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Incident Substance Use Disorder Following Anxiety Disorder in Privately Insured Youth
Journal of Adolescent Health xxx (2019) 1e7
www.jahonline.org Original article
Incident Substance Use Disorder Following Anxiety Disorder in Privately Insured Youth Greta A. Bushnell, Ph.D. a, *, Bradley N. Gaynes, M.D., M.P.H. b, Scott N. Compton, Ph.D. c, Stacie B. Dusetzina, Ph.D. d, Mark Olfson, M.D., M.P.H. a, e, and Til Stürmer, M.D., Ph.D. f a
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina c Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina d Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee e Department of Psychiatry, Columbia University Irving Medical Center, New York, New York f Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina b
Article history: Received February 8, 2019; Accepted May 9, 2019 Keywords: Substance-related disorders; Anxiety disorders; Child; Adolescent
A B S T R A C T
Purpose: Anxiety disorders in childhood might be associated with an increased risk of substance use disorders. Incident substance useerelated diagnoses were quantified in the 2 years after youth were newly diagnosed with an anxiety disorder and in a similar cohort of youth without diagnosed anxiety. Methods: Privately insured youth (10e17 years) were identified in a commercial claims database who were newly diagnosed with an anxiety disorder (2005e2014), treatment naïve, and without baseline substance-related disorder diagnoses. The comparison cohort included age, sex, region, and date matched youth with equivalent baseline exclusions. We used KaplaneMeier estimator to calculate 2-year cumulative incidence of substance use disorder diagnosis following a new officebased anxiety disorder diagnosis (or match date for comparison cohort). Results: In 131,271 youth with a new anxiety disorder diagnosis (male ¼ 41%, median age ¼ 14 years), 1.5% (95% confidence interval ¼ 1.5e1.6) had an incident substance use disorder diagnosis 1 year after their anxiety diagnosis, 2.9% (95% confidence interval ¼ 2.8e3.0) by 2 years. Over the same period, .5% and 1.1% of the comparison cohort had incident substance use disorder diagnoses (n ¼ 1,321,701). In the anxiety cohort, 2-year incidence was higher in youth aged 14 e17 years (4.6%) versus 10e13 years (.7%). Incidence of substance use diagnosis varied by anxiety disorder (e.g., 2-year incidence: 4.3% for post-traumatic stress disorder, 3.0% for generalized anxiety disorder).
Conflicts of interest: B.N.G., S.B.D., and M.O. report no financial interests or potential conflicts of interest. G.A.B. received research support from the National Institute of Mental Health (Bethesda, MD) under Award Number F31MH107085 (G.A.B.) and under T32MH013043. T.S. receives investigator-initiated research funding and support as Principal Investigator (R01 AG056479) from the National Institute on Aging (NIA) and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of Comparative Effectiveness Research (CER), NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR002489), the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck, Shire), and from pharmaceutical companies (Amgen, AstraZeneca, Novo Nordisk) to the Department of Epidemiology, University of North Carolina at Chapel Hill. T.S. does not accept personal compensation of any kind from any pharmaceutical company. He owns stock in Novartis, Roche, BASF, 1054-139X/Ó 2019 Society for Adolescent Health and Medicine. All rights reserved. https://doi.org/10.1016/j.jadohealth.2019.05.007
IMPLICATIONS AND CONTRIBUTION
Within 2 years of a new office-based anxiety diagnosis, 3% of youth had incident substance use disordererelated diagnoses, almost threefold the incidence in similar youth without anxiety diagnoses, emphasizing the need for increased awareness and prevention of substance use disorders in youth with anxiety. These estimates help anticipate healthcare utilization for substancerelated disorders.
AstraZeneca, and Novo Nordisk. S.N.C. receives research support from the National Institute of Mental Health, NC GlaxoSmithKline Foundation, Mursion, Inc. and has been a consultant for Shire, received honoraria from the Journal of Consulting and Clinical Psychology, Nordic Long-Term OCD Treatment Study Research Group, and The Centre for Child and Adolescent Mental Health, Eastern and Southern Norway, and given expert testimony for Duke University. Disclaimer: This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Source of data: Copyright Ó2016 Truven Health Analytics Inc. All Rights Reserved. * Address correspondence to: Greta A. Bushnell, Ph.D., Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, Room 720c, New York, NY 10032. E-mail address: [email protected] (G.A. Bushnell).
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Conclusion: Approximately 3% of youth newly diagnosed with anxiety received an incident substance use disorder diagnosis within 2 years, almost threefold the incidence in youth without an anxiety diagnosis, emphasizing the need for increased awareness and prevention of substancerelated disorders in pediatric anxiety. Ó 2019 Society for Adolescent Health and Medicine. All rights reserved.
Anxiety disorders often begin during childhood [1,2] and are highly prevalent, affecting more than 5% of youth in the U.S. [3,4]. Despite significant functional [5,6] and academic impairments [7] associated with anxiety disorders in children, only approximately 20%e60% of children receive treatment [4,8,9]. Anxiety disorders often co-occur with other mental disorders including substance use disorders. [10e12] Alcohol abuse and drug abuse have been observed in 17% and 20%, respectively, of youth with prior nonphobic anxiety disorders [13]. Substance use disorders often begin in teenage years [2] and pose a significant public health problem. Nearly 22 million individuals aged 12 years in the U.S. are estimated to have past year substance use disorders, 5% of youth aged 12e17 years [14]. In the U.S., substance use disorders are the second most common chronic condition in pediatric hospitalizations [15], account for prolonged emergency department stays [16], and are associated with high economic costs [17,18]. Mental disorders, including anxiety disorders, are risk factors in the progression to substance use and from substance use to substance-related problems in adolescents [13]. Pediatric anxiety disorders have been associated with subsequent alcohol and drug abuse and dependence [13,19e22], although this finding has been inconsistent. A recent meta-analysis concluded that youth with anxiety disorders did not have a statistically significant increased risk for addiction (pooled odds ratio [OR] ¼ 1.15, 95% confidence interval [CI]: .90e1.55) or substance use disorders (pooled OR ¼ 1.22, 95% CI: .82e1.81), for the subset of studies with substance use disorders as the outcome [23]. Furthermore, studies have found heterogeneity in the strength of associations between specific anxiety disorders and subsequent substance use disorders [13,20,23]. Self-medication and shared risk factors may contribute to the co-occurrence of mental health and substance-related disorders [23e29]. Greater clinical and public health awareness is needed concerning the risk of substance-related disorders in youth seeking care for mental illnesses [23]. The current research builds upon literature on the association between anxiety and substance use disorders and upon prevalence estimates of substance use disorders in youth with anxiety by estimating the proportion of privately insured youth who develop new substance useerelated problems after being diagnosed with an anxiety disorder. Documenting the incidence of substance use disorders during the period following a new anxiety disorder diagnosis can help providers anticipate how often youth may experience substance use problems, convey the risk of substance use disorders to facilitate early detection, underscore the importance of effectively managing anxiety symptoms in young people, and inform discussions on treatment. Furthermore, estimates in comparable youth without anxiety diagnoses help contextualize substance use concerns for youth with anxiety disorders. Anxiety disorders are our focus, as they are prevalent and given the absence of prior estimates on the frequency with which youth newly diagnosed
with anxiety disorders receive incident substance useerelated diagnoses. In youth without baseline substance use diagnoses, authors quantified substance useerelated health care contact in the 2 years after youth were newly diagnosed with an anxiety disorder, and, for comparison, in a similar cohort of youth without diagnosed anxiety. Methods A previously defined study cohort [30] within MarketScan commercial claims database was analyzed that included treatment-naïve, commercially insured U.S. youth (aged 3e17 years) newly diagnosed with an anxiety disorder in an office setting (defined through place of service variable) from 2005 to 2014. Anxiety disorders included International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses corresponding to anxiety disorders in the DSM-V (unspecified anxiety, panic disorder without agoraphobia, generalized anxiety disorder, other anxiety: 300.0x; phobic disorders: 300.2x; separation anxiety disorder: 309.21; anxiety disorder in conditions classified elsewhere: 293.84; selective mutism: 313.23), along with post-traumatic stress disorder (PTSD; 309.81) and obsessive-compulsive disorder (OCD; 300.3x), which were previously classified under “anxiety disorders” in DSM-IV. Youth were identified at the date of new anxiety diagnosis with at least 1 year of prior insurance enrollment. Youth with selected diagnoses (bipolar disorder [ICD-9-CM: 296.0x, 296.4xe.8x], personality disorder [301.x], schizophrenia [295.x], autistic disorder [299.00]) or treatment (psychotherapy claims or selective serotonin reuptake inhibitor, anxiolytic benzodiazepines, buspirone, other antidepressant, hydroxyzine, or antipsychotic prescriptions) in the prior year or with a new anxiety diagnosis outside an office setting were excluded. These exclusions were applied to increase the likelihood of identifying children with new anxiety diagnoses (no prior treatments for anxiety) and create a more clinically relevant cohort of youth without comorbid conditions involving complex treatment regimens. Creation of the comparison cohort has been previously described [30]. Briefly, all children in the database were eligible as potential controls. We matched children on age, sex, geographical region (North Central, Northeast, South, West), and outpatient visit date. The match on visit date required children in the comparison cohort to have a nonanxiety diagnostic code on the exact date as the matched child was diagnosed with anxiety. We applied identical baseline exclusions to the anxiety cohort and controls, selecting up to 10 matches for each child in the anxiety cohort (anxiety cohort: 198,450; comparison: 1,980,082) [30]. For this analysis, anxiety and comparison cohorts were restricted to those without a substance-related disorder diagnosis in available patient history with data beginning in 2000 (1.1%, n ¼ 2,263, of anxiety cohort and .5%, n ¼ 10,387, of
G.A. Bushnell et al. / Journal of Adolescent Health xxx (2019) 1e7
comparison cohort excluded) and youth aged 10e17 years at their new anxiety disorder diagnosis (33% of anxiety and comparison cohorts excluded). Children aged 10e17 years were the focus, given the low risk of substance use in younger children [31]. Substance disorder diagnoses were defined broadly for baseline exclusion: alcohol-induced (291.x) and drug-induced (292.x) mental disorders, alcohol (303.x) and drug (304.x) dependence, nondependent abuse of drugs (305.x), poisoning by opiates and related narcotics (965.0x), sedatives and hypnotics (967.x), or cocaine (970.81), toxic effect of ethyl alcohol (980.0x), and claims related to pregnancy or postpartum drug use (648.3x; 655.5x; 760.7x). Youth were followed from the day after their new officebased anxiety disorder diagnosis or office visit for up to 2 years for incident substance use disorder claims (303-305, excluding “in remission” codes and tobacco use disorder, 305.1). For a secondary definition, we used the expanded substance use definition used in the baseline exclusion criteria mentioned previously. Statistical analysis We used KaplaneMeier estimator to calculate the cumulative incidence of substance use disorder diagnoses following a new office-based anxiety disorder diagnosis, assuming noninformative censoring. Youth were censored at first event, insurance disenrollment, end of data (December 31, 2014), or after 2 years of follow-up, whichever came first. Results were stratified by sex and age at diagnosis, and to provide estimates in youth without other mental health diagnoses, which were more common in the anxiety cohort than comparison cohort, incidence was estimated in youth with no baseline mental disorder diagnoses (except anxiety in the anxiety cohort). The anxiety cohort was further stratified by specific anxiety disorder diagnosis and mental health diagnoses in the baseline year (only anxiety diagnosis; depression diagnosis [296.2x, 296.3x, 300.4x, 309.1x, or 311.xx]; other mental disorder diagnosis [290e319]) to determine if incidence varied by comorbid mental disorder diagnoses. For a sensitivity analysis, results were stratified by youth with and without a follow-up anxiety disorder diagnosis within 90 days of their first anxiety diagnosis. The University of North Carolina at Chapel Hill Institutional Review Board approved this study. Analyses were completed in SAS (version 9.4, Cary, NC). Results The study included 131,271 youth with a new office-based anxiety disorder diagnosis (boys ¼ 41%, median age ¼ 14 years, interquartile range ¼ 12e16), and the comparison cohort included 1,321,701 youth (Table 1). More than half of the anxiety cohort had an unspecified anxiety diagnosis (53%), and 44% were diagnosed with anxiety by a psychiatrist or psychologist/therapist, 20% by a pediatrician, and 13% by a family medicine practitioner. Six months after a new office-based anxiety diagnosis, .8% (95% CI ¼ .8e.9) of youth had received an incident substance use disorder diagnosis, 1.5% (95% CI ¼ 1.5e1.6) by 1 year, and 2.9% (95% CI ¼ 2.8e3.0) by 2 years (Table 2). In the comparison cohort, .2%, .5%, and 1.1% had an incident substance use disorder diagnosis in the 6 months, 1 year, and 2 years, respectively, after their match date. Under the expanded substance use disorder
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definition, 4.0% of youth in the anxiety cohort, and 1.6% in the comparison cohort had an incident recorded substance use disorder within 2 years after their new anxiety diagnosis or match date (Table 2). The cumulative incidence of substance use disorder diagnoses was higher in boys than girls and was substantially higher in youth aged 14e17 years (1 year ¼ 2.5%, 95% CI ¼ 2.4e2.6) than in those aged 10e13 years (1 year ¼ .3%, 95% CI ¼ .2e.3) at their anxiety disorder diagnosis (Table 2). Within both age groups, youth with comorbid depression diagnosis had a higher cumulative incidence of substance use disorder diagnosis than youth without a baseline comorbid mental health diagnosis (Figure 1, Table 2). When restricting the comparison cohort to youth without a baseline mental disorder diagnosis (N ¼ 1,208,981; 91%), the cumulative incidence of substance use disorder diagnoses was approximately one third of the incidence in youth with anxiety and no comorbid mental health diagnosis (Table 2). Considering the more common anxiety disorder diagnoses, the 1-year incidence was 2.2% (95% CI ¼ 1.8e2.7) in youth with PTSD (n ¼ 5,494; 4%), 1.9% (95% CI ¼ 1.6e2.3) in youth with panic disorder (n ¼ 5,784; 4%), 1.6% (95% CI ¼ 1.5e1.7) in youth with an unspecified anxiety diagnosis (n ¼ 70,108; 53%), 1.6% (95% CI ¼ 1.4e1.7) in youth with generalized anxiety disorder (n ¼ 34,008; 26%), and 1.1% (95% CI ¼. 8e1.4) in youth with OCD (n ¼ 6,272; 5%). Two-year incidence followed a similar pattern: PTSD 4.3%, panic disorder 3.4%, unspecified anxiety 2.9%, generalized anxiety disorder 3.0%, and OCD 2.3%, higher than the 2-year incidence in the comparison cohort (1.1%). Fifty-seven percent (n ¼ 74,642) of youth in the anxiety disorder cohort had one or more follow-up anxiety disorder diagnoses within 90 days. The cumulative incidence of incident substance use disorder diagnoses at 1 year was 1.7% (95% CI: 1.6e 1.9) in youth with one or more follow-up diagnoses and 1.3% (1.2e1.4) in youth without them. Discussion Two years after a new office-based anxiety diagnosis, 3% of privately insured U.S. youth had a new substance use disordere related insurance claim, almost threefold the incidence in similar youth without an anxiety diagnosis. The 2-year incidence is particularly striking given our restrictive substance use definition and the baseline exclusions of any substance-related diagnoses and selected mental disorder diagnoses. Together with the high incidence and prevalence of pediatric anxiety diagnoses, our findings highlight the need for clinical awareness, prevention, and early detection of substance-related problems in this population. Generally, prior studies examining the relationship between childhood anxiety disorders and subsequent substance use disorders in community epidemiologic samples report a heightened risk [13,19,20,23,24]. But there have been inconsistent findings. Importantly, clinical diagnostic and severity details and baseline substance use were unavailable in the present analysis, which may differ between anxiety and comparison cohorts. These factors, among others, prevent us from making causal claims surrounding anxiety disorders and substance useerelated diagnoses. Nevertheless, we observed that incident substance useerelated diagnoses are more common in youth with new office-based anxiety diagnoses than in similar youth without anxiety. This has implications for anxiety disorder management and will hopefully encourage follow-up discussions on drug and alcohol use.
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Table 1 Youth (10e17 y) in the anxiety disorder cohort and the comparison cohort Anxiety disorder cohort (N¼131,271)
Original matching factorsa Male Age, median (IQR) 10e13 y 14e17 y Youth characteristics, prior year unless specified Anxiety-related symptoms, prior 90 db Mental health diagnoses Any mental health diagnosisc Depression Adjustment disorder ADHD Sleep disorder General medical diagnoses Acne Allergic rhinitis Asthma Cardiac disorder Diabetes Epilepsy, convulsions Fainting, dizziness Gastroesophageal reflux disease Migraine, chronic headache Fracture, sprain Head injury Opioid prescription Medication therapeutic classes, median (IQR) Well, preventative visit Outpatient, problem-oriented visits, median (IQR) ER visit, 1þ
Comparison cohort (N¼1,321,701)
No.
%
No.
%
54,062 14 (12e16) 56,320 74,951
41
41
43 57
546,346 14 (12e16) 562,492 759,209
21,219
16
104,214
8
34,511 10,807 4,409 14,951 3,704
26 8 3 11 3
112,720 14,398 18,984 65,426 7,737
9 1 1 5 1
14,449 15,133 11,562 2,434 888 1,514 6,033 3,753 3,437 20,466 4,345 13,368 2 (1e3) 72,359 3 (1e5) 25,198
11 12 9 2 1 1 5 3 3 16 3 10
143,373 118,053 91,291 12,962 8,539 9,492 29,676 13,006 18,996 239,219 38,837 135,269 1 (0e3) 792,868 2 (1e4) 215,097
11 9 7 1 1 1 2 1 1 18 3 10
55 19
43 57
60 16
Data source: MarketScan commercial claims (2005e2014). ADHD ¼ attention deficit/hyperactivity disorder; ER ¼ emergency room; IQR ¼ interquartile range. a Cohorts additionally matched on diagnosis date (2005e2006 ¼ 8%, 2007e2009 ¼ 18%, 2010e2012 ¼ 39%, 2013e2014 ¼ 35%) and geographical region (northeast ¼ 21%, north central ¼ 27%, south ¼ 31%, west ¼ 20%, unknown ¼ 1%) before baseline substance use diagnosis exclusion. b International Classification of Diseases, Ninth Revision, Clinical Modification code for abdominal pain, unspecified chest pain, headache, hyperventilation, malaise/ fatigue, nausea, palpations, or weight loss. c Disorders excluded at baseline (substance use disorder, bipolar disorder, schizophrenia, personality disorder, autistic disorder) not included.
Incident substance useerelated diagnoses varied by specific anxiety disorder. Although most anxiety disorders predict at least one form of substance abuse or dependence, the relationship varies by specific anxiety diagnosis and the specific substance use outcome [13,20]. Children diagnosed with PTSD had the highest 2-year incidence of substance-related outcomes in our sample (4.3%); the association between PTSD and future substance-related outcomes has been observed more consistently than for other anxiety disorders [13,20,22,23]. The prevalence of alcohol and drug abuse was found to be higher in adolescents with nonphobic anxiety disorders (generalized anxiety disorder, panic disorder, PTSD) than phobic disorders [13]. Relatedly, the proportion of persons reporting selfmedication (8%e36%) varies by anxiety disorder [27]. Lifetime prevalence of substance use disorders was substantially higher in older than younger youth [2], which is consistent with the much lower 2-year incidence observed in youth aged 10e13 years at anxiety diagnosis compared with 14e17 years. We lack information on age of symptom onset, but anxiety onset in early versus later childhood may also affect the risk of subsequent substance use disorders [21]. Generally, the prevalence of substance use disorders is higher in adolescent males than females [2], and a marginally higher substance use diagnosis
incidence was observed in boys than girls. Age at anxiety diagnosis, sex, and specific anxiety disorder may be important factors to consider in identifying youth at heightened risk for substance use problems. Many individuals with substance use disorders do not seek treatment [32], and there are often long delays between disorder onset and treatment [33], with an estimated 10% making treatment contact within 1 year [34]. The true incidence was underestimated in the present analysis because many individuals with substance-use problems have no medical contact. Still, the incidence estimates capture cases with substance useerelated healthcare contact, which is perhaps the population that can be most readily intervened on and likely in greatest need of follow-up care. Individuals with mental health and substance use disorders are more frequent emergency department users than individuals with substance use disorders alone or no disorder [35,36], highlighting the high healthcare utilization of youth with comorbid mental health and substance use disorders. Estimates of incident substance useerelated diagnoses assist in anticipating healthcare utilization and the need for substance use services in children with anxiety disorders.
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Table 2 Incident substance use disorder diagnoses in youth (10e17 y) with a new office-based anxiety diagnosis and in the comparison cohort Total No
Anxiety cohort, full Male Female Age at anxiety diagnosis 10e13 y 14e17 y No mental health comorbidityc 10e13 y 14e17 y Comparison cohort, full No mental health comorbidity 10e13 y 14e17 y
Substance use disorder, primary definitiona
Expanded substance use disorder definitionb
1y
1y
2y
No. of events
Incidence (95% CI)
131,271 54,062 77,209
1,655 902 753
1.5 (1.5e1.6) 2.0 (1.9e2.1) 1.2 (1.1e1.3)
56,320 74,951
126 1,529
41,067 55,693 1,321,701 510,098 698,883
No. of events
2y
Incidence (95% CI)
No. of events
Incidence (95% CI)
No. of events
Incidence (95% CI)
2,571 1,364 1,207
2.9 (2.8e3.0) 3.7 (3.5e3.9) 2.4 (2.3e2.6)
2,195 1,128 1,067
2.1 (2.0e2.1) 2.5 (2.4e2.7) 1.7 (1.6e1.8)
3,511 1,753 1,758
4.0 (3.9e4.2) 4.7 (4.5e5.0) 3.5 (3.4e3.7)
.3 (.2e.3) 2.5 (2.4e2.6)
251 2,320
.7 (.6e.8) 4.6 (4.4e4.8)
175 2,020
.4 (.3e.5) 3.3 (3.2e3.4)
330 3,200
.9 (.8e1.1) 6.4 (6.2e6.6)
86 968 5,718
.3 (.2e.3) 2.1 (2.0e2.2) .5 (.5e.5)
173 1,521 10,581
.7 (.6e.8) 4.0 (3.8e4.2) 1.1 (1.1e1.1)
117 1,305 7,677
.3 (.3e.4) 2.8 (2.7e3.0) .7 (.7e.7)
216 2,129 14,710
.8 (.7e.9) 5.7 (5.4e5.9) 1.6 (1.5e1.6)
251 4,046
.1 (.1e.1) .7 (.6e.7)
666 7,557
.2 (.2e.2) 1.4 (1.4e1.5)
367 5,528
.1 (.1e.1) .9 (.9e.9)
905 10,720
.3 (.3e.3) 2.0 (2.0e2.1)
Data source: MarketScan commercial claims (2005e2014). CI ¼ confidence interval. a 303e305 excluding ICD-9-CM codes ending in 303e305.x3 as they signify “in remission” and tobacco use disorder (305.1). b 291.x (alcohol-induced mental disorders); 292.x (drug-induced mental disorders); 303.x (alcohol dependence syndrome); 304.x (drug dependence); 305.x (nondependent abuse of drugs); 648.3x (drug dependence complicating pregnancy childbirth or the puerperium); 655.5x (suspected damage to fetus from drugs affecting management of mother); 760.7x (noxious influences affecting fetus or newborn via placenta or breast milk); 965.0x (poisoning by opiates and related narcotics); 967.x (poisoning by sedatives and hypnotics); 970.81 (poisoning by cocaine); 980.0x (toxic effect of ethyl alcohol). c 1-year cumulative incidences (primary definition): youth with baseline depression diagnosis: 10e13 y ¼ .7 (.4e1.1), 14e17 y ¼ 4.6 (4.1e5.2); youth with another baseline mental health diagnosis (excludes youth with depression and diagnoses part of exclusion criteria: bipolar disorder, schizophrenia, autistic disorder, personality disorder): 10e13 y ¼ .3 (.2e.4), 14e17 y ¼ 3.1 (2.7e3.5).
Treating the primary mental disorder may be an important strategy to prevent secondary substance use disorders [13]. In a small sample (n ¼ 86) of U.S. youth with anxiety, those who did not respond to 16-week cognitive behavioral treatment reported higher amounts of substance use, but not substance use disorders, at an average of 7 years later (aged 15e22 years) than youth who responded to treatment [37]. Substance use prevention programs for adolescents have advanced in recent decades and include school, family, and community-based programs, providing promising avenues to prevent substance use disorders [38].
This analysis focused on alcohol or drug-related substance use diagnostic codes and did not distinguish between these diagnoses. Prior literature has found similar alcohol and drug diagnoses in a sample of adolescent substance useerelated emergency department visits, 48% involved alcohol, and 59% involved illicit drugs (7% both) [16]. Past year illicit drug dependence or abuse (3.5%) in U.S. youth aged 12e17 years was slightly higher than alcohol dependence or abuse (2.8%), with 5.2% having either [14]. Future research can expand on our results by examining specific alcohol and drug disorder diagnoses across healthcare settings (inpatient, emergency room, outpatient).
Figure 1. Incident substance use disorder diagnosis by age at office-based anxiety diagnosis and baseline comorbid depression diagnosis. *No comorbid mental health diagnosis at baseline. MarketScan commercial claims database, youth newly diagnosed with anxiety from 2005 to 2014; Not displayed: youth with another comorbid mental health diagnosis (included N ¼ 107,567).
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The results should be interpreted in light of several limitations. Cohort inclusion criteria increased the likelihood children were identified at the time of a new anxiety diagnosis; however, some identified patients may not have had true new diagnoses and exclusions may have removed children previously treated for other mental illnesses. Estimates are based on ICD-9-CM claims for substance use disorders. In adults, ICD-9CM codes for substance use disorders have low sensitivity compared with medical records [39]. Substance use disorders may have been present and undiagnosed at baseline, although best practice guidelines recommend evaluation of comorbid conditions in the assessment and treatment of anxiety disorders [5]. Youth receiving care for an anxiety disorder may, on average, have more opportunities to disclose substance use problems to providers than youth in the comparison cohort; thus, increasing the likelihood that a substance use disorder claim would be recorded, if present. Although our estimates are clinically useful for treatment-naïve patients receiving anxiety diagnoses without prior substance-related diagnoses, this does not represent all youth with anxiety disorders including youth who do not seek medical attention for anxiety disorders [9,33]. In creating the comparison cohort, baseline substance use disorder exclusion was applied after the comparison cohort was matched on age, sex, region, and office visit date, thereby breaking the match. Finally, results are presented for privately insured youth and might differ in uninsured or publicly insured youth. Treatment use differed in adolescents with mental health diagnoses covered by Medicaid versus private insurance [40], and in the 2016 National Survey of Children’s Health, differences were present in anxiety diagnoses, but similar treatment use was observed in children with public or private insurance only [4]. Quantifying the 2-year incidence of substance use disorder diagnoses in youth with anxiety disorders can assist clinicians in conveying risks to patients and their families at the time of anxiety diagnosis. The results also inform clinical efforts to improve the early detection and treatment of substance use problems in this patient population and anticipate substance use-related healthcare utilization. Acknowledgments Author contribution: G.A.B. authored the first draft of the article. Funding Sources Research reported in this publication was supported by the National Institute of Mental Health (Bethesda, MD) under Award Number F31MH107085 (G.A.B.) and under T32MH013043. The funding source had no role in the study design; collection, analysis and interpretation of data; writing of the report; and decision to submit the article for publication. The database infrastructure was funded by the Department of Epidemiology, UNC Gillings School of Global Public Health, the Cecil G. Sheps Center for Health Services Research, UNC, the CER Strategic Initiative of UNC’s Clinical Translational Science Award (UL1TR002489), and the UNC School of Medicine.
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G.A. Bushnell et al. / Journal of Adolescent Health xxx (2019) 1e7 [23] Groenman AP, Janssen TWP, Oosterlaan J. Childhood psychiatric disorders as risk factor for subsequent substance abuse: A meta-analysis. J Am Acad Child Adolesc Psychiatry 2017;56:556e69. [24] O’Neil KA, Conner BT, Kendall PC. Internalizing disorders and substance use disorders in youth: Comorbidity, risk, temporal order, and implications for intervention. Clin Psychol Rev 2011;31:104e12. [25] U.S. Department of Health & Human Services. Mental health and substance use disorders. Available at: https://www.mentalhealth.gov/what-to-lookfor/mental-health-substance-use-disorders. Accessed December 6, 2018. [26] Khantzian EJ. The self-medication hypothesis of addictive disorders: Focus on heroin and cocaine dependence. Am J Psychiatry 1985;142: 1259e64. [27] Turner S, Mota N, Bolton J, Sareen J. Self-medication with alcohol or drugs for mood and anxiety disorders: A narrative review of the epidemiological literature. Depress Anxiety 2018;35:851e60. [28] Menary KR, Kushner MG, Maurer E, Thuras P. The prevalence and clinical implications of self-medication among individuals with anxiety disorders. J Anxiety Disord 2011;25:335e9. [29] Robinson J, Sareen J, Cox BJ, Bolton JM. Role of self-medication in the development of comorbid anxiety and substance use disorders: A longitudinal investigation. Arch Gen Psychiatry 2011;68:800e7. [30] Bushnell GA, Gaynes BN, Compton SN, et al. Incidence of mental health hospitalizations, treated self-harm, and emergency room visits following new anxiety disorder diagnoses in privately insured U.S. children. Depress Anxiety 2019;36:179e89. [31] Sung M, Erkanli A, Angold A, Costello EJ. Effects of age at first substance use and psychiatric comorbidity on the development of substance use disorders. Drug Alcohol Depend 2004;75:287e99.
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[32] Grant BF, Saha TD, Ruan WJ, et al. Epidemiology of DSM-5 drug use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. JAMA Psychiatry 2016;73:39e47. [33] Wang PS, Berglund P, Olfson M, et al. Failure and delay in initial treatment contact after first onset of mental disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:603e13. [34] Wang PS, Angermeyer M, Borges G, et al. Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization’s World Mental Health Survey initiative. World Psychiatry 2007;6: 177e85. [35] Vu F, Daeppen JB, Hugli O, et al. Screening of mental health and substance users in frequent users of a general Swiss emergency department. BMC Emerg Med 2015;15:27. [36] Curran GM, Sullivan G, Williams K, et al. The association of psychiatric comorbidity and use of the emergency department among persons with substance use disorders: An observational cohort study. BMC Emerg Med 2008;8:17. [37] Kendall PC, Safford S, Flannery-Schroeder E, Webb A. Child anxiety treatment: Outcomes in adolescence and impact on substance use and depression at 7.4-year follow-up. J Consult Clin Psychol 2004;72:276e87. [38] Harrop E, Catalano RF. Evidence-based prevention for adolescent substance use. Child Adolesc Psychiatr Clin N Am 2016;25:387e410. [39] Kim HM, Smith EG, Stano CM, et al. Validation of key behaviourally based mental health diagnoses in administrative data: Suicide attempt, alcohol abuse, illicit drug abuse and tobacco use. BMC Health Serv Res 2012;12:18. [40] Ali MM, Sherman LJ, Lynch S, et al. Differences in utilization of mental health treatment among children and adolescents with Medicaid or private insurance. Psychiatr Serv 2019;70:329e32.
www.jahonline.org Original article
Incident Substance Use Disorder Following Anxiety Disorder in Privately Insured Youth Greta A. Bushnell, Ph.D. a, *, Bradley N. Gaynes, M.D., M.P.H. b, Scott N. Compton, Ph.D. c, Stacie B. Dusetzina, Ph.D. d, Mark Olfson, M.D., M.P.H. a, e, and Til Stürmer, M.D., Ph.D. f a
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina c Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina d Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee e Department of Psychiatry, Columbia University Irving Medical Center, New York, New York f Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina b
Article history: Received February 8, 2019; Accepted May 9, 2019 Keywords: Substance-related disorders; Anxiety disorders; Child; Adolescent
A B S T R A C T
Purpose: Anxiety disorders in childhood might be associated with an increased risk of substance use disorders. Incident substance useerelated diagnoses were quantified in the 2 years after youth were newly diagnosed with an anxiety disorder and in a similar cohort of youth without diagnosed anxiety. Methods: Privately insured youth (10e17 years) were identified in a commercial claims database who were newly diagnosed with an anxiety disorder (2005e2014), treatment naïve, and without baseline substance-related disorder diagnoses. The comparison cohort included age, sex, region, and date matched youth with equivalent baseline exclusions. We used KaplaneMeier estimator to calculate 2-year cumulative incidence of substance use disorder diagnosis following a new officebased anxiety disorder diagnosis (or match date for comparison cohort). Results: In 131,271 youth with a new anxiety disorder diagnosis (male ¼ 41%, median age ¼ 14 years), 1.5% (95% confidence interval ¼ 1.5e1.6) had an incident substance use disorder diagnosis 1 year after their anxiety diagnosis, 2.9% (95% confidence interval ¼ 2.8e3.0) by 2 years. Over the same period, .5% and 1.1% of the comparison cohort had incident substance use disorder diagnoses (n ¼ 1,321,701). In the anxiety cohort, 2-year incidence was higher in youth aged 14 e17 years (4.6%) versus 10e13 years (.7%). Incidence of substance use diagnosis varied by anxiety disorder (e.g., 2-year incidence: 4.3% for post-traumatic stress disorder, 3.0% for generalized anxiety disorder).
Conflicts of interest: B.N.G., S.B.D., and M.O. report no financial interests or potential conflicts of interest. G.A.B. received research support from the National Institute of Mental Health (Bethesda, MD) under Award Number F31MH107085 (G.A.B.) and under T32MH013043. T.S. receives investigator-initiated research funding and support as Principal Investigator (R01 AG056479) from the National Institute on Aging (NIA) and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of Comparative Effectiveness Research (CER), NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR002489), the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck, Shire), and from pharmaceutical companies (Amgen, AstraZeneca, Novo Nordisk) to the Department of Epidemiology, University of North Carolina at Chapel Hill. T.S. does not accept personal compensation of any kind from any pharmaceutical company. He owns stock in Novartis, Roche, BASF, 1054-139X/Ó 2019 Society for Adolescent Health and Medicine. All rights reserved. https://doi.org/10.1016/j.jadohealth.2019.05.007
IMPLICATIONS AND CONTRIBUTION
Within 2 years of a new office-based anxiety diagnosis, 3% of youth had incident substance use disordererelated diagnoses, almost threefold the incidence in similar youth without anxiety diagnoses, emphasizing the need for increased awareness and prevention of substance use disorders in youth with anxiety. These estimates help anticipate healthcare utilization for substancerelated disorders.
AstraZeneca, and Novo Nordisk. S.N.C. receives research support from the National Institute of Mental Health, NC GlaxoSmithKline Foundation, Mursion, Inc. and has been a consultant for Shire, received honoraria from the Journal of Consulting and Clinical Psychology, Nordic Long-Term OCD Treatment Study Research Group, and The Centre for Child and Adolescent Mental Health, Eastern and Southern Norway, and given expert testimony for Duke University. Disclaimer: This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Source of data: Copyright Ó2016 Truven Health Analytics Inc. All Rights Reserved. * Address correspondence to: Greta A. Bushnell, Ph.D., Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, Room 720c, New York, NY 10032. E-mail address: [email protected] (G.A. Bushnell).
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Conclusion: Approximately 3% of youth newly diagnosed with anxiety received an incident substance use disorder diagnosis within 2 years, almost threefold the incidence in youth without an anxiety diagnosis, emphasizing the need for increased awareness and prevention of substancerelated disorders in pediatric anxiety. Ó 2019 Society for Adolescent Health and Medicine. All rights reserved.
Anxiety disorders often begin during childhood [1,2] and are highly prevalent, affecting more than 5% of youth in the U.S. [3,4]. Despite significant functional [5,6] and academic impairments [7] associated with anxiety disorders in children, only approximately 20%e60% of children receive treatment [4,8,9]. Anxiety disorders often co-occur with other mental disorders including substance use disorders. [10e12] Alcohol abuse and drug abuse have been observed in 17% and 20%, respectively, of youth with prior nonphobic anxiety disorders [13]. Substance use disorders often begin in teenage years [2] and pose a significant public health problem. Nearly 22 million individuals aged 12 years in the U.S. are estimated to have past year substance use disorders, 5% of youth aged 12e17 years [14]. In the U.S., substance use disorders are the second most common chronic condition in pediatric hospitalizations [15], account for prolonged emergency department stays [16], and are associated with high economic costs [17,18]. Mental disorders, including anxiety disorders, are risk factors in the progression to substance use and from substance use to substance-related problems in adolescents [13]. Pediatric anxiety disorders have been associated with subsequent alcohol and drug abuse and dependence [13,19e22], although this finding has been inconsistent. A recent meta-analysis concluded that youth with anxiety disorders did not have a statistically significant increased risk for addiction (pooled odds ratio [OR] ¼ 1.15, 95% confidence interval [CI]: .90e1.55) or substance use disorders (pooled OR ¼ 1.22, 95% CI: .82e1.81), for the subset of studies with substance use disorders as the outcome [23]. Furthermore, studies have found heterogeneity in the strength of associations between specific anxiety disorders and subsequent substance use disorders [13,20,23]. Self-medication and shared risk factors may contribute to the co-occurrence of mental health and substance-related disorders [23e29]. Greater clinical and public health awareness is needed concerning the risk of substance-related disorders in youth seeking care for mental illnesses [23]. The current research builds upon literature on the association between anxiety and substance use disorders and upon prevalence estimates of substance use disorders in youth with anxiety by estimating the proportion of privately insured youth who develop new substance useerelated problems after being diagnosed with an anxiety disorder. Documenting the incidence of substance use disorders during the period following a new anxiety disorder diagnosis can help providers anticipate how often youth may experience substance use problems, convey the risk of substance use disorders to facilitate early detection, underscore the importance of effectively managing anxiety symptoms in young people, and inform discussions on treatment. Furthermore, estimates in comparable youth without anxiety diagnoses help contextualize substance use concerns for youth with anxiety disorders. Anxiety disorders are our focus, as they are prevalent and given the absence of prior estimates on the frequency with which youth newly diagnosed
with anxiety disorders receive incident substance useerelated diagnoses. In youth without baseline substance use diagnoses, authors quantified substance useerelated health care contact in the 2 years after youth were newly diagnosed with an anxiety disorder, and, for comparison, in a similar cohort of youth without diagnosed anxiety. Methods A previously defined study cohort [30] within MarketScan commercial claims database was analyzed that included treatment-naïve, commercially insured U.S. youth (aged 3e17 years) newly diagnosed with an anxiety disorder in an office setting (defined through place of service variable) from 2005 to 2014. Anxiety disorders included International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses corresponding to anxiety disorders in the DSM-V (unspecified anxiety, panic disorder without agoraphobia, generalized anxiety disorder, other anxiety: 300.0x; phobic disorders: 300.2x; separation anxiety disorder: 309.21; anxiety disorder in conditions classified elsewhere: 293.84; selective mutism: 313.23), along with post-traumatic stress disorder (PTSD; 309.81) and obsessive-compulsive disorder (OCD; 300.3x), which were previously classified under “anxiety disorders” in DSM-IV. Youth were identified at the date of new anxiety diagnosis with at least 1 year of prior insurance enrollment. Youth with selected diagnoses (bipolar disorder [ICD-9-CM: 296.0x, 296.4xe.8x], personality disorder [301.x], schizophrenia [295.x], autistic disorder [299.00]) or treatment (psychotherapy claims or selective serotonin reuptake inhibitor, anxiolytic benzodiazepines, buspirone, other antidepressant, hydroxyzine, or antipsychotic prescriptions) in the prior year or with a new anxiety diagnosis outside an office setting were excluded. These exclusions were applied to increase the likelihood of identifying children with new anxiety diagnoses (no prior treatments for anxiety) and create a more clinically relevant cohort of youth without comorbid conditions involving complex treatment regimens. Creation of the comparison cohort has been previously described [30]. Briefly, all children in the database were eligible as potential controls. We matched children on age, sex, geographical region (North Central, Northeast, South, West), and outpatient visit date. The match on visit date required children in the comparison cohort to have a nonanxiety diagnostic code on the exact date as the matched child was diagnosed with anxiety. We applied identical baseline exclusions to the anxiety cohort and controls, selecting up to 10 matches for each child in the anxiety cohort (anxiety cohort: 198,450; comparison: 1,980,082) [30]. For this analysis, anxiety and comparison cohorts were restricted to those without a substance-related disorder diagnosis in available patient history with data beginning in 2000 (1.1%, n ¼ 2,263, of anxiety cohort and .5%, n ¼ 10,387, of
G.A. Bushnell et al. / Journal of Adolescent Health xxx (2019) 1e7
comparison cohort excluded) and youth aged 10e17 years at their new anxiety disorder diagnosis (33% of anxiety and comparison cohorts excluded). Children aged 10e17 years were the focus, given the low risk of substance use in younger children [31]. Substance disorder diagnoses were defined broadly for baseline exclusion: alcohol-induced (291.x) and drug-induced (292.x) mental disorders, alcohol (303.x) and drug (304.x) dependence, nondependent abuse of drugs (305.x), poisoning by opiates and related narcotics (965.0x), sedatives and hypnotics (967.x), or cocaine (970.81), toxic effect of ethyl alcohol (980.0x), and claims related to pregnancy or postpartum drug use (648.3x; 655.5x; 760.7x). Youth were followed from the day after their new officebased anxiety disorder diagnosis or office visit for up to 2 years for incident substance use disorder claims (303-305, excluding “in remission” codes and tobacco use disorder, 305.1). For a secondary definition, we used the expanded substance use definition used in the baseline exclusion criteria mentioned previously. Statistical analysis We used KaplaneMeier estimator to calculate the cumulative incidence of substance use disorder diagnoses following a new office-based anxiety disorder diagnosis, assuming noninformative censoring. Youth were censored at first event, insurance disenrollment, end of data (December 31, 2014), or after 2 years of follow-up, whichever came first. Results were stratified by sex and age at diagnosis, and to provide estimates in youth without other mental health diagnoses, which were more common in the anxiety cohort than comparison cohort, incidence was estimated in youth with no baseline mental disorder diagnoses (except anxiety in the anxiety cohort). The anxiety cohort was further stratified by specific anxiety disorder diagnosis and mental health diagnoses in the baseline year (only anxiety diagnosis; depression diagnosis [296.2x, 296.3x, 300.4x, 309.1x, or 311.xx]; other mental disorder diagnosis [290e319]) to determine if incidence varied by comorbid mental disorder diagnoses. For a sensitivity analysis, results were stratified by youth with and without a follow-up anxiety disorder diagnosis within 90 days of their first anxiety diagnosis. The University of North Carolina at Chapel Hill Institutional Review Board approved this study. Analyses were completed in SAS (version 9.4, Cary, NC). Results The study included 131,271 youth with a new office-based anxiety disorder diagnosis (boys ¼ 41%, median age ¼ 14 years, interquartile range ¼ 12e16), and the comparison cohort included 1,321,701 youth (Table 1). More than half of the anxiety cohort had an unspecified anxiety diagnosis (53%), and 44% were diagnosed with anxiety by a psychiatrist or psychologist/therapist, 20% by a pediatrician, and 13% by a family medicine practitioner. Six months after a new office-based anxiety diagnosis, .8% (95% CI ¼ .8e.9) of youth had received an incident substance use disorder diagnosis, 1.5% (95% CI ¼ 1.5e1.6) by 1 year, and 2.9% (95% CI ¼ 2.8e3.0) by 2 years (Table 2). In the comparison cohort, .2%, .5%, and 1.1% had an incident substance use disorder diagnosis in the 6 months, 1 year, and 2 years, respectively, after their match date. Under the expanded substance use disorder
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definition, 4.0% of youth in the anxiety cohort, and 1.6% in the comparison cohort had an incident recorded substance use disorder within 2 years after their new anxiety diagnosis or match date (Table 2). The cumulative incidence of substance use disorder diagnoses was higher in boys than girls and was substantially higher in youth aged 14e17 years (1 year ¼ 2.5%, 95% CI ¼ 2.4e2.6) than in those aged 10e13 years (1 year ¼ .3%, 95% CI ¼ .2e.3) at their anxiety disorder diagnosis (Table 2). Within both age groups, youth with comorbid depression diagnosis had a higher cumulative incidence of substance use disorder diagnosis than youth without a baseline comorbid mental health diagnosis (Figure 1, Table 2). When restricting the comparison cohort to youth without a baseline mental disorder diagnosis (N ¼ 1,208,981; 91%), the cumulative incidence of substance use disorder diagnoses was approximately one third of the incidence in youth with anxiety and no comorbid mental health diagnosis (Table 2). Considering the more common anxiety disorder diagnoses, the 1-year incidence was 2.2% (95% CI ¼ 1.8e2.7) in youth with PTSD (n ¼ 5,494; 4%), 1.9% (95% CI ¼ 1.6e2.3) in youth with panic disorder (n ¼ 5,784; 4%), 1.6% (95% CI ¼ 1.5e1.7) in youth with an unspecified anxiety diagnosis (n ¼ 70,108; 53%), 1.6% (95% CI ¼ 1.4e1.7) in youth with generalized anxiety disorder (n ¼ 34,008; 26%), and 1.1% (95% CI ¼. 8e1.4) in youth with OCD (n ¼ 6,272; 5%). Two-year incidence followed a similar pattern: PTSD 4.3%, panic disorder 3.4%, unspecified anxiety 2.9%, generalized anxiety disorder 3.0%, and OCD 2.3%, higher than the 2-year incidence in the comparison cohort (1.1%). Fifty-seven percent (n ¼ 74,642) of youth in the anxiety disorder cohort had one or more follow-up anxiety disorder diagnoses within 90 days. The cumulative incidence of incident substance use disorder diagnoses at 1 year was 1.7% (95% CI: 1.6e 1.9) in youth with one or more follow-up diagnoses and 1.3% (1.2e1.4) in youth without them. Discussion Two years after a new office-based anxiety diagnosis, 3% of privately insured U.S. youth had a new substance use disordere related insurance claim, almost threefold the incidence in similar youth without an anxiety diagnosis. The 2-year incidence is particularly striking given our restrictive substance use definition and the baseline exclusions of any substance-related diagnoses and selected mental disorder diagnoses. Together with the high incidence and prevalence of pediatric anxiety diagnoses, our findings highlight the need for clinical awareness, prevention, and early detection of substance-related problems in this population. Generally, prior studies examining the relationship between childhood anxiety disorders and subsequent substance use disorders in community epidemiologic samples report a heightened risk [13,19,20,23,24]. But there have been inconsistent findings. Importantly, clinical diagnostic and severity details and baseline substance use were unavailable in the present analysis, which may differ between anxiety and comparison cohorts. These factors, among others, prevent us from making causal claims surrounding anxiety disorders and substance useerelated diagnoses. Nevertheless, we observed that incident substance useerelated diagnoses are more common in youth with new office-based anxiety diagnoses than in similar youth without anxiety. This has implications for anxiety disorder management and will hopefully encourage follow-up discussions on drug and alcohol use.
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Table 1 Youth (10e17 y) in the anxiety disorder cohort and the comparison cohort Anxiety disorder cohort (N¼131,271)
Original matching factorsa Male Age, median (IQR) 10e13 y 14e17 y Youth characteristics, prior year unless specified Anxiety-related symptoms, prior 90 db Mental health diagnoses Any mental health diagnosisc Depression Adjustment disorder ADHD Sleep disorder General medical diagnoses Acne Allergic rhinitis Asthma Cardiac disorder Diabetes Epilepsy, convulsions Fainting, dizziness Gastroesophageal reflux disease Migraine, chronic headache Fracture, sprain Head injury Opioid prescription Medication therapeutic classes, median (IQR) Well, preventative visit Outpatient, problem-oriented visits, median (IQR) ER visit, 1þ
Comparison cohort (N¼1,321,701)
No.
%
No.
%
54,062 14 (12e16) 56,320 74,951
41
41
43 57
546,346 14 (12e16) 562,492 759,209
21,219
16
104,214
8
34,511 10,807 4,409 14,951 3,704
26 8 3 11 3
112,720 14,398 18,984 65,426 7,737
9 1 1 5 1
14,449 15,133 11,562 2,434 888 1,514 6,033 3,753 3,437 20,466 4,345 13,368 2 (1e3) 72,359 3 (1e5) 25,198
11 12 9 2 1 1 5 3 3 16 3 10
143,373 118,053 91,291 12,962 8,539 9,492 29,676 13,006 18,996 239,219 38,837 135,269 1 (0e3) 792,868 2 (1e4) 215,097
11 9 7 1 1 1 2 1 1 18 3 10
55 19
43 57
60 16
Data source: MarketScan commercial claims (2005e2014). ADHD ¼ attention deficit/hyperactivity disorder; ER ¼ emergency room; IQR ¼ interquartile range. a Cohorts additionally matched on diagnosis date (2005e2006 ¼ 8%, 2007e2009 ¼ 18%, 2010e2012 ¼ 39%, 2013e2014 ¼ 35%) and geographical region (northeast ¼ 21%, north central ¼ 27%, south ¼ 31%, west ¼ 20%, unknown ¼ 1%) before baseline substance use diagnosis exclusion. b International Classification of Diseases, Ninth Revision, Clinical Modification code for abdominal pain, unspecified chest pain, headache, hyperventilation, malaise/ fatigue, nausea, palpations, or weight loss. c Disorders excluded at baseline (substance use disorder, bipolar disorder, schizophrenia, personality disorder, autistic disorder) not included.
Incident substance useerelated diagnoses varied by specific anxiety disorder. Although most anxiety disorders predict at least one form of substance abuse or dependence, the relationship varies by specific anxiety diagnosis and the specific substance use outcome [13,20]. Children diagnosed with PTSD had the highest 2-year incidence of substance-related outcomes in our sample (4.3%); the association between PTSD and future substance-related outcomes has been observed more consistently than for other anxiety disorders [13,20,22,23]. The prevalence of alcohol and drug abuse was found to be higher in adolescents with nonphobic anxiety disorders (generalized anxiety disorder, panic disorder, PTSD) than phobic disorders [13]. Relatedly, the proportion of persons reporting selfmedication (8%e36%) varies by anxiety disorder [27]. Lifetime prevalence of substance use disorders was substantially higher in older than younger youth [2], which is consistent with the much lower 2-year incidence observed in youth aged 10e13 years at anxiety diagnosis compared with 14e17 years. We lack information on age of symptom onset, but anxiety onset in early versus later childhood may also affect the risk of subsequent substance use disorders [21]. Generally, the prevalence of substance use disorders is higher in adolescent males than females [2], and a marginally higher substance use diagnosis
incidence was observed in boys than girls. Age at anxiety diagnosis, sex, and specific anxiety disorder may be important factors to consider in identifying youth at heightened risk for substance use problems. Many individuals with substance use disorders do not seek treatment [32], and there are often long delays between disorder onset and treatment [33], with an estimated 10% making treatment contact within 1 year [34]. The true incidence was underestimated in the present analysis because many individuals with substance-use problems have no medical contact. Still, the incidence estimates capture cases with substance useerelated healthcare contact, which is perhaps the population that can be most readily intervened on and likely in greatest need of follow-up care. Individuals with mental health and substance use disorders are more frequent emergency department users than individuals with substance use disorders alone or no disorder [35,36], highlighting the high healthcare utilization of youth with comorbid mental health and substance use disorders. Estimates of incident substance useerelated diagnoses assist in anticipating healthcare utilization and the need for substance use services in children with anxiety disorders.
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Table 2 Incident substance use disorder diagnoses in youth (10e17 y) with a new office-based anxiety diagnosis and in the comparison cohort Total No
Anxiety cohort, full Male Female Age at anxiety diagnosis 10e13 y 14e17 y No mental health comorbidityc 10e13 y 14e17 y Comparison cohort, full No mental health comorbidity 10e13 y 14e17 y
Substance use disorder, primary definitiona
Expanded substance use disorder definitionb
1y
1y
2y
No. of events
Incidence (95% CI)
131,271 54,062 77,209
1,655 902 753
1.5 (1.5e1.6) 2.0 (1.9e2.1) 1.2 (1.1e1.3)
56,320 74,951
126 1,529
41,067 55,693 1,321,701 510,098 698,883
No. of events
2y
Incidence (95% CI)
No. of events
Incidence (95% CI)
No. of events
Incidence (95% CI)
2,571 1,364 1,207
2.9 (2.8e3.0) 3.7 (3.5e3.9) 2.4 (2.3e2.6)
2,195 1,128 1,067
2.1 (2.0e2.1) 2.5 (2.4e2.7) 1.7 (1.6e1.8)
3,511 1,753 1,758
4.0 (3.9e4.2) 4.7 (4.5e5.0) 3.5 (3.4e3.7)
.3 (.2e.3) 2.5 (2.4e2.6)
251 2,320
.7 (.6e.8) 4.6 (4.4e4.8)
175 2,020
.4 (.3e.5) 3.3 (3.2e3.4)
330 3,200
.9 (.8e1.1) 6.4 (6.2e6.6)
86 968 5,718
.3 (.2e.3) 2.1 (2.0e2.2) .5 (.5e.5)
173 1,521 10,581
.7 (.6e.8) 4.0 (3.8e4.2) 1.1 (1.1e1.1)
117 1,305 7,677
.3 (.3e.4) 2.8 (2.7e3.0) .7 (.7e.7)
216 2,129 14,710
.8 (.7e.9) 5.7 (5.4e5.9) 1.6 (1.5e1.6)
251 4,046
.1 (.1e.1) .7 (.6e.7)
666 7,557
.2 (.2e.2) 1.4 (1.4e1.5)
367 5,528
.1 (.1e.1) .9 (.9e.9)
905 10,720
.3 (.3e.3) 2.0 (2.0e2.1)
Data source: MarketScan commercial claims (2005e2014). CI ¼ confidence interval. a 303e305 excluding ICD-9-CM codes ending in 303e305.x3 as they signify “in remission” and tobacco use disorder (305.1). b 291.x (alcohol-induced mental disorders); 292.x (drug-induced mental disorders); 303.x (alcohol dependence syndrome); 304.x (drug dependence); 305.x (nondependent abuse of drugs); 648.3x (drug dependence complicating pregnancy childbirth or the puerperium); 655.5x (suspected damage to fetus from drugs affecting management of mother); 760.7x (noxious influences affecting fetus or newborn via placenta or breast milk); 965.0x (poisoning by opiates and related narcotics); 967.x (poisoning by sedatives and hypnotics); 970.81 (poisoning by cocaine); 980.0x (toxic effect of ethyl alcohol). c 1-year cumulative incidences (primary definition): youth with baseline depression diagnosis: 10e13 y ¼ .7 (.4e1.1), 14e17 y ¼ 4.6 (4.1e5.2); youth with another baseline mental health diagnosis (excludes youth with depression and diagnoses part of exclusion criteria: bipolar disorder, schizophrenia, autistic disorder, personality disorder): 10e13 y ¼ .3 (.2e.4), 14e17 y ¼ 3.1 (2.7e3.5).
Treating the primary mental disorder may be an important strategy to prevent secondary substance use disorders [13]. In a small sample (n ¼ 86) of U.S. youth with anxiety, those who did not respond to 16-week cognitive behavioral treatment reported higher amounts of substance use, but not substance use disorders, at an average of 7 years later (aged 15e22 years) than youth who responded to treatment [37]. Substance use prevention programs for adolescents have advanced in recent decades and include school, family, and community-based programs, providing promising avenues to prevent substance use disorders [38].
This analysis focused on alcohol or drug-related substance use diagnostic codes and did not distinguish between these diagnoses. Prior literature has found similar alcohol and drug diagnoses in a sample of adolescent substance useerelated emergency department visits, 48% involved alcohol, and 59% involved illicit drugs (7% both) [16]. Past year illicit drug dependence or abuse (3.5%) in U.S. youth aged 12e17 years was slightly higher than alcohol dependence or abuse (2.8%), with 5.2% having either [14]. Future research can expand on our results by examining specific alcohol and drug disorder diagnoses across healthcare settings (inpatient, emergency room, outpatient).
Figure 1. Incident substance use disorder diagnosis by age at office-based anxiety diagnosis and baseline comorbid depression diagnosis. *No comorbid mental health diagnosis at baseline. MarketScan commercial claims database, youth newly diagnosed with anxiety from 2005 to 2014; Not displayed: youth with another comorbid mental health diagnosis (included N ¼ 107,567).
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G.A. Bushnell et al. / Journal of Adolescent Health xxx (2019) 1e7
The results should be interpreted in light of several limitations. Cohort inclusion criteria increased the likelihood children were identified at the time of a new anxiety diagnosis; however, some identified patients may not have had true new diagnoses and exclusions may have removed children previously treated for other mental illnesses. Estimates are based on ICD-9-CM claims for substance use disorders. In adults, ICD-9CM codes for substance use disorders have low sensitivity compared with medical records [39]. Substance use disorders may have been present and undiagnosed at baseline, although best practice guidelines recommend evaluation of comorbid conditions in the assessment and treatment of anxiety disorders [5]. Youth receiving care for an anxiety disorder may, on average, have more opportunities to disclose substance use problems to providers than youth in the comparison cohort; thus, increasing the likelihood that a substance use disorder claim would be recorded, if present. Although our estimates are clinically useful for treatment-naïve patients receiving anxiety diagnoses without prior substance-related diagnoses, this does not represent all youth with anxiety disorders including youth who do not seek medical attention for anxiety disorders [9,33]. In creating the comparison cohort, baseline substance use disorder exclusion was applied after the comparison cohort was matched on age, sex, region, and office visit date, thereby breaking the match. Finally, results are presented for privately insured youth and might differ in uninsured or publicly insured youth. Treatment use differed in adolescents with mental health diagnoses covered by Medicaid versus private insurance [40], and in the 2016 National Survey of Children’s Health, differences were present in anxiety diagnoses, but similar treatment use was observed in children with public or private insurance only [4]. Quantifying the 2-year incidence of substance use disorder diagnoses in youth with anxiety disorders can assist clinicians in conveying risks to patients and their families at the time of anxiety diagnosis. The results also inform clinical efforts to improve the early detection and treatment of substance use problems in this patient population and anticipate substance use-related healthcare utilization. Acknowledgments Author contribution: G.A.B. authored the first draft of the article. Funding Sources Research reported in this publication was supported by the National Institute of Mental Health (Bethesda, MD) under Award Number F31MH107085 (G.A.B.) and under T32MH013043. The funding source had no role in the study design; collection, analysis and interpretation of data; writing of the report; and decision to submit the article for publication. The database infrastructure was funded by the Department of Epidemiology, UNC Gillings School of Global Public Health, the Cecil G. Sheps Center for Health Services Research, UNC, the CER Strategic Initiative of UNC’s Clinical Translational Science Award (UL1TR002489), and the UNC School of Medicine.
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