In the United States in 2017, more than 47,000 people died by suicide and more than 70,000 people died by drug overdose.1,2 These dual epidemics are a growing public health crisis, contributing to recent decreases in life expectancy.2 Furthermore, these epidemics are not unrelated. Substance use and substance use disorders (SUD) are significant risk factors for suicidal thoughts and behaviors. In this article, we provide an overview of the literature on suicidal thoughts and behaviors in people with SUD, identify putative mechanisms underlying this association, and discuss models for prevention of suicide-related fatalities.
Prevalence and Elevated Risk of Suicide Associated with Substance Use
Studies using multiple methods (eg, cohort studies, longitudinal studies, psychological autopsies, nationally representative surveys) consistently demonstrate that the use of substances and presence of SUD are among the most robust predictors of suicidal thoughts and behaviors.3–5 Acute substance intoxication is common in people who attempt and who die by suicide. A meta-analysis of studies of alcohol use and suicide attempts found that acute use of alcohol was associated with nearly 7 times higher odds of suicide attempt, and “high levels” of alcohol use were associated with more than than 37 times higher odds.6 Consistent with these findings, in a large nationally representative survey, alcohol was detected in approximately one-third of people who died by suicide.7
The misuse of substances and SUD are also robustly associated with suicidal behavior. A review of psychological autopsy studies found that between 19% and 63% of people who died by suicide had an SUD.8 A review of cohort studies found that death by suicide was 10 times more common in alcohol use disorder than would be expected based on demographic variables, and 13 times more common in people with opioid use disorder.4 This association remains significant even above and beyond the contribution of other co-occurring psychiatric disorders.5
Although these statistics clearly demonstrate the elevated risk for suicidal thoughts and behaviors in people with SUD, these are likely underestimates of suicide in this population. The classification of deaths as suicide typically relies on corroboration (eg, suicide note, psychiatric diagnosis), which is often not available.9 Accordingly, many substance overdose deaths categorized as ”unintentional” or “undetermined” may in fact be suicides, obscuring the impact of suicidal thinking and intent on substance-related overdose. Indeed, this dichotomous categorization of overdose events as either suicidal or accidental fails to take into account the continuum of suicidal motivation and intent that may contribute to overdose events and other risky or life-threatening behaviors.10 Consider a person without any desire to die, who has never engaged in suicide planning, and has no conscious intention of using substances in a manner that would lead to death. Such a person may have a potentially lethal SUD such as injection opioid use disorder, and may be cognizant that repeated injection use could result in earlier death, but the pattern of repeated use follows addiction drives and not suicidal motivations, (ie, “hoping to get high and not to die”). In the event of drug overdose, the most probable manner of death categorization would be that the person experienced an unintentional overdose. At the other end of the spectrum, a person experiencing ongoing desire to die and episodic suicide planning or intentions would be at much greater risk for a drug overdose event that was significantly influenced by suicidal motivations and intentions. This would be categorized as a suicide if the person left any suicidal communications prior to the overdose but might be categorized as undetermined or even unintentional in the absence of such evidence (ie, a “missed” suicide). Between these ends of the spectrum, people may also experience variable combinations of desire to die (infrequent episodes to frequent episodes, brief or sustained duration of death wish, low to high intensity of death wish) and suicidal intentionality (no conscious intention to episodes of fully conscious intention). Research aimed at better identifying such subgroups based on suicidal cognitions and other risk factors, the stability of these groups over time, and their implications for outcomes (eg, nonfatal or fatal overdose, suicide attempt) is needed to inform better detection and prevention of risks.
The strength of the association between SUD and suicide is contingent upon a variety of factors. People entering treatment with severe addiction profiles tend to have more severe suicidal thoughts and behaviors compared to those presenting with mild to moderate SUD.11 The prevalence of suicidal thoughts and behaviors also varies based on substance type. Central nervous system (CNS) depressants such as alcohol, opioids, and sedatives have been strongly linked to suicidal thoughts and behaviors. Alcohol use disorder is associated with elevated risk for suicidal behavior, especially when consumed in combination with another substance.3,11 Particularly heightened risk has also been noted in sedative and opioid use disorder.4,12 For example, a large study of treatment-seekers with opioid use disorder found that 42% had a history of suicide attempt.13 Suicidal behavior is also common in people with stimulant use disorder, although possibly to a lesser extent.12 The literature on cannabis and suicidal thoughts and behaviors has yielded somewhat mixed results; however, chronic cannabis use appears to be associated with heightened suicidal thoughts and behaviors.12,14,15
Notably, suicidal thoughts and behaviors appear to be more common in women with SUD.4,12 Women exhibit a higher prevalence of suicidal thoughts and behaviors and women with drug use disorders (SUD not including alcohol or tobacco) have a particularly heightened risk of suicide mortality.4,11 Controlling for psychiatric illness, which tends to be more common in women than men with SUD, mitigates this effect.12 Sex differences remain under-studied and an important area for future research.4
Potential Mechanisms Explaining Substance Use Association with Elevated Risk for Suicide
The contributions of substance use to a person's suicide risk profile may be considered from multiple perspectives, including (1) the neurobiological effects of both acute intoxication and chronic substance exposure, (2) sociocultural risk factors associated with SUD, (3) health-related risk factors associated with SUD, and (4) overlapping genetic predisposition for suicide and SUD.
Neurobiological Suicide Risk Factors Associated with Acute Intoxication and SUD
Acute substance intoxication may amplify suicidal cognitions in several ways. Alcohol and sedative-hypnotics disinhibit executive functioning, resulting in loss of cognitive control over self-injurious thoughts and enhanced risk that thoughts will transition to behavior (ie, increased impulsivity). Stimulant intoxication is associated with heightened impulsivity and aggression, which may affect both transition from suicidal ideation to attempt as well as the relative lethality of means selected for suicide attempt. Opioid intoxication has inherent mortality risk due to lethality associated with respiratory depression, and it also confers risk via social disconnection, which is a hallmark of opioid intoxication. Hallucinogens and substances that induce acute psychosis may alter cognitive reasoning in ways that enhance self-harm risk, such as induction of paranoid ideation and other persecutory perceptions influencing motivation for immediate escape.
SUD is neurobiologically associated with allostatic changes in reward and stress circuitry,16,17 rendering significant increases in stress sensitivity and distress intolerance, irritability, dysphoria, anxiety, and insomnia, all of which elevate proximal suicide risk.
Sociocultural Suicide Risk Factors Associated with SUD
The number of adverse childhood events (ACE) has been strongly and positively associated with substance use initiation and lifetime risk for development of alcohol and drug use disorders,18 and with attempted suicide throughout the developmental life span.19 Furthermore, the strength of the relationship between ACE and suicide attempt is reduced when adjusting for alcohol and drug use, suggesting that substance use could be a partial mediator of the relationship between childhood trauma and suicide attempts.
In the United States, poverty, low educational attainment, unemployment, and rural housing have all been associated with increased mortality due to suicide and substance poisoning (termed “deaths of despair,” by economists Anne Case and Sir Angus Deaton in their 2015 report20 on increasing morbidity and mortality related to suicide and substance use among US middle-aged, non-Hispanic whites), and further investigations suggest that erosion of social networks important to resilience and valuation of life, such as religious institutions, community gathering spaces, and readily available health care, are also contributing to increasing substance-related problems and suicide.21
Health-Related Suicide Risk Factors Associated with SUD
Chronic pain is common among those with SUD and represents a significant risk factor for both suicide and opioid overdose.22 Some of the causes of chronic pain in those with SUD include contraction of infectious diseases, substance-related injury, and domestic violence. These latter conditions may also contribute significantly to physical disability, social isolation, and hopelessness, all of which are independent risk factors for suicide.
Genetic Risk Factors Associated with SUD
SUD genetic epidemiology has revealed the polygenic structure of SUD (multiple genetic determinants contributing cumulatively to the risk for and maintenance of SUD), with many neurotransmitter system genes involved, particularly genes affecting dopaminergic functioning.23 Genetic risk factors for suicide include dysregulation of stress responses mediated through the hypothalamic-pituitary-adrenal axis,24 which has also been studied as a factor influencing development of SUD as well as relapse risk for SUD in people in early abstinence.17 Although not yet identified, overlapping genetic determinants may provide a causal link in the association between SUD and suicide risk.
Suicide Prevention in Persons with SUD
Health Care Delivery and Screening Gaps
Despite robust data supporting the feasibility and effectiveness of universal suicide risk screening, many health care settings have not yet successfully implemented systematic screening and response algorithms. Recent analyses demonstrate that brief, evidence-based, universal screening and prevention interventions in emergency department settings are cost-effective and reduce future suicide attempts and deaths in at-risk adults.25 Reviews of effective algorithms for suicide risk reduction in pediatric emergency settings and hospital settings note that patients presenting with intoxication are frequently under-screened for suicide risk.26,27 Training the health care workforce to identify SUD as an independent and modifiable suicide risk factor, and to provide linkage to care for both SUD treatment and suicide risk reduction, will be a necessary strategy toward closing these gaps. In outpatient care settings (both primary care and specialized behavioral health care), suicide prevention optimization is largely being developed through data informatics analyses, such as machine learning applications to electronic health records and the incorporation of real-time technological symptom surveillance added to treatment as usual, both of which are superior to outpatient universal suicide-risk screening alone.28,29
Engaging those with SUD into SUD-specific, evidence-based treatment is effective for future suicide risk reduction.30 Medications to treat SUD play an important role in suicide prevention in two ways: (1) the effective reduction of substance use and relapse episodes, with consequential improvements in lifestyle and health risk factors, and (2) some medications may have direct pharmacological suicide prevention effects. For example, the mu opioid partial agonist/kappa opioid antagonist, buprenorphine, used to treat opioid use disorder, has demonstrated acute and enduring efficacy in reducing suicidality in patients with treatment-resistant depression.31 The anti-suicidal properties of ketamine in patients with depression is attenuated by the opioid antagonist, naltrexone, suggesting that opioid activation is a necessary component of ketamine's anti-suicidal mechanism.32 A large population health study of people treated with medications for alcohol use disorder and for opioid use disorder indicated that methadone treatment of opioid use disorder demonstrated the greatest anti-suicidal effect in this population, although active treatment with any medication was also associated with suicide reduction.33
The growing acknowledgement of the need for targeted suicide prevention in people with SUD has resulted in the recent development of psychosocial treatments for this population. Preventing Addiction Related Suicide (PARS)34 is a brief, group intervention designed to be implemented within SUD treatment and settings. PARS incorporates components of suicide prevention interventions, such as teaching about risk and protective factors, helping people to identifying warning signs, and provision of crisis resources. Preliminary data support the feasibility of PARS and show significant improvement in knowledge about suicide and increases in help-seeking behavior.34 PARS is intended as a secondary prevention strategy, which may be relevant to anyone with SUD.
Another treatment uses a tertiary prevention approach targeting adolescents with alcohol use disorder and suicidality. This intervention uses cognitive-behavioral therapy components drawn from treatments for suicidality and alcohol use disorder.35 This skills-based treatment includes standard cognitive-behavioral strategies (eg, problem solving, cognitive restructuring) applied specifically to the co-occurrence of these conditions. This treatment was designed to be delivered on an individual basis, weekly in the first 6 months then stepping down to biweekly for 3 months, and then monthly for an additional 3 months. In a small pilot, the treatment demonstrated initial feasibility and reduction in suicidal ideation.35
Persons with substance misuse and SUD are at significantly elevated risk for deaths influenced by suicidal motivations and intentions. Evidence-based treatments for SUD effectively reduce substance-related suicide risk as well as reduce other substance-related mortality risk. A substantial portion of those with SUD remain at elevated risk for suicide even when the SUD has been stabilized, and the frequency of SUD relapse during treatment further complicates enduring suicide risk in the SUD population. Thus, the evidence supports an approach to SUD care that includes suicide prevention education and universal suicide screening, as well as targeted treatment to reduce suicidal cognitions and behaviors in those identified as higher risk.
- Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and opioid-involved overdose deaths–United States, 2013–2017. MMWR Morb Mortal Wkly Rep. 2018;67(5152):1419–1427. doi:10.15585/mmwr.mm675152e1 [CrossRef] PMID:30605448
- Kochanek KD, Murphy SL, Xu JQ, Arias E. Deaths: final data for 2017. National Vital Statistics Report; vol 68 no 9. Hyattsville, MD: National Center for Health Statistics; 2019.
- Darvishi N, Farhadi M, Haghtalab T, Poorolajal J. Alcohol-related risk of suicidal ideation, suicide attempt, and completed suicide: a meta-analysis. PLoS One. 2015;10(5):e0126870. doi:10.1371/journal.pone.0126870 [CrossRef] PMID:25993344
- Wilcox HC, Conner KR, Caine ED. Association of alcohol and drug use disorders and completed suicide: an empirical review of cohort studies. Drug Alcohol Depend. 2004;76(suppl):S11–S19. doi:10.1016/j.drugalcdep.2004.08.003 [CrossRef] PMID:15555812
- Yuodelis-Flores C, Ries RK. Addiction and suicide: a review. Am J Addict. 2015;24(2):98–104. doi:10.1111/ajad.12185 [CrossRef] PMID:25644860
- Borges G, Bagge CL, Cherpitel CJ, Conner KR, Orozco R, Rossow I. A meta-analysis of acute use of alcohol and the risk of suicide attempt. Psychol Med. 2017;47(5):949–957. doi:10.1017/S0033291716002841 [CrossRef] PMID:27928972
- Conner KR, Huguet N, Caetano R, et al. Acute use of alcohol and methods of suicide in a US national sample. Am J Public Health. 2014;104(1):171–178. doi:10.2105/AJPH.2013.301352 [CrossRef] PMID:23678938
- Schneider B. Substance use disorders and risk for completed suicide. Arch Suicide Res. 2009;13(4):303–316. doi:10.1080/13811110903263191 [CrossRef] PMID:19813108
- Rockett IRH, Caine ED, Connery HS, et al. Discerning suicide in drug intoxication deaths: paucity and primacy of suicide notes and psychiatric history. PLoS One. 2018;13(1):e0190200. doi:10.1371/journal.pone.0190200 [CrossRef] PMID:29320540
- Connery HS, Taghian N, Kim J, et al. Suicidal motivations reported by opioid overdose survivors: a cross-sectional study of adults with opioid use disorder. Drug Alcohol Depend. 2019;205:107612. doi:10.1016/j.drugalcdep.2019.107612 [CrossRef] PMID:31627077
- Simoneau H, Ménard JM, Blanchette-Martin N. Addiction severity and suicidal behaviors among persons entering treatment. Arch Suicide Res. 2017;21(2):341–353. doi:10.1080/13811118.2016.1182093 [CrossRef] PMID:27135975
- Bohnert KM, Ilgen MA, Louzon S, McCarthy JF, Katz IR. Substance use disorders and the risk of suicide mortality among men and women in the US Veterans Health Administration. Addiction. 2017;112(7):1193–1201. doi:10.1111/add.13774 [CrossRef] PMID:28301070
- Darke S, Ross J, Marel C, et al. Patterns and correlates of attempted suicide amongst heroin users: 11-year follow-up of the Australian treatment outcome study cohort. Psychiatry Res. 2015;227(2–3):166–170. doi:10.1016/j.psychres.2015.04.010 [CrossRef] PMID:25908265
- Delforterie MJ, Lynskey MT, Huizink AC, et al. The relationship between cannabis involvement and suicidal thoughts and behaviors. Drug Alcohol Depend. 2015;150:98–104. doi:10.1016/j.drugalcdep.2015.02.019 [CrossRef] PMID:25772435
- Borges G, Bagge CL, Orozco R. A literature review and meta-analyses of cannabis use and suicidality. J Affect Disord. 2016;195:63–74. doi:10.1016/j.jad.2016.02.007 [CrossRef] PMID:26872332
- Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35(1):217–238. doi:10.1038/npp.2009.110 [CrossRef] PMID:19710631
- Wemm SE, Sinha R. Drug-induced stress responses and addiction risk and relapse. Neurobiol Stress. 2019;10:100148. doi:10.1016/j.ynstr.2019.100148 [CrossRef] PMID:30937354
- Dube SR, Felitti VJ, Dong M, Chapman DP, Giles WH, Anda RF. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. Pediatrics. 2003;111(3):564–572. doi:10.1542/peds.111.3.564 [CrossRef] PMID:12612237
- Dube SR, Anda RF, Felitti VJ, Chapman DP, Williamson DF, Giles WH. Childhood abuse, household dysfunction, and the risk of attempted suicide throughout the life span: findings from the Adverse Childhood Experiences Study. JAMA. 2001;286(24):3089–3096. doi:10.1001/jama.286.24.3089 [CrossRef] PMID:11754674
- Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci USA. 2015;112(49):15078–15083. doi:10.1073/pnas.1518393112 [CrossRef] PMID:26575631
- Scutchfield FD, Keck CW. Deaths of despair: why? What to do?Am J Public Health. 2017;107(10):1564–1565. doi:10.2105/AJPH.2017.303992 [CrossRef] PMID:28902554
- Petrosky E, Harpaz R, Fowler KA, et al. Chronic pain among suicide decedents, 2003 to 2014: findings from the National Violent Death Reporting System. Ann Intern Med. 2018;169(7):448–455. doi:10.7326/M18-0830 [CrossRef] PMID:30208405
- Prom-Wormley EC, Ebejer J, Dick DM, Bowers MS. The genetic epidemiology of substance use disorder: a review. Drug Alcohol Depend. 2017;180:241–259. doi:10.1016/j.drugalcdep.2017.06.040 [CrossRef] PMID:28938182
- Oquendo MA, Sullivan GM, Sudol K, et al. Toward a biosignature for suicide. Am J Psychiatry. 2014;171(12):1259–1277. doi:10.1176/appi.ajp.2014.14020194 [CrossRef] PMID:25263730
- Dunlap LJ, Orme S, Zarkin GA, et al. Screening and intervention for suicide prevention: a cost-effectiveness analysis of the ED-SAFE interventions [published online ahead of print August 27, 2019]. Psychiatr Serv. doi:10.1176/appi.ps.201800445 [CrossRef]
- Brahmbhatt K, Kurtz BP, Afzal KI, et al. PaCC Workgroup. Suicide risk screening in pediatric hospitals: clinical pathways to address a global health crisis. Psychosomatics. 2019;60(1):1–9. doi:10.1016/j.psym.2018.09.003 [CrossRef] PMID:30384966
- Kleiman EM, Nock MK. New directions for improving the prediction, prevention, and treatment of suicidal thoughts and behaviors among hospital patients [published online ahead of print June 13, 2019]. Gen Hosp Psychiatry. doi:10.1016/j.genhosppsych.2019.06.002 [CrossRef] PMID:31229288
- Simon GE, Johnson E, Lawrence JM, et al. Predicting suicide attempts and suicide deaths following outpatient visits using electronic health records. Am J Psychiatry. 2018;175(10):951–960. doi:10.1176/appi.ajp.2018.17101167 [CrossRef] PMID:29792051
- Whiteside U, Richards J, Huh D, et al. Development and evaluation of a web-based resource for suicidal thoughts: NowMattersNow.org. J Med Internet Res. 2019;21(5):e13183. doi:10.2196/13183 [CrossRef] PMID:31045498
- Ilgen MA, Harris AH, Moos RH, Tiet QQ. Predictors of a suicide attempt one year after entry into substance use disorder treatment. Alcohol Clin Exp Res. 2007;31(4):635–642. doi:10.1111/j.1530-0277.2007.00348.x [CrossRef] PMID:17374043
- Thase ME, Stanford AD, Memisoglu A, et al. Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder. Neuropsychopharmacology. 2019;44(13):2268–2276. doi:10.1038/s41386-019-0451-3 [CrossRef] PMID:31254971
- Williams NR, Heifets BD, Bentzley BS, et al. Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Mol Psychiatry. 2019;24(12):1779–1786. doi:10.1038/s41380-019-0503-4 [CrossRef] PMID:31467392
- Molero Y, Zetterqvist J, Binswanger IA, Hellner C, Larsson H, Fazel S. Medications for alcohol and opioid use disorders and risk of suicidal behavior, accidental overdoses, and crime. Am J Psychiatry. 2018;175(10):970–978. doi:10.1176/appi.ajp.2018.17101112 [CrossRef] PMID:30068260
- Voss WD, Kaufman E, O'Connor SS, Comtois KA, Conner KR, Ries RK. Preventing addiction related suicide: a pilot study. J Subst Abuse Treat. 2013;44(5):565–569. doi:10.1016/j.jsat.2012.10.006 [CrossRef] PMID:23375569
- Esposito-Smythers C, Spirito A, Uth R, LaChance H. Cognitive behavioral treatment for suicidal alcohol abusing adolescents: development and pilot testing. Am J Addict. 2006;15(s1)(suppl 1):126–130. doi:10.1080/10550490601006188 [CrossRef] PMID:17182428