Am J Psychiatry 169:1, January 2012 ages 40 to 49 have the highest rates of accidental overdose. (4). Analyses of overdose decedents in West Virginia sug-.
A r t ic le
R isk o f D e a th Fro m A c c id e n ta l O v e rd o se A sso c ia te d W ith P sy c h ia tric a n d S u b sta n c e U se D iso rd e rs Amy S.B. Bohnert, Ph.D.
O b je c tiv e : D espite dram atic increases in the rate of fatal accidental overdose in recent years, risk factors for this outcom e rem ain poorly understood, particularly in clinical populations. The authors exam ined the association of psychiatric and substance use diagnoses w ith death from accidental overdose.
Mark A. Ilgen, Ph.D. Rosalinda V. Ignacio, M.S. John F. McCarthy, Ph.D.
M e th o d : The study follow ed a cohort of patients from 2000 to 2006. The cohort included all patients treated in Veterans Health Adm inistration facilities during fiscal year 1999 w ho w ere alive at the start of fiscal year 2000 (N=3,291,891). D eath by accidental overdose w as determ ined using National D eath Index records and defined as a death w ith underlying cause of death coded to ICD -10 codes X40–X45 (N=4,485). D iagnoses w ere determ ined by patient m edical records.
Marcia Valenstein, M.D. Frederic C. Blow, Ph.D.
R e s u lts : Adjusting for dem ographic and clinical characteristics, hazard ratios of death by accidental overdose associated
w ith prior psychiatric and substance use disorder diagnoses ranged from 1.8 to 8.8. Significant associations of non-substancerelated psychiatric disorders w ith risk of death by accidental overdose persisted after additional adjustm ent for substance use disorders (hazard ratios from 1.2 to 1.8). D epressive disorders and anxiety disorders other than posttraum atic stress disorder had stronger associations w ith risk of m edication-related overdose death (hazard ratios, 3.02 and 3.07, respectively) than w ith risk of overdose death related to alcohol or ille gal drugs (hazard ratios, 1.89 and 1.23, respectively). C o n c lu s io n s : Am ong patients receiving care from the Veterans Health Adm inistration, death from accidental overdose w as found to be associated w ith psychiatric and substance use disorders. The study findings suggest the im portance of risk assessm ent and overdose prevention for vulnerable clinical subpopulations. (A m J P sy c h ia try 2 0 1 2 ; 1 6 9 :6 4 –7 0 )
D
eath from accidental overdose—unintentional death resulting from poisoning by illegal drugs, alcohol, or medications—is the second most common cause of accidental death in the United States (1). The rate of fatal unintentional overdose or poisoning among adults over age 18 increased by 124% between 1999 and 2007 (1). This increase is attributed largely to prescription drug overdoses, and particularly to overdoses related to opioid pain medication (2, 3). Given the importance of health systems to the distribution of prescription drugs that carry overdose potential and the treatment of individuals at risk for overdose, it is crucial to identify at-risk groups in clinical populations for targeted interventions. Little research has been conducted on risk factors for fatal accidental overdose, in clinical or other settings. Much of the available data come from surveillance systems (such as those implemented by the Centers for Disease Control and Prevention [CDC]), which have limited data on the characteristics of individuals who died from overdose. Previous analyses of these data indicate that men are more likely to die by accidental overdose, and individuals
ages 40 to 49 have the highest rates of accidental overdose (4). Analyses of overdose decedents in West Virginia suggest that substance abuse and mental illness may be common among those who die of an overdose (5, 6), although the lack of a comparison group did not allow the determination of whether the prevalences of these characteristics are significantly elevated. More detailed information regarding risk for nonfatal overdose has come from survey-based studies of chronic users of illegal drugs. These studies typically have samples from treatment settings and are often limited to one geographical region. Analyses suggest that individuals who meet criteria for substance use disorders (7–10) and individuals experiencing psychological distress (10, 11) have an elevated risk of nonfatal accidental overdoses compared with individuals without these conditions. Although understanding risk factors for accidental overdose among chronic drug users is important, questions regarding risk for accidental overdose in broader clinical populations remain unanswered. The purpose of this study was to examine the risk of accidental overdose
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B o h n er t, Ilg e n , Ig n acio , e t a l .
associated with substance use disorders and other psychiatric disorders among the entire population of patients who used Veterans Health Administration services within a single year. We examined clinical and mortality data to assess possible associations between specific psychiatric diagnoses and patients’ risks of accidental overdose death over a 7-year observation period. Because individuals with psychiatric conditions are more likely to have substance use disorders as well, we also examined the degree to which associations between psychiatric disorders and accidental overdose risk may be accounted for by comorbid substance use disorders. Additionally, we examined the association of psychiatric disorders with medicationrelated and alcohol- or illegal drug-related overdoses separately because of the different clinical implications for these two outcomes.
M e th o d S tu d y P o p u la tio n The study cohort included all patients who used Veterans Health Administration services in fiscal year 1999 (October 1, 1998–September 30, 1999) and were alive at the start of fiscal year 2000 (October 1, 1999). The sample, which comprised 3,291,891 individuals, has been described elsewhere (12). These individuals were followed until the end of fiscal year 2006 or death, whichever came first. The study was approved by the Ann Arbor Veterans Affairs Human Subjects Committee. Informed consent was waived by the Human Subjects Committee; all data were collected through the course of normal medical care and government mortality monitoring systems.
D a ta S o u rc e s The Department of Veterans Affairs (VA) National Patient Care Database was used to identify all individuals who had Veterans Health Administration inpatient, residential, or outpatient encounters in fiscal year 1999. The National Patient Care Database includes demographic and diagnostic information for all treatment contacts of patients seen anywhere in the national Veterans Health Administration health system. Information about vital status and cause of death from the start of fiscal year 2000 though the end of fiscal year 2006 were obtained from the CDC’s National Death Index. The National Death Index compiles death record data for all U.S. residents from state vital statistics offices. Among all available population-level sources of mortality data, the National Death Index has the greatest sensitivity in determining vital status (13). National Death Index searches were conducted for all individuals who used Veterans Health Administration services in fiscal year 1999 and did not have any record of Veterans Health Administration service use in fiscal years 2007 or 2008; searches were not conducted for individuals who used Veterans Health Administration services in fiscal years 2007 or 2008 given that they were known to be alive after the end of the observation period. In instances where the National Death Index search yielded multiple records as potential matches, procedures described previously by Sohn and colleagues (14) were used to ascertain “true” matches.
M e a su re s D e m o g r a p h ic c h a r a c te r is tic s . The available data allowed for examination of age and gender. Age was divided into 10-year categories to allow comparability of findings with prior research on suicide in the Veterans Health Administration (12, 15) and
A m J Psych ia try 1 6 9 :1 , Ja nu a ry 2 0 1 2
national overdose trends (1). VA priority status, which has eight categories and is based on factors such as income, presence of disabilities related to military service and other disabilities, and service-related factors (e.g., service in specific conflicts), was used to partially adjust for socioeconomic status (see the description at www.va.gov/healtheligibility/eligibility/PriorityGroupsAll.asp). Reliable information on other demographic characteristics was not available from patient records. D ia g n o s tic c h a r a c te r is tic s . All psychiatric diagnoses were based on ICD-9-CM diagnostic codes recorded during a visit in fiscal year 1998 or 1999. The psychiatric diagnoses examined were depression (major depressive disorder and non-major depressive disorder depression), schizophrenia (including schizoaffective disorder), bipolar I or II disorder, substance use disorders, posttraumatic stress disorder (PTSD), and other (non-PTSD) anxiety disorders. Diagnosis indicators were not mutually exclusive. Specific substance use disorders (opioid, stimulant [cocaine and amphetamines], cannabis, and other) were also included. Medical comorbidity was measured using the Charlson comorbidity score (16), a weighted index used to classify comorbid conditions that has been used to identify risk of mortality. A categorical variable was created for the Charlson score with the values of either 0 or 1, where 1 indicates ≥1 (17). O u tc o m e m e a s u re s . We obtained dates and causes of death from the National Death Index. Accidental overdose deaths were identified using ICD-10 underlying cause of death codes X40–X45, which include all poisoning deaths that were the result of ingestion of medications, alcohol, or illegal drugs. From National Death Index records, we additionally used ICD-10 T-codes, which describe the specific substance(s) that caused poisoning (as determined by the medical examiner) in order to create two additional outcome measures: 1) accidental overdose deaths due in part or in whole to prescription or over-the-counter medications (codes T360–T399, T402–T404, and T420–T509), henceforth called “medication-related overdoses,” and 2) accidental overdose deaths due in part or in whole to alcohol or to substances without widespread medical application in the United States (T400–T401, T405, and T407–T409), henceforth called “alcohol/ illegal drug-related overdoses.”
S ta tistic a l A n a ly sis We estimated a series of Cox proportional hazards regression models (18) to yield unadjusted hazard ratios to estimate risk of accidental overdose death for each variable of interest and the 95% confidence interval (CI) for each estimate. If the 95% CIs of hazard ratios associated with two different related tests do not overlap, then the hazard ratio associated with one condition is necessarily significantly larger than the other. The next series of proportional hazards regression models estimated the hazard ratio of accidental overdose for each diagnosis, individually adjusting for age group, gender, VA priority status, and Charlson comorbidity score (these covariates were used in all further analyses as well). Next, we created models for each of the non-substance use disorder diagnoses, individually adjusted for the same covariates as well as substance use disorder status. Additional analyses included models for each of the non-substance use disorder diagnoses, individually stratified by substance use disorder status; a set of models of the association of substance use disorder status with the outcome among just those individuals with each of the non-substance use disorder diagnoses; and models examining the association of each diagnosis with medication-related and alcohol/illegal drug-related accidental overdoses separately. The denominator for all Cox proportional hazards regression analyses was person-years of risk time. For each individual in the cohort, time of observation began the first day of fiscal year 2000 and ended on the last day of fiscal year 2006 or at the date
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A ccide n ta l O v erdose a n d P s y c h ia t ric a n d S ubs ta n ce U se D isorders TA B L E 1 . D e m o g ra p h ic a n d D ia g n o stic C h a ra c te ristic s a n d U n a d ju ste d A n a ly se s o f A sso c ia tio n W ith A c c id e n ta l O v e rd o se M o rta lity A m o n g Ve te ra n s H e a lth A d m in istra tio n P a tie n ts All Patients Characteristic Total Demographic characteristics Male Age group (years) 18–29 (reference) 30–39 40–49 50–59 60–69 70–79 ≥80 Charlson comorbidity score ≥1 Psychiatric diagnoses Any substance use disorder Alcohol use disorders Drug use disorders Cannabis use disorders Stimulant use disorders Opioid use disorders Other drug use disorders Bipolar I or II disorder Any depressive disorder Major depressive disorder Other depressive disorder Posttraumatic stress disorder Other anxiety disorder Schizophrenia a All p values
