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 ConferenceMay 1, 2012 (Session B7)

HMORN Presentation 4-24-12.ppt

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.

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.

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.

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.

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).

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.

DSM-IV Criteria

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.

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

2459 adult patients– 9 primary care & 3 specialty clinics– ≥4 prescriptions– not cancer-related– July 2006 – June 2007

2373 attempted contact (mail/phone)

1390 actually contacted (8/07–11/08)

705 consented & completed interview

505 genotyped

86 not contacted (study quota met)

983 not reachable or not qualified– Institutionalized (nursing home, correctional

facility, mental institution, etc.)– Incapable of answering questions– Language barrier– Denied taking medications– Deceased– Disconnected phone– Busy signal/answering machine– Business/wrong number

685 Not interested/declined study

Sample design

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.

Staff Certification and Training are Important

World Health OrganizationComposite International

Diagnostic Interview (CIDI)

Prevalence of Opioid Dependence*

Dependence Measures Total SamplePercent 95% C.I. (N)

Lifetime Drug Dependence

Percent 95% C.I. (N)

No Lifetime DependencePercent (N)

Lifetime Opioid Depend.

% Yes

% No

Current Opioid Depend.

% Yes

% No

35.1 30.6-39.8 (251)

64.9 60.3-69.4 (454)

25.4 21.7-29.5 (181)

74.6 70.5-78.3 (524)

100.0 --- (251)

--- --- ---

72.4 67.3-77.0 (181)

27.6 23.0-32.7 (70)

--- ---

100.0 (454)

0.0 (0)

100.0 (454)

*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.

Lifetime DSM-5 Opioid-use Disorder vs. Lifetime DSM-4 Opioid Dependence

(tolerance & withdrawal dropped, craving added, abuse added, except legal

probs)

*Kappa = 0.873, p < 0.0001 for DSM-4 vs. DSM-5.

Diagnostic Criteria Used*DSM-5 Opioid-use

Disorder not Present

% 95% CI (n)

DSM-5 Opioid-use

Disorder Present

% 95% CI (n)

Total DSM-4 Opioid

Dependence

% 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)

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.

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.

Why are DSM-4 and DSM-5 Results the Same?

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.

Study PredictorsTotal SamplePercent (N)

LifetimeDrug

DependencePercent (N)

No Lifetime Drug

DependencePercent (N)

Lifetime Opioid Drug Abuse

% Yes

% No

12.3 (88)

87.7 (617)31.8 (79)

68.3 (172)

1.9 (9)***

98.1 (445)

Severity Opioid Dependence

% High

% Not High

15.1 (108)

84.9 (597)30.4 (77)

69.6 (174)

6.8 (31)***

93.2 (423)

Lifetime Alcohol Dependence

% Yes

% No

9.7 (68)

90.3 (637)14.3 (36)

85.7 (215)

7.1 (32)**

92.9 (442)

Lifetime Tobacco Dependence

% Yes

% No

36.3 (251)

63.7 (454)41.8 (103)

58.2 (148)

33.4 (148)***

66.6 (306)

Lifetime Posttraumatic Stress

% Yes

% No

13.1 (97)

86.9 (608) 21.3 (55)

78.7 (196)

8.7 (42)***

91.3 (412)

Opioid Dependence by Select Predictors

*** p<0.001

** p<0.01

** p<0.01

*** p<0.001

Study Predictors Total SamplePercent (N)

LifetimeDrug Dependence

Percent (N)

No Lifetime Drug DependencePercent (N)

History Childhood Neglect

% High

% Not High

24.6 (178)

75.4 (527) 33.0 (84)

67.0 (167)

20.1 (94)**

79.9 (360)

History Exposure to Psych Trauma

% High

% Not High

22.5 (161)

77.5 (544) 31.8 (80)

68.2 (171)

17.5 (81)***

82.5 (373)

History Illicit Drug Use

% Yes

% No

38.1 (273)

61.9 (432) 50.3 (127)

49.7 (124)

31.5 (146)***

68.5 (308)

History Substance Abuse Treat.

% Yes

% No

21.8 (153)

78.2 (552) 36.4 (90)

63.6 (161)

13.9 (63)***

86.1 (391)

History Anti-Social Personality

% Yes

% No

23.3 (167)

76.7 (538) 32.7 (83)

67.3 (168)

18.3 (84)***

81.7 (370)

(N =) (705) (251) (454)

*** p<0.001

** p<0.01

Opioid Dependence by Select Predictors (cont’d)

** p<0.01

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)

Logistic Regression Results Predicting Drug Dependence*

Model 1:

Lifetime Opioid Dependence

Model 2:

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.

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.

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%

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

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

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

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

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.

ReferencesBoscarino 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.