Mental Health

1. Anxiety & Depression among Pain Patients are Associated with
Higher Pain Impairment, Increased Utilization and Poorer Health
Joseph A. Boscarino, PhD, MPH, Center Health Research
Stuart N. Hoffman, DO, Department of Neurology
Glenn S. Gerhard, MD, Weis Center
John J. Han, MD, Department of Anesthesiology
Margaret R. Rukstalis, MD, Center for Health Research
Porat M. Erlich, PhD, MPH Center for Health Research
Walter F. Stewart, PhD, MPH, Center for Health Research
Geisinger Clinic
Danville, PA
18th HMORN Conference
May 1, 2012 (Session B7)
HMORN Presentation 4-24-12.ppt

2. Funding
 Study funding for this research was provided by the
Geisinger Clinic Research Fund (Grant No. TRA-015).
Joseph A. Boscarino, PhD, MPH was the study PI.
 There are no conflicts of interest associated with his
research.

3. Past Month Nonmedical Use of Psychotherapeutic Drugs
among Persons Aged 12 or Older in US: 2002-2010
National Survey on Drug Use and Health, SAMHSA, 2011.

4. Specific Drug Associated with Initiation of Illicit Drug Use among
Illicit Drug Initiates Aged 12 or Older in US in the Past Year
National Survey on Drug Use and Health, SAMHSA, 2011.

5. Objective
 Research on opioid dependence is difficult, given
challenges to subject recruitment & measurement.
 We tested a research design by studying
prescription opioid use among outpatients at
Geisinger Clinic, Danville, PA.
 Objective was to assess the risk of addiction
among outpatients in a medical setting.

7. Method
 Cross-sectional study implemented among Geisinger
Clinic’s outpatients.
 Patients selected for diagnostic interviews if had 5+
prescription opioid orders for non-cancer pain in prior
12 months.
 Opioid dependence was based on the Diagnostic and
Statistical Manual of Mental Disorder - IV (DSM-IV).

8. DSM-IV Criteria
Opioid-related disorders:
305.50 - Abuse
304.00 - Dependence
292.84 - Induced mood disorder
292.11 - Induced psychotic disorder, with delusions
292.12 - Induced psychotic disorder, with
hallucinations
292.89 - Intoxication
292.81 - Intoxication delirium
292.9 - Related disorder NOS
292.0 - Withdrawal
DSM-IV Definition of Drug Dependence: Psychological and/or physical dependence
on a drug resulting from the use of that drug on a periodic or continuous basis. This
dependence is characterized by tolerance, withdrawal, and loss of control symptoms
related to drug taking and by psychosocial impairments. The individual who uses the
drug feels unable to function without the drug.

9. Method (cont’d)
 A Composite International Diagnostic Interview (CIDI)
was used to obtain data on addiction & mental health
status; also used other DSM-IV scales.
 Data collected on exposure to psychological
trauma, post-traumatic stress disorder (PTSD) &
other disorders.
 705 patients completed the survey; 505 of patients
(72%) provided DNA for genotyping and completed
the NEO Five-Factor Inventory.
 Data also gathered on demographics factors.
 EHR data also obtained.

10. Study Assessments
 Prescription opioid dependence (POD)
 Major depression (MD)
 Generalized anxiety disorder (GAD)
 Post-traumatic stress disorder (PTSD)
 Alcohol dependence (AD)
 Illicit drug dependence/abuse
 Childhood abuse/neglect
 Antisocial personality
 Trauma exposure history

11. Sample design
2459 adult patients
– 9 primary care & 3 specialty clinics
– ≥4 prescriptions 86 not contacted (study quota met)
– not cancer-related
– July 2006 – June 2007
983 not reachable or not qualified
– Institutionalized (nursing home, correctional
facility, mental institution, etc.)
– Incapable of answering questions
– Language barrier
2373 attempted contact (mail/phone)
– Denied taking medications
– Deceased
– Disconnected phone
– Busy signal/answering machine
– Business/wrong number
1390 actually contacted (8/07–11/08) 685 Not interested/declined study
705 consented & completed interview The mean age of patients was 55
years of age (SD=13.4) and 60.9%
(95% C.I. = 55.9-65.7) were female.
505 genotyped

12. World Health Organization
Composite International
Diagnostic Interview (CIDI)
Staff Certification and
Training are Important

13. Prevalence of Opioid Dependence*
Lifetime Drug No Lifetime
Dependence Measures Total Sample Dependence Dependence
Percent 95% C.I. (N) Percent 95% C.I. (N) Percent (N)
Lifetime Opioid Depend.
% Yes 35.1 30.6-39.8 (251) 100.0 --- (251) --- ---
% No --- --- --- 100.0 (454)
64.9 60.3-69.4 (454)
Current Opioid Depend.
% Yes 72.4 67.3-77.0 (181) 0.0 (0)
25.4 21.7-29.5 (181)
% No 27.6 23.0-32.7 (70) 100.0 (454)
74.6 70.5-78.3 (524)
*Based on DSM-IV criteria.
Boscarino, et al. Risk factors for drug dependence among outpatients on opioid
therapy in a large US healthcare system. Addiction. 2010; 105 (10): 1776-1782.

14. Lifetime DSM-5 Opioid-use Disorder vs. Lifetime DSM-4 Opioid Dependence
(tolerance & withdrawal dropped, craving added, abuse added, except legal probs)
DSM-5 Opioid-use DSM-5 Opioid-use Total DSM-4 Opioid
Disorder not Present Disorder Present Dependence
Diagnostic Criteria Used*
% 95% CI (n) % 95% CI (n) % 95% CI (n)
DSM-4 Opioid Depend not Pres. 94.9 92.2-96.7 (436) 7.7 4.3- 13.4 (18) 64.5 59.8-68.9 (454)
DSM-4 Opioid Depend Pres. 5.1 3.3-7.8 (23) 92.3 86.6-95.7 (228) 35.5 31.1-40.2 (251)
Total DSM-5 Opioid-use Disorder 65.1 60.5-69.5 (459) 34.9 30.5-39.5 (246) 100.0 -- -- (705)
*Kappa = 0.873, p < 0.0001 for DSM-4 vs. DSM-5.
Boscarino et al. Prevalence of prescription opioid-use disorder among chronic pain
patients: Comparison of the DSM-5 vs. DSM-4 criteria. J Addict Dis. 2011; 30: 185-194.

15. Why are DSM-4 and DSM-5
Results the Same?
1. Cases that would have been excluded under DSM-5
by elimination of withdrawal and tolerance are now
included by addition of the drug abuse and craving.
2. Also due to the retention of “loss of control” symptoms
in DSM-5, because those with withdrawal and
tolerance under DSM-4 also have loss of control
symptoms.
Boscarino et al. Prevalence of prescription opioid-use disorder among chronic pain
patients: Comparison of the DSM-5 vs. DSM-4 criteria. J Addict Dis. 2011; 30: 185-194.

16. Opioid Dependence by Select Predictors
Lifetime No Lifetime
Total Sample Drug Drug
Study Predictors Percent (N) Dependence Dependence
Percent (N) Percent (N)
Lifetime Opioid Drug Abuse
% Yes 12.3 (88) 31.8 (79) 1.9 (9)***
% No 87.7 (617) 98.1 (445)
68.3 (172)
Severity Opioid Dependence
% High 15.1 (108) 30.4 (77) 6.8 (31)***
% Not High 84.9 (597) 93.2 (423)
69.6 (174)
Lifetime Alcohol Dependence
% Yes 9.7 (68) 14.3 (36) 7.1 (32)**
% No 90.3 (637) 92.9 (442)
85.7 (215)
Lifetime Tobacco Dependence
% Yes 36.3 (251) 41.8 (103) 33.4 (148)***
% No 63.7 (454) 66.6 (306)
58.2 (148)
Lifetime Posttraumatic Stress
** p<0.01 % Yes 13.1 (97) 8.7 (42)***
21.3 (55)
*** p<0.001
** p<0.01 % No 86.9 (608) 91.3 (412)
78.7 (196)
*** p<0.001

17. Opioid Dependence by Select Predictors (cont’d)
Lifetime No Lifetime Drug
Study Predictors Total Sample Drug Dependence Dependence
Percent (N) Percent (N) Percent (N)
History Childhood Neglect
% High 24.6 (178) 33.0 (84) 20.1 (94)**
% Not High 75.4 (527) 79.9 (360)
67.0 (167)
History Exposure to Psych Trauma
% High 22.5 (161) 31.8 (80) 17.5 (81)***
% Not High 77.5 (544) 82.5 (373)
68.2 (171)
History Illicit Drug Use
% Yes 38.1 (273) 50.3 (127) 31.5 (146)***
% No 61.9 (432) 68.5 (308)
49.7 (124)
History Substance Abuse Treat.
% Yes 21.8 (153) 36.4 (90) 13.9 (63)***
% No 78.2 (552) 86.1 (391)
63.6 (161)
** p<0.01 History Anti-Social Personality
% Yes 23.3 (167) 32.7 (83) 18.3 (84)***
% No 76.7 (538) 81.7 (370)
** p<0.01 67.3 (168)
(N =) (705) (251) (454)
*** p<0.001

18. Pain & Prescription Opioid
Dependence are Associated
 Current pain scores on Brief Pain Inventory
correlated with opioid dependence symptoms
(r ~ 0.20) (p<0.001)
 32% of those with current opioid dependence
report high 7-day pain levels vs. 18% w/o
dependence (p<0.001)
 73% of those with current opioid dependence
report high pain functional impairment vs. 55%
w/o dependence (p<0.001)

19. Logistic Regression Results Predicting
Drug Dependence*
Model 1: Model 2:
Lifetime Opioid Dependence Current Opioid Dependence
Best Predictor Variables OR 95% CI p-value OR 95% CI p-value
Less than 65 Years Old 2.70 1.76-4.15 <0.001 2.24 1.37-3.64 0.004
Reported Pain Interferes with Life/work 2.20 1.50-3.23 0.001 1.74 1.13-2.66 0.016
History of Opioid Abuse 14.84 6.29-34.99 <0.001 3.90 1.46-10.40 0.011
History of High Addiction Severity 2.61 1.56-4.37 0.002 1.93 1.40-2.66 0.001
High Number Opioid Orders in past 3 Yrs 1.89 1.34-2.66 0.002 _ _ _
History of Major Depression -- -- -- 1.37 1.16-1.63 0.002
Currently on Psychotropic Medications -- -- -- 1.61 1.11-2.34 0.017
*Boscarino, et al. Risk factors for drug dependence among outpatients on opioid
therapy in a large US healthcare system. Addiction. 2010; 105 (10): 1776-1782.

20. Lifetime Prevalence of
Mental Disorders in Study
 POD = 37% (95% CI = 33-41%)
 PTSD = 15% (95% CI = 12-18%)
 GAD = 13% (95% CI = 11-17%)
 MD = 38% (95% CI = 34-42%)
POD = Prescription opioid dependence; PTSD = Posttraumatic
stress disorder; GAD = Generalized anxiety disorder; MD =
Major depression.

21. Patient Health Statistics
 20+ outpatient visits past year = 16%
 5+ hospitalizations past 5 years = 17%
 Rate health status poor = 19%
 Current pain interferes with life = 21%
 Ever treated for substance abuse = 22%
 Ever suicidal thoughts = 26%
 History of childhood neglect = 25%
 Ever used illicit drugs = 38%

22. Anxiety Associated with*
 Higher pain impairment (OR=2.0, p=0.01)
 Higher service utilization (OR=3.4, p< 0.001)
 History suicidal thoughts, (OR=2.5, p=0.002)
 Poorer reported health (OR= 2.1, p=0.01)
*Logistic regression controlling for other mental disorders &
health risk factors

23. Depression Associated with*
 Higher hospitalizations (OR=2.2, p=0.002)
 History suicidal thoughts (OR=8.3, p<0.001)
 History substance abuse treatment (OR=1.8,
p=0.01)
*Logistic regression controlling for other mental disorders &
health risk factors

24. Rx Opioid Dependence
Associated with*
 Higher pain impairment (OR=1.7, p = 0.007)
 History addiction treatment OR=2.3, p< 0.001)
 Poorer reported health (OR=1.8, p = 0.005)
*Logistic regression controlling for other mental disorders
& health risk factors

25. Study limitations
• Patients selected based on Rx in EHR
• Cross-sectional study design
• DSM-IV criteria in transition
• Sample size limited (N= 705)
• Population 96% White
• Mostly rural & non-urban region

26. Conclusion
 Chronic pain patients receiving opioids have history
of mental health disorders, including POD, GAD & MD
 These comorbidities are associated with pain
impairment, service utilization, suicidal thoughts, and
poor health status, potentially complicating patient care.
 PTSD was not associated with comorbidity, once
other variables were controlled.
 Study suggests that chronic pain patients on opioid
therapy may benefit by integration of mental health
services into primary and specialty care.

27. References
Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug
dependence among outpatients on opioid therapy in a large US
healthcare system. Addiction. 2010; 105(10):1776-1782.
Erlich PM, Hoffman SN, Rukstalis M, Han JJ, Chu X, Kao
WHL, Gerhard GS, Stewart WF, Boscarino JA. Nicotinic
acetylcholine receptor genes on chromosome 15q25.1 are
associated with nicotine and opioid dependence severity. Hum
Genet. 2010; 128: 491-499.
Boscarino JA, Rukstalis, MR, Hoffman SN, Han JJ, Erlich PM, Ross
S, Gerhard GS, Stewart WF. Prevalence of prescription opioid-use
disorder among chronic pain patients: Comparison of the DSM-5 vs.
DSM-4 diagnostic criteria. J Addict Dis. 2011; 30: 185-194.
Boscarino JA, Erlich PM, Hoffman SN, Rukstalis M, Stewart WF.
Association of FKBP5, COMT and CHRNA5 polymorphisms with
PTSD among outpatients at risk for PTSD. Psychiatry Res. 2011;
188: 173-174.