be trusted when based on a thorough forensic autopsy examination (Nashelsky and Lawrence, 2003). There is limited research comparing death type among opiate users, and the present findings are limited by small samples collected postmortem. Few available models predict risk for suicide among opiate users, much less the specific form of premature death in high-risk groups. Many opioid users experience both non-fatal suicide attempts and truly accidental overdoses (Rossow and Lauritzen, 1999). Risk factors for accidental overdose and non-fatal suicide attempts may also overlap (Bohnert et al., 2010). Opioid users who experience non-fatal overdoses and non-fatal suicide attempts may represent a complex population at risk of fatal outcomes. Research with populations who have experienced opioid related morbidity may provide insight into cognitive and affective risk factors for fatal outcomes. The current results help to identify potential targets for assessment among opiate users. In the current opiate crisis, it is imperative that clinicians understand the nuances of potential overdose and how accidental behaviors can be distinguished from purposeful ones. Opiate users overall are at high suicide risk. Although a history of suicidal behavior is common between individuals who die accidentally and those who die by suicide, there is an important distinction in the degree of planning for death. Early intervention may focus on awareness of suicidal planning, addressing the relevant psychopathology, and targeting ongoing life stress. It may be possible to reduce the risk of death by understanding what factors lead some opiate users toward a suicidal crisis.
results show that as compared to cases of natural death, opiate users who die by accident were significantly more likely to be male and to have a history of opiate, alcohol, or polysubstance use disorder. Thus, adults who die by accidental death show stronger patterns of substance abuse than found in opiate users who die by suicide. Higher levels of alcohol use are associated with higher risk for suicide attempt (Borges et al., 2016). When combined with other drugs, alcohol creates a synergistic risk for suicide attempts (Bagge and Borges, 2017) and death by suicide (Kõlves et al., 2017). In the present study, opioid users who died by accident had higher rates of alcohol use disorder (84.2 %) and alcohol in their system in their toxicology at autopsy (42.1 %) as compared to opiate users who died from suicide (alcohol use disorder = 47.4 %; alcohol toxicology = 26.3 %). The use and abuse of alcohol can play a role in a broad spectrum of causes of death. Acute intoxication can be used to facilitate a suicide attempt (Bagge et al., 2015), perhaps by lowering a person's inhibitions and impairing rational thinking, potentially resulting in impulsive and dangerous acts. The risk of suicidal behavior is increased in proportion to the amount of alcohol consumed during the previous 6 h (Borges et al., 2016). Future research may begin to disaggregate the influence of acute and chronic substance use on intentional and unintentional causes of death. In the present study, opiate users who died by accidental causes were more likely to have a prior accidental overdose, to have opiates in their blood at time of death, and to experience conflict with an extended family member. In comparison, opiate users who died by suicide were more likely to meet criteria for any depressive disorder, a major depressive disorder, and to have experienced a higher number of lifetime stressors. These suicidal individuals also showed more planning and preparation for death than the other two groups. Number of prior suicide attempts was similar between individuals in the accidental and suicide death groups, while those who died by suicide had a higher number of previous attempts compared to those who died by natural causes. Overall, accidental overdose and suicide in opiate users presented separate categories of high-risk behaviors sharing common vulnerabilities while both differed from opiate users who died by natural causes. Substance users die at a younger age than the general population, especially when the cause of death is suicide or accident (Stenbacka et al., 2010). Opiate users may be vulnerable to various forms of premature death (Case and Deaton, 2015), especially when they are not involved with treatment (Peles et al., 2013). Suicidal planning at the time of death, but not a prior suicide attempt, may be related to risk for suicide. In contrast, a history of opiate overdose may be related to risk of accidental death among opiate users. Acute stressors and prior nonfatal suicide attempts are common among high-risk groups and may not be specific enough to distinguish risk. Accidental deaths in opiate users seem to follow repeated, non-fatal overdose as well as other high-risk substance use behaviors. In contrast, suicide deaths in opiate users seem to occur in the context of depression. In prior research, a history of non-fatal suicide attempts did not differentiate risk of suicide from risk of accidental overdose (Ribeiro et al., 2016). However, the suicide decedents in our sample showed higher levels of planning for death than individuals who had accidental and natural deaths. The current study had several of limitations. Stressful life events were rated for their categorical presence or absence. The timing (Bagge et al., 2013) and magnitude (Buchman-Schmitt et al., 2017) of stressful life events can affect suicide risk (Bagge et al., 2013). Furthermore, because of the nature of psychological autopsy research, the present study was unable to evaluate the subjective impact of negative life events. However, postmortem research often includes access to information that is not readily available in self-report surveys, including family views, medical records, suicide notes, police records, and toxicology results. Furthermore, prior research has found a high level of agreement on diagnostic questions posed to suicidal psychiatric patients
Role of funding source Nothing declared. Declaration of Competing Interest No conflict declared. Contributors Alison J. Athey, M.A. declares that she materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Eleanor E. Beale, B.A. declares that she materially participated in the data analysis and article preparation for the current manuscript and has approved the final article. James C. Overholser, Ph.D. declares that he materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Craig A. Stockmeier, Ph.D. declares that he materially participated in the research, data analysis, and article preparation for the current manuscript and has approved the final article. Courtney L. Bagge, Ph.D. declares that she materially participated in the data analysis and article preparation for the current manuscript and has approved the final article. 5
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