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Opiate-Related Dependence/Abuse and PTSD Exposure Among the Active-Component U.S. Military, 2001 to 2008 Clifton Dabbs, DO, MPH*; Eren Youmans Watkins, PhD, M PHf; David S. Fink, M PHf; Angelia Eick-Cost, PhD, ScM f, Amy M. Miilikan, MD, M PH f
ABSTRACT Background: Over the past 5 years, diagnoses for opiate abuse or dependency and post-traumatic stress disorder (PTSD) have increased across all U.S. military services. Moreover, in the United States, opiate prescription dependence and abuse has now surpassed all other illicit drugs of abuse with the exception of marijuana. Some research indicates that PTSD is predictive of substance dependence and abuse, while other research suggests that substance dependence and abuse may lead to events that trigger PTSD. This dichotomy has not been extensively explored within a military population. Methods: Using conditional multiple logistic regression analysis, a matched case-control study with 18,606 active-component U.S. military service members was conducted to examine the relationship between opiate dependence or abuse and PTSD. Results: Among the 18,606 service members included in the analysis, 21% were cases and 79% were controls. Thirteen percent of service members with substance dependence or abuse diagnosis had a prior PTSD diagnosis compared to 1% of controls. After, adjusting for sociodemographic and military characteristics, the odds of having a prior diagnosis of PTSD was 28 (95% Cl: 21.24-37.78) times greater for service members with opiate abuse/dependency compared to controls. Conclusion: These findings suggest active duty military personnel diagnosed with PTSD should be closely monitored to reduce the likelihood of future morbidity because of opiate dependence or abuse.
INTRODUCTION Over the last decade, opiate dependence, a medical diagnosis characterized by an individual’s inability to stop using opi oids, and opioid abuse, compulsive use of opioids that pose harm to a person’s health or social functioning, have been a rising public health problem .1 In the United States, the annual number of deaths related to prescription opioids now exceeds the number of deaths related to heroin and cocaine com bined.- From 1991 to 2010, the United States experienced a three-fold increase in prescriptions for opioid analgesics (75.5-209.5 million) and prescription opiate dependence and abuse has now surpassed all other illicit drugs of abuse with the exception of marijuana.3 A similar trend is prevalent across U.S. military branches.4 Between 2002 and 2008, pre scription opioid dependence and abuse among Department of Defense service members rose from 1% to 10%.5 More spe cifically, from 2007 to 2010, there was a 700% increase in the rate of opioid dependence and abuse among Soldiers in the U.S. Army.5
*Department of Preventive Medicine, Walter Reed Army Institute of Research, 621 Derringer, Bel Air. MD 21015. tArmy Institute of Public Health, Behavioral and Social Health Out comes Program, 5158 Blackhawk Road, Building 1570, Aberdeen Proving Ground, MD 21010. fArmed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 21090. The views expressed in this article are those of the authors and do not reflect official policy or position of the Department of the Army, the Depart ment of Defense, the U.S. Government or any of the institutional affiliations listed. None of these authors have any conflicts of interest to declare, doi: 10.7205/MILMED-D-14-00012
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Historically, behavioral health problems and psychiatric illnesses have been an issue for service members returning from war.6 } Most recently, 1 in 8 service members returning from Operation Enduring Freedom or Operation Iraqi Free dom have screened positive for post-traumatic stress disorder (PTSD).6 Almost parallel to the increase in the diagnosis of PTSD across the services was the rise in opioid dependence and abuse (Fig. 1 and Fig. 2).5 Although some research indi cates that PTSD is predictive of substance dependence and abuse, 11-15 other research suggests that substance depen dence and abuse increases the likelihood of exposure to trauma, which may lead to PTSD .16 This dichotomy is not fully understood and has not been extensively explored within the military population. Among studies that have been conducted to explore the nexus between PTSD and sub stance, most have been among military veterans.17-19 The objective of this study was to determine whether individuals diagnosed with opiate dependence and abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched controls within a large military population. Moreover, this study will be among the first to unpack the temporal association (not dichotomy) between PTSD and opiate abuse and dependence, which will have significant implications for the identification of prevention and treatment of these disorders.
METHODS Sources of Data This study was conducted using administrative data from the Department of Defense Defense Medical Surveillance System (DMSS) database."0 DMSS contains information on service
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military medical diagnosis for PTSD, was defined as an inpatient or outpatient diagnosis with PTSD (ICD-9: 309.81) in any diag nostic position before the opiate dependency or abuse diagnosis. Military characteristics included branch of service, rank (Enlisted [E] 1 through 9, Commissioned Officer [O] 1 through 9 and Warrant Officers) and deployment history. Much like employees at a company, Enlisted Soldiers perform specific job functions and have the knowledge that ensures the suc cess of their unit’s current mission within the Army. An Enlisted Soldiers rank can range from Private (El) to Ser geant Major of the Army (E9). Commissioned Officers are FIGURE 1. Rate of post-traumatic stress disorder diagnosed among U.S. responsible for completing demanding missions while ensur military service members, 2001 to 2010.5 ing the welfare, morale, and professional development of the Soldiers entrusted to them. An Officer’s rank can range from Second Lieutenant (01) through General (09). Warrant Offi cers are highly specialized experts and trainers in their career fields. Warrant Officers remain single-specialty Officers with career tracks that progress within their field, unlike their Commissioned Officer counterparts who focus on increased levels of command and staff duty positions. Warrant Officers rank can range from Warrant Office 1 through Chief Warrant Officer 5.21 Rank was categorized as El to E4, E5 to E9, Ol to 04, and Warrant Officers. Deployment history was defined as the total number (categorical variable) of deployments before a case’s incident opiate diagnosis. Sociodemographic characteristics included sex, education, FIGURE 2. Rate of opiate dependence diagnosed among U.S. military and marital status. Service members with a high school service members, 2001 to 2010.5 diploma or general education diploma were classified as hav ing a high school education. In addition, service members member’s sociodemographic characteristics, deployment infor with any type of postbaccalaureate degree (e.g., master’s mation, and medical records. Medical data (using International degree, PhD, medical degree) were collapsed into a single Classification of Disease, Ninth Revision (ICD-9-CM) codes) category (> master’s degree). Time-varying covariates were in DMSS are generated from billing code data on inpatient and provided at the time of the case’s diagnosis date. Five hun outpatient clinical visits occurring at military treatment facili dred sixty-nine service members with missing information on ties and outsourced care. The Walter Reed Army Institute of education were classified as Unknown. Marital status was Research Institutional Review Board approved this study and categorized as married, single, and other. A total of 18,606 assigned protocol no. 1712. service members were included in the analysis. Study Population A nested case-control study was conducted among activecomponent U.S. service members from the five branches (Air Force, Army, Coast Guard, Marines, and Navy) of ser vice. Cases were defined as service members, who served at any time from 2001 to 2008 and had a first-time diagnosis of opiate dependency (ICD-9: 304.00, 304.01, 304.02, 304.70, 304.71, or 304.72) or opiate abuse (ICD-9:305.50, 305.51, or 305.52) that occurred from 2001 to 2008 in any diagnostic position during one inpatient or at least two separate outpatient visits within a 365-day period. Controls were defined as active duty service members who did not have a diagnosis for opiate drug dependency or abuse within the Military Health System database. Each case was matched with up to four controls by date of birth (±1 year), date of accession into the military (±1 year), and active-component status on the date of the case’s first opiate (incident) diagnosis. The exposure of interest, a
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Statistical Analyses Frequency distributions were examined for all of socio demographic and military characteristics and percentages were used to describe categorical variables. Conditional multiple logistic regression modeling was conducted to determine the association between an incident diagnosis of opiate depen dency or abuse and PTSD while controlling for the aforemen tioned sociodemographic and military characteristics known to be associated with PTSD and opiate dependency or abuse. Adjusted odds ratios (aOR) and 95% confidence intervals (95% Cl) are reported. Data analysis was performed using SAS v. 9.2 (SAS, Cary, North Carolina). RESULTS Among the 18,606 service members included in the analysis, 21% (N = 3,825) were cases and 79% (N = 14,781) were
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military TABLE I.
Demographic and Military Characteristics of Cases and Controls (N = 18,606) Opiate Dependence Status Diagnosis of Opiate Dependence and Abuse" (N = 3,825)
Characteristics Sex Female Male Education* No High School High School Some College Bachelor’s Degree >Master’s Degree Unknown Marital Status* Single Married Other'' Service Army Air Force Coast Guard Marines Navy Rank E-E4 E5-E9 0 1 -0 4 0 5 -0 9 Warrant Deployments' No Deployments 1 Deployment 2-3 Deployments >4 Deployments PTSD Diagnosis Yes-^ No*
No Diagnosis of Opiate Dependence and Abuse6 (N = 14,781)
n
%
n
%
524 3,301
14 86
2,337 12,444
16 84
40 3,207 225 125 68 160
1 84 6 3 2 4
92 10,946 878 1,900 556 409
1 74 6 13 3 3
1,999 1,651 160
52 44 4
8,103 6,276 383
55 43 2
2,201 532 105 402 585
57 14 3 11 15
4,886 3,348 427 2357 3763
33 23 3 16 26
2,826 831 137 18 13
74 21 3 1 1
8,714 3,806 1955 195 111
59 26 13 1 1
2,573 948 289 15
67 25 7 1
10,087 3,073 1,496 125
68 21 10 1
478 3,347
13 87
82 14,699
1 99
Diagnosis of opiate dependence and abuse (cases) includes all active duty service members serving between 2000 and 2008, having an incident diag nosis of opiate dependency occurring between 2000 and 2008 in any diag nostic positions during 1 inpatient or at least 2 separate outpatient visits occurring within 1 year of each other. 6No diagnosis of opiate dependence and abuse (age, date of accession into the military [+1 year], and active duty status on the date of the cases incident encounter matched controls) includes all active duty service members never diagnosed with any opiate drug abuse or dependency. '^M aster’s degree: soldiers who had a master’s or doctorate degree. ''Other: not married or single. 'Deployments: total number of deploy ments prior to case’s incident opiate diagnosis. ■''Yes: Soldier has a PTSD encounter prior to cases incident opiate diagnosis. 'No: Soldier “does not” has a PTSD encounter prior to cases incident opiate diagnosis. ’•’Variables have missing data.
controls. The majority of the study population was male (85%), service members in the U.S. Army (38%), ranked El to E4 (62%), and without a history of deployment (68%). Over half (54%) of the services members were single and the majority completed high school (76%) followed by col
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lege (11%) (Table I). Thirteen percent of cases compared to 1% of controls had a prior diagnosis of PTSD. After adjusting for sex, education, marital status, rank, and deployment history, the odds of having a prior diagnosis of PTSD was 28 (95% Cl: 21.24-37.78) times greater for ser vice members with opiate dependency or abuse when com pared to service members without opiate dependency or abuse controls. In the adjusted model, sex, level of education, marital status, branch of service, rank, and deployment were independently associated with having higher odds of opiate dependency or abuse. Male (aOR = 1.24, 95% Cl: 1.10-1.40) service members and those with no high school education (aOR 4.02, 95% Cl: 2.26-7.15), high school education (aOR = 2.47, 95% Cl: 1.65-3.68), or some college education (aOR = 2.11, 95% Cl: 1.38-3.21) had significantly greater odds of opiate dependency or abuse when compared to female service members and those with a Master’s or Doctorate degree, respectively. Service members who were not married or single (aOR = 1.55, 95% Cl: 1.23-1.95) had a higher odds of opiate abuse or dependence when compared to those who were mar ried. Soldiers in the Army (aOR = 2.13, 95% Cl: 1.66-2.73) had “higher” odds of opiate dependency or abuse and Sailors in the Navy (aOR = 0.76, 95% Cl: 0.58-0.98) had significantly “lower odds of opiate abuse or dependence when compared to service members in the Coast Guard. Service members ranked El to E4 (aOR = 10.99, 95% Cl: 5.55-21.73), E5 to E9 (aOR = 2.76, 95% Cl: 1.41-5.38), and 01 to 0 4 (aOR = 2.79, 95% Cl: 1.45-5.38) had significantly higher odds of opiate dependency or abuse when compared to service mem bers who were rank 05 to 09. Moreover, service members with no history of deployment (aOR = 2.74, 95% Cl: 1.435.10) or at least 1 deployment (aOR = 2.60, 95% Cl: 1.404.85) had a significantly higher odds of opiate dependency or abuse when compared to Soldiers with >4 deployments (Table II). D IS C U S S IO N
Although numerous studies17-19 have investigated the associ ation between PTSD and substance abuse, to our knowledge, this is the first investigation among U.S. military service members looking at whether individuals diagnosed with opi ate dependence and abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched con trols. In this analysis, service members with opiate depen dence or abuse diagnoses were 28 times more likely to have a prior diagnosis of PTSD compared to controls. Most recently, a study completed at the San Francisco Veterans Affairs Medical Center revealed that physicians were more likely to prescribe opiate medication to veterans with mental health diagnoses (e.g., depression, anxiety, PTSD) when compared to veterans who did not have a mental health diag nosis.-- Although these study populations are different, the findings underscore the importance of understanding the interrelatedness of these two conditions from a biological, clinical, and epidemiological perspective.
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Opiate-Related Dependence/Abuse and PTSD Among Active-Component U.S. Military TA B LE II. Conditional Logistic Regression Analysis for the Association of Post-Traumatic Stress Disorder With a Diagnosis of Opiate Dependence or Abuse Among Active Duty U.S. Military Service Members, 2001 to 2008 Characteristics Sex Female Male Education No High School High School Some College Bachelor’s Degree >Master’s Degree" Unknown Marital Status Single Married Other'’ Service Army Air Force Coast Guard Marines Navy Rank E1-E4 E5-E9 0 1 -0 4 0 5 -0 9 Warrant Deployments" No Deployments 1 Deployment 2-3 Deployments >4Deployments PTSD Diagnosis Yes1' No'
OR'
95% Cl
aOR*
95% Cl
ref 1.19
1.07-1.32
ref 1.24
— 1.10-1.40
6.51 4.31 3.12 0.73 ref 5.15
4.05-10.45 3.23-5.75 2 .2 1 -M I 0.52-1.01 — 3.67-7.24
4.02 2.47 2.11 0.70 ref 3.00
2.26-7.15 1.65-3.68 1.38-3.21 0.48-1.02 — 1.95-4.63
1.59 ref 0.95
1.29-1.90
1.00 ref 1.55
0.91-1.10 — 1.23-1.95
2.13 0.85 ref 0.78 0.76
1.66-2.73 0.66-1.12 — 0.60-1.02 0.58-0.98
1.09-5.46
10.99 2.76 2.79 ref 0.71
5.55-21.73 1.41-5.38 1.45-5.38 — 0.28-1.79
2.47 3.04 1.81 ref
1.42-4.29 1.75-5.29 1.04-3.17 —
2.74 2.60 1.34 ref
1.43-5.10 1.40-4.85 0.71-2.52 —
29.17 ref
22.38-38.02
28.32 ref
21.24-37.78 —
—
—
0.87-1.03
1.91 0.64 ref 0.72 0.64
1.53-2.38 0.51-0.81
27.82 6.57 2.61 ref 2.44
15.26-50.71 3.66-11.79 1.42—4.82
—
0.56-0.91 0.51-0.81
—
"Master’s or doctoral-level degree. '’Other: not married or single. ‘ Deployments: total number of deployments prior to case’s incident opiate diagnosis. dYes: Soldier has a PTSD encounter prior to cases incident opiate diagnosis. "No: Soldier does not has a PTSD encounter prior to cases inci dent opiate diagnosis. 'OR: odds ratio. ?aOR: adjusted odds ratio.
There are two models or pathways that explain the rela tionship between PTSD and substance abuse. 10 In the first model, PTSD precedes (and for an unknown reason contrib utes to) substance abuse. In the second, an individual who suffers from a substance abuse disorder (SUD) develops PTSD as a result of trauma sustained in the context of pro curement and use of that substance.”3'24 The first model, in which PTSD precedes the SUD, is more applicable to this investigation. This model supports the theory of self-medication in which an individual who suffers from PTSD symptoms (e.g., reexperiencing the traumatic event, avoidance, numb ing, and hyperarousal) uses illicit drugs or alcohol to alleviate these symptoms or prevent them from reoccurring.”5 More specifically, for individuals who are genetically predisposed to addiction ,26 having PTSD may increase the likelihood
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of developing opiate abuse or dependency based on patients’ self-report that opioids acutely improve symptoms related to PTSD .25 Among individuals with acute or chronic PTSD, there are a number of complex neurochemical events that occur in various regions of the brain and influence specific symptoms. Studies have shown that baseline noradrenergic functions increase in individuals with PTSD, which causes an elevation in the chemical norepinephrine (NE) .27 Elevations in the fight or flight chemical NE can cause panic attacks, insomnia, increased startle reflex, and hyperarousal. The level of NE can widely fluctuate depending on the strength of environmental stimuli.27 Along with an increase in NE activity, PTSD is associated with a continuous increase in dopaminergic activity through the release of dopamine, which preferentially targets the mesoprefrontal cortical areas and can induce generalized anxiety, panic attacks, hypervigilance, and exaggerated startle reflex.27 A third neurochemical elevated in individuals with PTSD is endogenous opiates that are released in times of stress.28 Endogenous opiates are secreted by the body as a counter mechanism (defensive coping) to alleviate symptoms of PTSD, creating a type of a physical and cerebral analge sia.28 A study in the journal, Pain, concluded that in the civil ian population, patients with a diagnosis of PTSD reported significantly higher subjective pain levels as compared to those without PTSD and that there may be a shared vulnerability pathway between PTSD and pain via the endogenous opioid neurotransmission systems.29 Higher levels of subjective pain sensitivity could lead to the prescribing of exogenous opiates (e.g., hydrocodone, oxycodone) by a treating physician. Exog enous opiates work to enhance the function of the endogenous opiates at the mu receptors, decrease the NE levels in the brain and shifts dopaminergic activity to the pleasure center of the brain. This combination counteracts the negative symptoms of PTSD, providing a sense of calmness and pleasure which may explain why individuals with PTSD self-medicate with exoge nous opiate medications.27 Preexisting psychiatric disorders can influence the development of opioid use disorders. The two aforementioned models do not take this into account because the military population is prescreened for psychiatric disorders and often disqualifies recruits for military service if they have a behavioral health condition that requires medica tion for treatment.24' 30 In the present model, service members who had one deployment or no history of deployment were significantly more likely to have a diagnosis of opiate dependency or abuse when compared to service members with four or more deployments. This may be explained by what Haley describes as the “healthy-warrior effect.” 31 The healthywarrior effect, which was derived from the healthy-worker effect, is a common bias present in occupational health stud ies to describe the reduction in morbidity and mortality among workers and the general population.3” The healthyworker effect assumes that individuals who work are rela tively healthier and more resilient than those in the general
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military
population who are unable to work. Following the Persian Gulf War, three studies were published33-^35 explaining the “healthy-Soldier effect,” which hypothesized that during pre-enlistment examination and basic training, unhealthy service members were removed from duty. Haley expounded on this hypothesis, purporting that deployed service mem bers were healthier than nondeployable service members dubbing this the healthy-warrior effect.31 This theory was reaffirmed among current Operation Enduring Freedom/ Operation Iraqi Freedom service members, finding that deployed U.S. Marines were significantly less likely to have ever had a psychiatric diagnosis compared to Marines with out a history of deployment.36 Soldiers with multiple deploy ments require the maintenance of a relatively high level of mental and physical health to remain deployable. Previous studies have reported on outcomes associated with Soldiers who have deployed.-- These findings suggest that although deployment is associated with an increased odds of opiate use, it is not the sole predictor for a Soldiers’ future diagnosis of opiate dependence or abuse. Therefore, other mental and physical risk factors must be considered. This study was not without limitations. First, it was not possible to ascertain whether a documented opiate diagnosis was for illicit drugs (either abuse or dependence of prescrip tion opiates that are not prescribed to the service member or use of illegal opioid type drugs such as heroin), prescription drugs (abuse or dependence of drugs that were prescribed by a physician for medicinal purposes to a service member), or both. This distinction should be explored in future analysis because recreational opiate abuse (illicit) differs from abuse related to physician-prescribed medications.37 For example, recreational abusers who become dependent on illicit drugs, or illegally obtained prescription opiates, are often secretive about their behavior and use these drugs to duplicate the sensation that is achieved from their initial “high” from the drug.37 Among these individuals, dependency develops over a short period as a result of the need for an increase in dosage.37 Conversely, individuals who become dependent on prescription opiates (nonillicit) usually come in contact with the medication(s) by a physician treating them for some form of physical pain.38 In these instances, prescription abuse (nonillicit) is less secretive and drug dependence progresses in a more subtle manner. However, if monitored appropri ately (e.g., initiation of a treatment plan), signs of abuse can be remedied more quickly by a supervising physician.38 Sec ond, information regarding prior history (before entry into the aimed services) or family history of SUDs was not available because the military does not have access to medical data for service members before their enrollment. Thus, there are likely some cases that had preexisting opioid dependence or abuse; diagnosed before development of PTSD, and should have been excluded from the study. Third, medical history of substance abuse (other than opiates) and other comorbid con ditions associated with PTSD39-41 were not accounted for in this analysis. It is not uncommon for service member with
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PTSD to use multiple substances during the course of the disease and suffer from other conditions.10 Finally, the prev alence of PTSD and opiate dependence or abuse in the study population may be artificially low due to undiagnosed PTSD among service members6 because of stigma associated with seeking behavioral health-related services.42,43 In view of these limitations, there are numerous strengths to this analysis. To our knowledge, this is the first and most comprehensive investigation among U.S. military service members across all five branches of service that examines the relationship between opiate dependency or abuse and prior diagnosis of PTSD. Moreover, this study will be among the first of two to unpack the temporal association (not dichotomy) between PTSD and opiate abuse and dependence. By using the entire active-component military population, selection bias was minimized by reducing the chance of hav ing disease-exposure groups that were differential, which could have occurred if only a sample of the population was used in the analysis. For instance, if using a sample, a greater proportion of cases with PTSD as compared to those without PTSD could have been unknowingly selected, which would bias the aOR away from the null. Unlike previous studies, where other factors were used as a proxy for opiate depen dency or abuse, this analysis included incident diagnoses of opiate dependency or abuse. In addition, among cases, the diagnosis of PTSD preceded the diagnosis of opiate depen dency or abuse, which further substantiates the supposition that individuals diagnosed with opiate dependence or abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched controls. Given the aforementioned data, clinicians should take a thorough patient history to include both past medical his tory and family history of SUD when prescribing opiate medications to service members with PTSD. For individuals who report a history of SUD, all alternative pain manage ment modalities (e.g., yoga, physical therapy, nonnarcotic medications) should be explored before prescribing opiate medications. If opiate medications prove necessary, service members should be closely monitored for signs of abuse and misuse. Historically, as a consequence of every major war, service members have reported subsequent problems related to men tal and behavioral health and substance use and abuse. As diagnoses for PTSD and opiate dependency and abuse con tinue to rise, improved awareness and attention needs to be placed on service members diagnosed with PTSD. More over, providers treating these service members need to practice due diligence when prescribing and recommending therapeu tic regimens. REFERENCES 1■ Riggs P: Non-medical use and abuse of commonly prescribed medica tions. Curr Med Res Opin 2008; 24(3): 869-77. 2. MMWR: Vital signs: overdoses of prescription opioid pain relievers— United States, 1999-2008. MMWR 2011; 60(43): 1487-92.
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component US. Military 3. National Institute of Health NIDA: Topics in Brief: Prescription drug abuse: the science of drug abuse and addiction, 2011. 4. Bray R. 2008 Department of Defense Survey of Health Related Behav iors Among Active Duty Military Personnel. Research Triangle Park, NC, RTI International 2009. 5. DMED: Defense Medical Epidemiology Database. Armed Forces Health Surveillance Center, 2011. 6. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL: Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Eng J Med 2004; 351(1): 13-22. 7. Hyams KC, Wignall FS, Roswell R: War syndromes and their evalua tion: from the U.S. Civil War to the Persian Gulf War. Ann Inter Med 1996; 125(5): 398-405. 8. MacDonald C, Chamberlain K, Long N, Flett R: Posttraumatic stress disorder and inteipersonal functioning in Vietnam War veterans: a mediational model. J Trauma Stress 1999; 12(4); 701-7. 9. Milliken CS, Auchterlonie JL, Hoge CW: Longitudinal assessment of mental health problems among active and reserve component soldiers returning from the Iraq war. JAMA 2007; 298(18): 2141—8. 10. Jacobsen LK, Southwick SM, Kosten TR: Substance use disorders in patients with posttraumatic stress disorder: a review of the literature. Am J Psychiatry 2001; 158(8): 1184-90. 11. Nazarian D KR. Frayne S: Posttraumatic stress disorder, substance use disorders, and medical comorbidity among returning U.S. veterans. J Trauma Stress 2012; 25: 220-5. 12. Papastavarou E, Farmakas A, Karayliannis G, Kotrotsiou E: CoMorbidity of post-traumatic-stress disorders and substance use disorder. Health Sci J 2011; 5(2). 13. Brown JM WJ, Bray RB. Hourani L: Postdeployment alcohol use. Mil Med 2012; 177(10): 1184. 14. Hoge CW AJ, Milliken CS: Mental health problems, use of mental health services, and attrition from military service after returning from deployment to Iraq or Afghanistan. JAMA 2006; 295: 1023-32. 15. Petrakis IL RR, Desai R: Substance use comorbidity among veterans with posttraumatic stress disorder and other psychiatric illness. Am J Addict 2011:20: 185-9. 16. Cottier LB, Compton WM III, Mager D, Spitznagel EL, Janca A: Post traumatic stress disorder among substance users from the general popu lation. Am J Psychiatry 1992; 149(5): 664-70. 17. Breslau N, Davis GC, Schultz LR: Posttraumatic stress disorder and the incidence of nicotine, alcohol, and other drug disorders in persons who have experienced trauma. Arch Gen Psychiatry 2003; 60(3): 289—94. 18. Chilcoat HD, Breslau N: Posttraumatic stress disorder and drug disorders: testing causal pathways. Arch Gen Psychiatry 1998; 55(10): 913-7. 19. Johnson SD, Striley C, Cottier LB: The association of substance use disorders with trauma exposure and PTSD among African American drug users. Addict Behav 2006; 31(11): 2063—73. 20. Rubertone MV BJ: The Defense Medical Surveillance System and the Department of Defense Serum Repository: glimpses of the future of public health surveillance. Am J Public Health 2002; 92(12): 1900-4. 21. US Army Homepage. 2013. Available at http://www.goarmy.com/ about/personnel.html; accessed August 13, 2013. 22. Seal KH, Shi Y, Cohen G, et al: Association of mental health disorders with prescription opioids and high-risk opioid use in US veterans of Iraq and Afghanistan. JAMA 2012; 307(9): 940-7. 23. Brady KT, Dansky BS, Sonne SC, Saladin ME: Posttraumatic stress disorder and cocaine dependence. Order of onset. Am J Addict 1998; 7(2): 128—35. 24. Villagonzalo KA, Dodd S, Ng F, Mihaly S, Langbein A, Berk M: The relationship between substance use and posttraumatic stress disorder
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in a methadone maintenance treatment program. Compr Psychiatry 2011; 52: 562-6. 25. Bremner JD, Southwick SM, Darnell A, Chamey DS: Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. Am J Psychiatry 1996; 153(3): 369-75. 26. Li CY, Zhou WZ, Zhang PW. Johnson C. Wei L, Uhl GR: Meta-analysis and genome-wide interpretation of genetic susceptibility to drug addic tion. BMC Genomics 2011; 12: 508. 27. Chamey DS. Deutch AY, Krystal JH, Southwick SM, Davis M: Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychi atry 1993; 50: 295-305. 28. Pitman RK, van der Kolk BA, Orr SP, Greenberg MS: Naloxone revers ible analgesic response to combat-related stimuli in post traumatic stress disorder. Arch General Psychiatry 1990; 47: 541-4. 29. Phifer J, Skelton K, Weiss T, et al: Pain symptomatology and pain medication use in civilian PTSD. Pain 2011; 152: 2233-40. 30. Robert Cardona, Elspeth CR: Psychological screening of recruits prior to accession in the US military. In: Recruit Medicine, Ed 1, pp 297309. Edited by DeKoning BL. Rockville, MD, Office of the Surgeon General, 2006. 31. Haley RW: Point: bias from the “healthy-warrior effect” and unequal follow-up in three government studies of health effects of the Gulf War. Am J Epidemiol 1998; 148(4): 31-23. 32. Wen CP, Tsai SP, Gibson RL: Anatomy of the healthy worker effect: a critical review. J Occup Med 1983; 25(4): 283-9. 33. Cowan DN, DeFraites RF. Gray GC, Goldenbaum MB. Wishik SM: The risk of birth defects among children of Persian Gulf War veterans. N Eng J Med 1997; 336(23): 1650-6. 34. Gray GC, Coate BD, Anderson CM, et al: The postwar hospitalization experience of U.S. veterans of the Persian Gulf War. N Eng J Med 1996; 335(20): 1505-13. 35. Kang HK, Bullman TA: Mortality among U.S. veterans of the Persian Gulf War. N Eng J Med 1996; 335(20): 1498-504. 36. Larson GE. Highfill-McRoy RM. Booth-Kewley S: Psychiatric diag noses in historic and contemporary military cohorts: combat deploy ment and the healthy warrior effect. Am J Epidemiol 2008; 167(11): 1269-76. 37. Katz NP AE, Adams EH, Chilcoat HS, et al: Challenges in the develop ment of prescription opioid abuse-defferent formulations. Clin J Pain 2007; 23(8): 648-60. 38. Fishbain DAM: Polypharmacy Treatment Approaches to the Psychiatric and Somatic Comorbidities Found in Patients with Chronic Pain. Am J Phys Med Rehabil 2005; 84(3): S56-S63. 39. Rand Corporation: Invisible Wounds of War: Psychological and Cogni tive Injuries, their Consequences, and Services to Assist Recovery. Santa Monica, CA. Rand Corporation, Center for Military Health Policy Research, 2008. 40. Hofmann SG, Litz BT, Weathers FW: Social anxiety, depression, and PTSD in Vietnam veterans. J Anxiety Disord 2003; 17(5): 573-82. 41. Reger ML, Poulos AM, Buen F, Giza CC, Hovda DA, Fanselow MS: Concussive brain injury enhances fear learning and excitatory processes in the amygdala. Biol Psychiatry 2012; 71(4): 335-43. 42. Command UAPH: White Paper: Stigma and related barriers to behav ioral health services among soldiers: lessons learned from epidemiolog ical consultation (EPICON) focus groups. In: BSHOP. Edited by BSHOP, 2011. 43. Kessler RC, Berglund PA, Bruce ML, et al: The prevalence and corre lates of untreated serious mental illness. Health Serv Res 2001; 36(6 Pt 1): 987-1007.
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Opiate-Related Dependence/Abuse and PTSD Exposure Among the Active-Component U.S. Military, 2001 to 2008 Clifton Dabbs, DO, MPH*; Eren Youmans Watkins, PhD, M PHf; David S. Fink, M PHf; Angelia Eick-Cost, PhD, ScM f, Amy M. Miilikan, MD, M PH f
ABSTRACT Background: Over the past 5 years, diagnoses for opiate abuse or dependency and post-traumatic stress disorder (PTSD) have increased across all U.S. military services. Moreover, in the United States, opiate prescription dependence and abuse has now surpassed all other illicit drugs of abuse with the exception of marijuana. Some research indicates that PTSD is predictive of substance dependence and abuse, while other research suggests that substance dependence and abuse may lead to events that trigger PTSD. This dichotomy has not been extensively explored within a military population. Methods: Using conditional multiple logistic regression analysis, a matched case-control study with 18,606 active-component U.S. military service members was conducted to examine the relationship between opiate dependence or abuse and PTSD. Results: Among the 18,606 service members included in the analysis, 21% were cases and 79% were controls. Thirteen percent of service members with substance dependence or abuse diagnosis had a prior PTSD diagnosis compared to 1% of controls. After, adjusting for sociodemographic and military characteristics, the odds of having a prior diagnosis of PTSD was 28 (95% Cl: 21.24-37.78) times greater for service members with opiate abuse/dependency compared to controls. Conclusion: These findings suggest active duty military personnel diagnosed with PTSD should be closely monitored to reduce the likelihood of future morbidity because of opiate dependence or abuse.
INTRODUCTION Over the last decade, opiate dependence, a medical diagnosis characterized by an individual’s inability to stop using opi oids, and opioid abuse, compulsive use of opioids that pose harm to a person’s health or social functioning, have been a rising public health problem .1 In the United States, the annual number of deaths related to prescription opioids now exceeds the number of deaths related to heroin and cocaine com bined.- From 1991 to 2010, the United States experienced a three-fold increase in prescriptions for opioid analgesics (75.5-209.5 million) and prescription opiate dependence and abuse has now surpassed all other illicit drugs of abuse with the exception of marijuana.3 A similar trend is prevalent across U.S. military branches.4 Between 2002 and 2008, pre scription opioid dependence and abuse among Department of Defense service members rose from 1% to 10%.5 More spe cifically, from 2007 to 2010, there was a 700% increase in the rate of opioid dependence and abuse among Soldiers in the U.S. Army.5
*Department of Preventive Medicine, Walter Reed Army Institute of Research, 621 Derringer, Bel Air. MD 21015. tArmy Institute of Public Health, Behavioral and Social Health Out comes Program, 5158 Blackhawk Road, Building 1570, Aberdeen Proving Ground, MD 21010. fArmed Forces Health Surveillance Center, 503 Robert Grant Avenue, Silver Spring, MD 21090. The views expressed in this article are those of the authors and do not reflect official policy or position of the Department of the Army, the Depart ment of Defense, the U.S. Government or any of the institutional affiliations listed. None of these authors have any conflicts of interest to declare, doi: 10.7205/MILMED-D-14-00012
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Historically, behavioral health problems and psychiatric illnesses have been an issue for service members returning from war.6 } Most recently, 1 in 8 service members returning from Operation Enduring Freedom or Operation Iraqi Free dom have screened positive for post-traumatic stress disorder (PTSD).6 Almost parallel to the increase in the diagnosis of PTSD across the services was the rise in opioid dependence and abuse (Fig. 1 and Fig. 2).5 Although some research indi cates that PTSD is predictive of substance dependence and abuse, 11-15 other research suggests that substance depen dence and abuse increases the likelihood of exposure to trauma, which may lead to PTSD .16 This dichotomy is not fully understood and has not been extensively explored within the military population. Among studies that have been conducted to explore the nexus between PTSD and sub stance, most have been among military veterans.17-19 The objective of this study was to determine whether individuals diagnosed with opiate dependence and abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched controls within a large military population. Moreover, this study will be among the first to unpack the temporal association (not dichotomy) between PTSD and opiate abuse and dependence, which will have significant implications for the identification of prevention and treatment of these disorders.
METHODS Sources of Data This study was conducted using administrative data from the Department of Defense Defense Medical Surveillance System (DMSS) database."0 DMSS contains information on service
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military medical diagnosis for PTSD, was defined as an inpatient or outpatient diagnosis with PTSD (ICD-9: 309.81) in any diag nostic position before the opiate dependency or abuse diagnosis. Military characteristics included branch of service, rank (Enlisted [E] 1 through 9, Commissioned Officer [O] 1 through 9 and Warrant Officers) and deployment history. Much like employees at a company, Enlisted Soldiers perform specific job functions and have the knowledge that ensures the suc cess of their unit’s current mission within the Army. An Enlisted Soldiers rank can range from Private (El) to Ser geant Major of the Army (E9). Commissioned Officers are FIGURE 1. Rate of post-traumatic stress disorder diagnosed among U.S. responsible for completing demanding missions while ensur military service members, 2001 to 2010.5 ing the welfare, morale, and professional development of the Soldiers entrusted to them. An Officer’s rank can range from Second Lieutenant (01) through General (09). Warrant Offi cers are highly specialized experts and trainers in their career fields. Warrant Officers remain single-specialty Officers with career tracks that progress within their field, unlike their Commissioned Officer counterparts who focus on increased levels of command and staff duty positions. Warrant Officers rank can range from Warrant Office 1 through Chief Warrant Officer 5.21 Rank was categorized as El to E4, E5 to E9, Ol to 04, and Warrant Officers. Deployment history was defined as the total number (categorical variable) of deployments before a case’s incident opiate diagnosis. Sociodemographic characteristics included sex, education, FIGURE 2. Rate of opiate dependence diagnosed among U.S. military and marital status. Service members with a high school service members, 2001 to 2010.5 diploma or general education diploma were classified as hav ing a high school education. In addition, service members member’s sociodemographic characteristics, deployment infor with any type of postbaccalaureate degree (e.g., master’s mation, and medical records. Medical data (using International degree, PhD, medical degree) were collapsed into a single Classification of Disease, Ninth Revision (ICD-9-CM) codes) category (> master’s degree). Time-varying covariates were in DMSS are generated from billing code data on inpatient and provided at the time of the case’s diagnosis date. Five hun outpatient clinical visits occurring at military treatment facili dred sixty-nine service members with missing information on ties and outsourced care. The Walter Reed Army Institute of education were classified as Unknown. Marital status was Research Institutional Review Board approved this study and categorized as married, single, and other. A total of 18,606 assigned protocol no. 1712. service members were included in the analysis. Study Population A nested case-control study was conducted among activecomponent U.S. service members from the five branches (Air Force, Army, Coast Guard, Marines, and Navy) of ser vice. Cases were defined as service members, who served at any time from 2001 to 2008 and had a first-time diagnosis of opiate dependency (ICD-9: 304.00, 304.01, 304.02, 304.70, 304.71, or 304.72) or opiate abuse (ICD-9:305.50, 305.51, or 305.52) that occurred from 2001 to 2008 in any diagnostic position during one inpatient or at least two separate outpatient visits within a 365-day period. Controls were defined as active duty service members who did not have a diagnosis for opiate drug dependency or abuse within the Military Health System database. Each case was matched with up to four controls by date of birth (±1 year), date of accession into the military (±1 year), and active-component status on the date of the case’s first opiate (incident) diagnosis. The exposure of interest, a
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Statistical Analyses Frequency distributions were examined for all of socio demographic and military characteristics and percentages were used to describe categorical variables. Conditional multiple logistic regression modeling was conducted to determine the association between an incident diagnosis of opiate depen dency or abuse and PTSD while controlling for the aforemen tioned sociodemographic and military characteristics known to be associated with PTSD and opiate dependency or abuse. Adjusted odds ratios (aOR) and 95% confidence intervals (95% Cl) are reported. Data analysis was performed using SAS v. 9.2 (SAS, Cary, North Carolina). RESULTS Among the 18,606 service members included in the analysis, 21% (N = 3,825) were cases and 79% (N = 14,781) were
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military TABLE I.
Demographic and Military Characteristics of Cases and Controls (N = 18,606) Opiate Dependence Status Diagnosis of Opiate Dependence and Abuse" (N = 3,825)
Characteristics Sex Female Male Education* No High School High School Some College Bachelor’s Degree >Master’s Degree Unknown Marital Status* Single Married Other'' Service Army Air Force Coast Guard Marines Navy Rank E-E4 E5-E9 0 1 -0 4 0 5 -0 9 Warrant Deployments' No Deployments 1 Deployment 2-3 Deployments >4 Deployments PTSD Diagnosis Yes-^ No*
No Diagnosis of Opiate Dependence and Abuse6 (N = 14,781)
n
%
n
%
524 3,301
14 86
2,337 12,444
16 84
40 3,207 225 125 68 160
1 84 6 3 2 4
92 10,946 878 1,900 556 409
1 74 6 13 3 3
1,999 1,651 160
52 44 4
8,103 6,276 383
55 43 2
2,201 532 105 402 585
57 14 3 11 15
4,886 3,348 427 2357 3763
33 23 3 16 26
2,826 831 137 18 13
74 21 3 1 1
8,714 3,806 1955 195 111
59 26 13 1 1
2,573 948 289 15
67 25 7 1
10,087 3,073 1,496 125
68 21 10 1
478 3,347
13 87
82 14,699
1 99
Diagnosis of opiate dependence and abuse (cases) includes all active duty service members serving between 2000 and 2008, having an incident diag nosis of opiate dependency occurring between 2000 and 2008 in any diag nostic positions during 1 inpatient or at least 2 separate outpatient visits occurring within 1 year of each other. 6No diagnosis of opiate dependence and abuse (age, date of accession into the military [+1 year], and active duty status on the date of the cases incident encounter matched controls) includes all active duty service members never diagnosed with any opiate drug abuse or dependency. '^M aster’s degree: soldiers who had a master’s or doctorate degree. ''Other: not married or single. 'Deployments: total number of deploy ments prior to case’s incident opiate diagnosis. ■''Yes: Soldier has a PTSD encounter prior to cases incident opiate diagnosis. 'No: Soldier “does not” has a PTSD encounter prior to cases incident opiate diagnosis. ’•’Variables have missing data.
controls. The majority of the study population was male (85%), service members in the U.S. Army (38%), ranked El to E4 (62%), and without a history of deployment (68%). Over half (54%) of the services members were single and the majority completed high school (76%) followed by col
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lege (11%) (Table I). Thirteen percent of cases compared to 1% of controls had a prior diagnosis of PTSD. After adjusting for sex, education, marital status, rank, and deployment history, the odds of having a prior diagnosis of PTSD was 28 (95% Cl: 21.24-37.78) times greater for ser vice members with opiate dependency or abuse when com pared to service members without opiate dependency or abuse controls. In the adjusted model, sex, level of education, marital status, branch of service, rank, and deployment were independently associated with having higher odds of opiate dependency or abuse. Male (aOR = 1.24, 95% Cl: 1.10-1.40) service members and those with no high school education (aOR 4.02, 95% Cl: 2.26-7.15), high school education (aOR = 2.47, 95% Cl: 1.65-3.68), or some college education (aOR = 2.11, 95% Cl: 1.38-3.21) had significantly greater odds of opiate dependency or abuse when compared to female service members and those with a Master’s or Doctorate degree, respectively. Service members who were not married or single (aOR = 1.55, 95% Cl: 1.23-1.95) had a higher odds of opiate abuse or dependence when compared to those who were mar ried. Soldiers in the Army (aOR = 2.13, 95% Cl: 1.66-2.73) had “higher” odds of opiate dependency or abuse and Sailors in the Navy (aOR = 0.76, 95% Cl: 0.58-0.98) had significantly “lower odds of opiate abuse or dependence when compared to service members in the Coast Guard. Service members ranked El to E4 (aOR = 10.99, 95% Cl: 5.55-21.73), E5 to E9 (aOR = 2.76, 95% Cl: 1.41-5.38), and 01 to 0 4 (aOR = 2.79, 95% Cl: 1.45-5.38) had significantly higher odds of opiate dependency or abuse when compared to service mem bers who were rank 05 to 09. Moreover, service members with no history of deployment (aOR = 2.74, 95% Cl: 1.435.10) or at least 1 deployment (aOR = 2.60, 95% Cl: 1.404.85) had a significantly higher odds of opiate dependency or abuse when compared to Soldiers with >4 deployments (Table II). D IS C U S S IO N
Although numerous studies17-19 have investigated the associ ation between PTSD and substance abuse, to our knowledge, this is the first investigation among U.S. military service members looking at whether individuals diagnosed with opi ate dependence and abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched con trols. In this analysis, service members with opiate depen dence or abuse diagnoses were 28 times more likely to have a prior diagnosis of PTSD compared to controls. Most recently, a study completed at the San Francisco Veterans Affairs Medical Center revealed that physicians were more likely to prescribe opiate medication to veterans with mental health diagnoses (e.g., depression, anxiety, PTSD) when compared to veterans who did not have a mental health diag nosis.-- Although these study populations are different, the findings underscore the importance of understanding the interrelatedness of these two conditions from a biological, clinical, and epidemiological perspective.
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Opiate-Related Dependence/Abuse and PTSD Among Active-Component U.S. Military TA B LE II. Conditional Logistic Regression Analysis for the Association of Post-Traumatic Stress Disorder With a Diagnosis of Opiate Dependence or Abuse Among Active Duty U.S. Military Service Members, 2001 to 2008 Characteristics Sex Female Male Education No High School High School Some College Bachelor’s Degree >Master’s Degree" Unknown Marital Status Single Married Other'’ Service Army Air Force Coast Guard Marines Navy Rank E1-E4 E5-E9 0 1 -0 4 0 5 -0 9 Warrant Deployments" No Deployments 1 Deployment 2-3 Deployments >4Deployments PTSD Diagnosis Yes1' No'
OR'
95% Cl
aOR*
95% Cl
ref 1.19
1.07-1.32
ref 1.24
— 1.10-1.40
6.51 4.31 3.12 0.73 ref 5.15
4.05-10.45 3.23-5.75 2 .2 1 -M I 0.52-1.01 — 3.67-7.24
4.02 2.47 2.11 0.70 ref 3.00
2.26-7.15 1.65-3.68 1.38-3.21 0.48-1.02 — 1.95-4.63
1.59 ref 0.95
1.29-1.90
1.00 ref 1.55
0.91-1.10 — 1.23-1.95
2.13 0.85 ref 0.78 0.76
1.66-2.73 0.66-1.12 — 0.60-1.02 0.58-0.98
1.09-5.46
10.99 2.76 2.79 ref 0.71
5.55-21.73 1.41-5.38 1.45-5.38 — 0.28-1.79
2.47 3.04 1.81 ref
1.42-4.29 1.75-5.29 1.04-3.17 —
2.74 2.60 1.34 ref
1.43-5.10 1.40-4.85 0.71-2.52 —
29.17 ref
22.38-38.02
28.32 ref
21.24-37.78 —
—
—
0.87-1.03
1.91 0.64 ref 0.72 0.64
1.53-2.38 0.51-0.81
27.82 6.57 2.61 ref 2.44
15.26-50.71 3.66-11.79 1.42—4.82
—
0.56-0.91 0.51-0.81
—
"Master’s or doctoral-level degree. '’Other: not married or single. ‘ Deployments: total number of deployments prior to case’s incident opiate diagnosis. dYes: Soldier has a PTSD encounter prior to cases incident opiate diagnosis. "No: Soldier does not has a PTSD encounter prior to cases inci dent opiate diagnosis. 'OR: odds ratio. ?aOR: adjusted odds ratio.
There are two models or pathways that explain the rela tionship between PTSD and substance abuse. 10 In the first model, PTSD precedes (and for an unknown reason contrib utes to) substance abuse. In the second, an individual who suffers from a substance abuse disorder (SUD) develops PTSD as a result of trauma sustained in the context of pro curement and use of that substance.”3'24 The first model, in which PTSD precedes the SUD, is more applicable to this investigation. This model supports the theory of self-medication in which an individual who suffers from PTSD symptoms (e.g., reexperiencing the traumatic event, avoidance, numb ing, and hyperarousal) uses illicit drugs or alcohol to alleviate these symptoms or prevent them from reoccurring.”5 More specifically, for individuals who are genetically predisposed to addiction ,26 having PTSD may increase the likelihood
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of developing opiate abuse or dependency based on patients’ self-report that opioids acutely improve symptoms related to PTSD .25 Among individuals with acute or chronic PTSD, there are a number of complex neurochemical events that occur in various regions of the brain and influence specific symptoms. Studies have shown that baseline noradrenergic functions increase in individuals with PTSD, which causes an elevation in the chemical norepinephrine (NE) .27 Elevations in the fight or flight chemical NE can cause panic attacks, insomnia, increased startle reflex, and hyperarousal. The level of NE can widely fluctuate depending on the strength of environmental stimuli.27 Along with an increase in NE activity, PTSD is associated with a continuous increase in dopaminergic activity through the release of dopamine, which preferentially targets the mesoprefrontal cortical areas and can induce generalized anxiety, panic attacks, hypervigilance, and exaggerated startle reflex.27 A third neurochemical elevated in individuals with PTSD is endogenous opiates that are released in times of stress.28 Endogenous opiates are secreted by the body as a counter mechanism (defensive coping) to alleviate symptoms of PTSD, creating a type of a physical and cerebral analge sia.28 A study in the journal, Pain, concluded that in the civil ian population, patients with a diagnosis of PTSD reported significantly higher subjective pain levels as compared to those without PTSD and that there may be a shared vulnerability pathway between PTSD and pain via the endogenous opioid neurotransmission systems.29 Higher levels of subjective pain sensitivity could lead to the prescribing of exogenous opiates (e.g., hydrocodone, oxycodone) by a treating physician. Exog enous opiates work to enhance the function of the endogenous opiates at the mu receptors, decrease the NE levels in the brain and shifts dopaminergic activity to the pleasure center of the brain. This combination counteracts the negative symptoms of PTSD, providing a sense of calmness and pleasure which may explain why individuals with PTSD self-medicate with exoge nous opiate medications.27 Preexisting psychiatric disorders can influence the development of opioid use disorders. The two aforementioned models do not take this into account because the military population is prescreened for psychiatric disorders and often disqualifies recruits for military service if they have a behavioral health condition that requires medica tion for treatment.24' 30 In the present model, service members who had one deployment or no history of deployment were significantly more likely to have a diagnosis of opiate dependency or abuse when compared to service members with four or more deployments. This may be explained by what Haley describes as the “healthy-warrior effect.” 31 The healthywarrior effect, which was derived from the healthy-worker effect, is a common bias present in occupational health stud ies to describe the reduction in morbidity and mortality among workers and the general population.3” The healthyworker effect assumes that individuals who work are rela tively healthier and more resilient than those in the general
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Opiate-Related Dependence!Abuse and PTSD Among Active-Component U.S. Military
population who are unable to work. Following the Persian Gulf War, three studies were published33-^35 explaining the “healthy-Soldier effect,” which hypothesized that during pre-enlistment examination and basic training, unhealthy service members were removed from duty. Haley expounded on this hypothesis, purporting that deployed service mem bers were healthier than nondeployable service members dubbing this the healthy-warrior effect.31 This theory was reaffirmed among current Operation Enduring Freedom/ Operation Iraqi Freedom service members, finding that deployed U.S. Marines were significantly less likely to have ever had a psychiatric diagnosis compared to Marines with out a history of deployment.36 Soldiers with multiple deploy ments require the maintenance of a relatively high level of mental and physical health to remain deployable. Previous studies have reported on outcomes associated with Soldiers who have deployed.-- These findings suggest that although deployment is associated with an increased odds of opiate use, it is not the sole predictor for a Soldiers’ future diagnosis of opiate dependence or abuse. Therefore, other mental and physical risk factors must be considered. This study was not without limitations. First, it was not possible to ascertain whether a documented opiate diagnosis was for illicit drugs (either abuse or dependence of prescrip tion opiates that are not prescribed to the service member or use of illegal opioid type drugs such as heroin), prescription drugs (abuse or dependence of drugs that were prescribed by a physician for medicinal purposes to a service member), or both. This distinction should be explored in future analysis because recreational opiate abuse (illicit) differs from abuse related to physician-prescribed medications.37 For example, recreational abusers who become dependent on illicit drugs, or illegally obtained prescription opiates, are often secretive about their behavior and use these drugs to duplicate the sensation that is achieved from their initial “high” from the drug.37 Among these individuals, dependency develops over a short period as a result of the need for an increase in dosage.37 Conversely, individuals who become dependent on prescription opiates (nonillicit) usually come in contact with the medication(s) by a physician treating them for some form of physical pain.38 In these instances, prescription abuse (nonillicit) is less secretive and drug dependence progresses in a more subtle manner. However, if monitored appropri ately (e.g., initiation of a treatment plan), signs of abuse can be remedied more quickly by a supervising physician.38 Sec ond, information regarding prior history (before entry into the aimed services) or family history of SUDs was not available because the military does not have access to medical data for service members before their enrollment. Thus, there are likely some cases that had preexisting opioid dependence or abuse; diagnosed before development of PTSD, and should have been excluded from the study. Third, medical history of substance abuse (other than opiates) and other comorbid con ditions associated with PTSD39-41 were not accounted for in this analysis. It is not uncommon for service member with
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PTSD to use multiple substances during the course of the disease and suffer from other conditions.10 Finally, the prev alence of PTSD and opiate dependence or abuse in the study population may be artificially low due to undiagnosed PTSD among service members6 because of stigma associated with seeking behavioral health-related services.42,43 In view of these limitations, there are numerous strengths to this analysis. To our knowledge, this is the first and most comprehensive investigation among U.S. military service members across all five branches of service that examines the relationship between opiate dependency or abuse and prior diagnosis of PTSD. Moreover, this study will be among the first of two to unpack the temporal association (not dichotomy) between PTSD and opiate abuse and dependence. By using the entire active-component military population, selection bias was minimized by reducing the chance of hav ing disease-exposure groups that were differential, which could have occurred if only a sample of the population was used in the analysis. For instance, if using a sample, a greater proportion of cases with PTSD as compared to those without PTSD could have been unknowingly selected, which would bias the aOR away from the null. Unlike previous studies, where other factors were used as a proxy for opiate depen dency or abuse, this analysis included incident diagnoses of opiate dependency or abuse. In addition, among cases, the diagnosis of PTSD preceded the diagnosis of opiate depen dency or abuse, which further substantiates the supposition that individuals diagnosed with opiate dependence or abuse are at increased odds of having a prior medical diagnosis for PTSD compared to matched controls. Given the aforementioned data, clinicians should take a thorough patient history to include both past medical his tory and family history of SUD when prescribing opiate medications to service members with PTSD. For individuals who report a history of SUD, all alternative pain manage ment modalities (e.g., yoga, physical therapy, nonnarcotic medications) should be explored before prescribing opiate medications. If opiate medications prove necessary, service members should be closely monitored for signs of abuse and misuse. Historically, as a consequence of every major war, service members have reported subsequent problems related to men tal and behavioral health and substance use and abuse. As diagnoses for PTSD and opiate dependency and abuse con tinue to rise, improved awareness and attention needs to be placed on service members diagnosed with PTSD. More over, providers treating these service members need to practice due diligence when prescribing and recommending therapeu tic regimens. REFERENCES 1■ Riggs P: Non-medical use and abuse of commonly prescribed medica tions. Curr Med Res Opin 2008; 24(3): 869-77. 2. MMWR: Vital signs: overdoses of prescription opioid pain relievers— United States, 1999-2008. MMWR 2011; 60(43): 1487-92.
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