Abstract
Objective:
Psychiatric comorbidities complicate treatment of patients with chronic pain and opioid use disorder, but the prevalence of specific comorbid psychiatric disorders in this population has not been systematically investigated.
Methods:
170 consecutive participants entering a treatment research program for co-occurring chronic pain and opioid use disorder between March 2009 and July 2013 were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV).
Results:
The prevalence of any lifetime (and current) comorbid Axis I disorder was 91% (75%); 52% met criteria for lifetime anxiety disorder (48% current), 57% for lifetime mood disorder (48% current), and 78% for lifetime non-opioid substance use disorder (34% current). Common current anxiety diagnoses were posttraumatic stress disorder (21%), generalized anxiety disorder (16%), and panic disorder without agoraphobia (16%). Common current mood diagnoses were major depressive disorder (40%) and dysthymia (11%). A majority of patients had a personality disorder (52%).
Conclusion:
High rates and persistence of co-occurring psychiatric disorders, including anxiety or mood disorders, may explain in part the difficulty providers have treating patients with co-occurring opioid use disorder and chronic pain, and suggest possible targets for improving treatment.
Keywords: chronic pain, opioid-related disorders, mental disorders
INTRODUCTION
The use of opioid analgesics to treat chronic non-cancer pain (i.e., pain lasting at least three months) has increased three-fold since the early 1990s and has brought with it an epidemic of nonmedical opioid use, opioid overdose, and opioid use disorder1–5. Patients with co-occurring chronic pain and opioid use disorder present considerable management challenges: Unrelieved pain is associated with anxiety and depression, sleep problems, and opioid or other substance misuse, often to self-medicate6–9. Clinicians report difficulty managing patients with chronic pain and opioid use disorder because of the perceived high rates of accompanying psychopathology, a dearth of evidence-based treatments for these co-existing conditions, and a paucity of providers who specialize in their treatment10–12. Given their expertise in psychiatric assessment and treatment, prescribing adjuvant psychotropic pain medications (e.g., antidepressants), and the biopsychosocial model, psychiatrists can perform a pivotal role in the treatment of chronic pain and opioid use disorder13–15. However, many may feel ill-equipped to do so; medical schools and psychiatry residency programs in the U.S. provide limited training on managing chronic pain, especially in the context of an opioid use disorder13,16. Increased knowledge about the psychiatric comorbidity of co-occurring opioid use disorder and chronic pain might assist psychiatrists in treating or consulting on this vulnerable patient population.
High rates of psychiatric disorders have been found among patients with chronic pain17–22 and with opioid use disorder23–25 , and co-occurring psychopathology in patients with these disorders has important treatment implications26,27. Relatively few studies have investigated psychopathology among patients with co-occurring opioid use disorder and chronic pain, however. Elevated levels of anxiety and depression have been reported in surveys of methadone-maintained patients with chronic pain6,9,28,29, and one small study found high rates of Axis-I disorders among 40 patients with chronic pain referred from multidisciplinary pain clinics who also had either opioid abuse (n=12) or dependence (n=28)30. Although anxiety and depression can exacerbate pain in non-addicted patients with chronic pain26,31, the association of pain with anxiety disorders or with mood disorders has not been systematically examined in those with co-occurring opioid use disorder and chronic pain.
Consequently, this study evaluated the prevalence of DSM-IV-TR32 Axis I and Axis II disorders and the association between psychiatric disorders and pain intensity or pain interference (i.e., decrement in functioning resulting from pain) among patients with co-occurring opioid use disorder and chronic pain entering either of two clinical trials combining behavioral interventions and opioid agonist maintenance treatment with buprenorphine/naloxone or methadone. We anticipated that rates of Axis I psychiatric disorders would be even higher among patients with co-occurring opioid use disorder and chronic pain than those previously reported among patients with either condition alone. Finally, we hypothesized that in comparison to patients with neither an anxiety disorder nor a mood disorder, those with an anxiety disorder, a mood disorder, or both would have higher pain intensity and pain interference.
METHOD
Participants
Participants were a consecutive series of 170 adults who completed evaluations for enrollment in a treatment research program for co-occurring chronic pain and opioid dependence in New Haven, Connecticut, between March 2009 and July 2013. Participants were recruited through referrals from providers and intake workers at primary care centers, pain management clinics, and opioid treatment programs; advertisements (e.g., radio, Internet, posters in the community); and word-of-mouth. One hundred and thirteen participants were evaluated for a research protocol involving office-based buprenorphine/naloxone treatment (NCT006348030), while the remaining 57 were assessed for a research protocol involving opioid treatment program-based methadone maintenance treatment (NCT00727675). Participants were administered the diagnostic interviews following medication induction and initial stabilization (generally one to two weeks following initiation of either buprenorphine/naloxone or methadone). The study received appropriate Institutional Review Board and institutional approval (at Yale University School of Medicine and at APT Foundation). Participants provided voluntary, written informed consent. The study design and conduct complied with the Declaration of Helsinki.
To be eligible for study inclusion, participants needed to: 1) be at least 18 years old; 2) be able to read and write in English; 3) experience moderate to severe chronic low back pain (ratings of pain at its worst or peak in past week ≥4 on a 0 [no pain]-10 [worst pain imaginable] numeric rating scale) of at least six months duration and classified as non-specific in origin, according to the guidelines issued by the American College of Physicians (ACP) and the American Pain Society (APS)33; and 4) meet DSM-IV-TR criteria for opioid dependence32 and joint American Academy of Pain Medicine-American Pain Society-American Society of Addiction Medicine (AAPM-APS-ASAM) criteria for opioid addiction, which require compulsive use, continued use despite harm, or craving34. Participants could have multiple sites of pain, but low back pain was required to be a primary pain site. Exclusion criteria included drug treatment in the prior 30 days and current suicide or homicide risk. Participants received a comprehensive evaluation from a study physician prior to admission to ensure study eligibility.
Demographic and Clinical Characteristics
Participants provided information on demographics (age, gender, race, ethnicity, education, employment, marital status) and clinical characteristics (HIV status, primary drug of abuse [heroin, opioid medication, other], outpatient mental health visit in the past month [yes/no] and whether they had taken prescribed psychiatric medication in the past month [yes/no]).
Pain Characteristics
Participants provided information on current pain location and genesis, and the duration of chronic pain. Participants also completed the Brief Pain Inventory (BPI)35,36, where they rated four facets of pain experienced in the past seven days (i.e., “pain at its worst,” “pain at its least,” “pain on average,” “pain right now”) using 0 (“no pain at all”) to 10 (“pain as bad as you can imagine”) scales, and seven pain interference items that assessed the extent to which their pain in the last seven days had interfered with their “general activity,” “mood,” “walking ability,” “normal work (includes both outside the home and housework),” “relations with other people,” “sleep,” and “enjoyment of life” using 0 (“does not interfere”) to 10 (“completely interferes”) scales. The mean of the four pain intensity ratings was calculated to find the “pain severity score,” while the mean of the seven interference items was calculated to determine the “pain interference score” (both scored on 0 to 10 scales)37.
Diagnostic Interviews
The Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P)38 includes modules on current (last 30 days) and lifetime (either current or past) mood, anxiety, and substance use disorders, while the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV)39 collects diagnostic information pertaining to the last 2 years (i.e., current only) on Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), and Cluster C (avoidant, dependent, obsessive-compulsive) personality disorders.
Interviewers
The diagnostic interviews were conducted by addiction psychiatry and psychology fellows as well as clinical and counseling psychologists. A standardized training protocol was followed: research clinicians attended didactic workshops; observed two batteries performed by experienced assessors; conducted two supervised batteries; and subsequently conducted the diagnostic evaluations independently, receiving ongoing supervision as needed.
Data Analysis
Descriptive statistics were used to calculate demographic characteristics and the prevalence of psychiatric disorders. T-tests and chi-square tests were performed to compare baseline characteristics between patients from the buprenorphine/naloxone and methadone maintenance trials. Subsequent analyses examined the overall sample, using univariate analysis of variance (ANOVA) tests to compare pain severity scores and pain interference scores in patients with (a) co-occurring anxiety and mood disorders, (b) anxiety or mood disorder (but not both), and (c) no anxiety or mood disorders. Separate 2X2 chi-square tests were performed for participants in the buprenorphine/naloxone and methadone maintenance trials to determine whether the presence of any current or lifetime anxiety, mood, or non-opioid substance use disorder, or any current personality disorder was associated with study completion or clinically significant changes in pain severity or pain interference (defined as ≥ 2 decrease on 0–10 scales from baseline to end of treatment). Chi-square tests were also performed to examine differences between participants whose reported primary drug of abuse was heroin or prescription opioids on the presence of lifetime and current psychiatric disorders. The Fisher’s Exact test was used in cases where the expected cell frequencies for the chi-square tests was less than 5. Statistical significance was set at p<0.05. All statistics were performed on IBM® SPSS Statistics Version 19.
RESULTS
Demographic and Clinical Characteristics
The 170 participants ranged in age from 19 to 64 years old (M=36.0, SD=10.0); 71% were men; 87% were white; 47% were employed; 87% had greater than or equal to a high school education; 20% were married; and 51% reported opioid medications as their primary drug of abuse (Table 1). The average ages of onset of chronic pain and opioid dependence were 23.7 and 25.3, respectively. On average, participants in the buprenorphine/naloxone trial, in comparison to those in the methadone maintenance trial, were (p<0.05) younger (34.6 vs. 38.8 years old); more likely to be employed (56% vs. 28%) and report that opioid medication was their primary drug of abuse (61% vs. 30%); and less likely to report that they had been prescribed psychiatric medication in the past month (11% vs. 23%).
Table 1.
Demographic and clinical characteristics of patients with chronic pain and opioid dependence
| Buprenorphine (n=113) |
Methadone (n=57) |
Total (n=170) |
|
|---|---|---|---|
| Age, mean (SD)† | 34.6 (9.3) | 38.8 (10.6) | 36.0 (10.0) |
| Gender, % (n) | |||
| Male | 70.8 (80) | 71.9 (41) | 71.2 (121) |
| Female | 29.2 (33) | 28.1 (16) | 28.8 (49) |
| Race, % (n) | |||
| White | 86.7 (98) | 87.7 (50) | 87.1 (148) |
| African-American | 4.4 (5) | 5.3 (3) | 4.1 (7) |
| Other | 8.9 (10) | 7.0 (4) | 8.2 (14) |
| Ethnicity, % (n) | |||
| Hispanic | 9.7 (11) | 10.6 (6) | 10.0 (17) |
| Non-Hispanic | 90.3 (102) | 89.4 (51) | 90.0 (153) |
| Education, % (n) | |||
| Less than high school | 12.4 (14) | 14.0 (8) | 12.9 (22) |
| High school graduates | 86.7 (98) | 86.0 (49) | 86.5 (147) |
| Employment status, % (n)* | |||
| Employed (full time, part time, student) | 55.8 (63) | 28.1 (16) | 46.5 (79) |
| Unemployed (not employed, retired) | 44.2 (50) | 71.9 (41) | 53.5 (91) |
| Marital status, % (n) | |||
| Married | 21.2 (24) | 17.5 (10) | 20.0 (34) |
| Single/divorce/separated | 78.8 (89) | 82.5 (47) | 80.0 (136) |
| HIV status, % (n) | |||
| Positive | 1.8 (2) | 0.0 (0) | 1.2 (2) |
| Negative | 96.5 (109) | 96.5 (55) | 96.5 (164) |
| Never tested/uncertain | 1.8 (2) | 3.5 (2) | 2.4 (4) |
| Primary drug of abuse, % (n)* | |||
| Heroin | 38.1 (43) | 59.6 (34) | 45.3 (77) |
| Opioid medication | 61.1 (69) | 29.8 (17) | 50.6 (86) |
| Other | 0.9 (1) | 10.5 (6) | 4.1 (7) |
| Outpatient mental health visit in past month, % (n) | 3.5 (4) | 3.6 (2) | 3.5 (6) |
| Prescribed psychiatric medication in past month, % (n)* | 10.6 (12) | 23.2 (13) | 14.8 (25) |
t-test, p < 0.05
chi-square, p < 0.05
Pain Characteristics
The duration of pain ranged from <1 to 58 years (M=13.2, SD=10.6). Causes of current pain included accident (63%), nerve pain (22%), arthritis (18%), surgery (17%), opioid withdrawal (16%), work (14%), HIV (0.6%), and “other” (12%). Inclusive of low back, the number of reported pain sites ranged from 1 to 10 (M=3.0, SD=1.8), and comprised legs (48%), shoulder (29%), feet (21%), neck (20%), hands (17%), head (15%), stomach (14%), knees (14%), arms (13%), hips (9%), pelvis (9%), teeth (2%), face (1%), and “other” (6%). Participants’ average pain severity and pain interference scores were 5.6 (SD=1.5) and 6.0 (SD=2.3), respectively.
Psychiatric Disorder Prevalence, Persistence, Comorbidity, and Treatment
The prevalence of any lifetime (and current) comorbid Axis I disorder was 91% (75%). As summarized in Table 2, 52% met criteria for lifetime anxiety disorder (48% current), 57% for lifetime mood disorder (48% current), and 78% for lifetime non-opioid substance use disorder (34% current). A majority of patients had an Axis II disorder (52%). As summarized in Table 3, patients whose primary reported drug of abuse was heroin (compared to prescription opioids) were more likely to meet lifetime criteria for any Axis I disorder and any non-opioid substance use disorder as well as any current Axis II disorder.
Table 2.
Psychiatric diagnoses of patients with chronic pain and opioid dependence
| (n=170) | ||
|---|---|---|
| DSM-IV Psychiatric Diagnosis | Lifetime % (n) |
Current % (n) |
| Axis I Diagnosis: | ||
| Any Axis I disorder† | 90.6 (154) | 75.3 (128) |
| Anxiety disorders | ||
| Any anxiety disorder | 51.8 (88) | 48.2 (82) |
| Posttraumatic stress disorder | 23.5 (40) | 20.6 (35) |
| Generalized anxiety disorder | 15.9 (27) | 15.9 (27) |
| Panic disorder (without agoraphobia) | 15.9 (27) | 15.9 (27) |
| Social Phobia | 11.2 (19) | 9.4 (16) |
| Specific phobias | 5.9 (10) | 5.3 (9) |
| Obsessive-compulsive disorder | 7.1 (12) | 6.5 (11) |
| Panic disorder (with agoraphobia) | 3.5 (6) | 2.9 (5) |
| Substance induced anxiety disorder | 2.4 (4) | 2.4 (4) |
| Agoraphobia (no history of panic disorder) | 1.2 (2) | 1.2 (2) |
| Anxiety Disorder, NOS | 1.2 (2) | 1.2 (2) |
| Mood disorders | ||
| Any mood disorder | 57.1 (97) | 48.2 (82) |
| Major depressive disorder, recurrent | 25.3 (43) | 19.4 (33) |
| Major depressive disorder, single | 23.5 (40) | 20.6 (35) |
| Dysthymia | 10.6 (18) | 10.6 (18) |
| Bipolar disorder | 4.7 (8) | 4.7 (8) |
| Substance induced mood disorder | 2.4 (4) | 1.8 (3) |
| Depressive disorder, NOS | 0.0 (0) | 0.0 (0) |
| Cyclothymia | 0.0 (0) | 0.0 (0) |
| Adjustment disorder | 0.0 (0) | 0.0 (0) |
| Opioid dependence | 100.0 (170) | 100.0 (170) |
| Non-opioid substance use disorder | ||
| Any non-opioid substance use disorder | 77.6 (132) | 33.5 (57) |
| Alcohol dependence | 37.6 (64) | 4.7 (8) |
| Alcohol abuse | 19.4 (33) | 3.5 (6) |
| Cocaine dependence | 31.8 (54) | 14.1 (24) |
| Cocaine abuse | 11.4 (20) | 3.5 (6) |
| Cannabis dependence | 22.9 (39) | 10.0 (17) |
| Cannabis abuse | 18.8 (32) | 7.6 (13) |
| Sedative/hypnotic dependence | 6.5 (11) | 1.8 (3) |
| Sedative/hypnotic abuse | 8.8 (15) | 4.7 (8) |
| Other drug dependence | 7.1 (12) | 1.2 (2) |
| Other drug abuse | 5.7 (10) | 2.4 (4) |
| Axis II Diagnosis: | ||
| Any axis II disorder | N/A | 51.8 (88) |
| Paranoid personality disorder | N/A | 16.5 (28) |
| Schizoid personality disorder | N/A | 8.2 (14) |
| Schizotypal personality disorder | N/A | 0.0 (0) |
| Antisocial personality disorder | N/A | 21.8 (37) |
| Borderline personality disorder | N/A | 12.4 (21) |
| Histrionic personality disorder | N/A | 0.0 (0) |
| Narcissistic personality disorder | N/A | 0.0 (0) |
| Avoidant personality disorder | N/A | 18.8 (32) |
| Dependent personality disorder | N/A | 7.6 (13) |
| Obsessive-compulsive personality disorder | N/A | 11.2 (19) |
| Depressive personality disorder | N/A | 11.8 (20) |
| Axis IV: | ||
| Financial problems | N/A | 59.4 (101) |
| Problems with primary support group | N/A | 51.2 (87) |
| Occupational problems | N/A | 32.4 (55) |
| Lack of social support | N/A | 8.2 (14) |
| Relationship problems | N/A | 11.2 (19) |
| Unemployment | N/A | 13.5 (23) |
| Problems with access to medical care | N/A | 2.9 (5) |
| Homelessness | N/A | 1.8 (3) |
| Financial stress | N/A | 4.1 (7) |
| Problems with transportation | N/A | 1.2 (2) |
| Work-related problems | N/A | 1.8 (3) |
| Limited social network | N/A | 1.8 (3) |
| Family stress | N/A | 0.6 (1) |
| Housing problems | N/A | 1.8 (3) |
| Axis V: | ||
| GAF score, mean (SD) | N/A | 59.4 (4.8) |
Does not include diagnosis of opioid dependence
Table 3.
Comparison of psychiatric diagnoses in patients with chronic pain and opioid dependence by self-reported primary drug of abuse†
| DSM-IV Psychiatric Diagnosis | Heroin | PO | Heroin | PO | ||||
|---|---|---|---|---|---|---|---|---|
| Lifetime | X2 (df=1) |
p | Current | X2 (df=1) |
p | |||
| % | % | % | % | |||||
| Axis I Diagnosis: | ||||||||
| Any Axis I disorder | 97.4 | 84.9 | 7.620 | 0.005 | 80.5 | 68.6 | 3.015 | 0.059 |
| Anxiety disorders | ||||||||
| Any anxiety disorder | 53.2 | 50.0 | 0.171 | 0.399 | 53.2 | 43.0 | 1.702 | 0.126 |
| Posttraumatic stress disorder | 27.3 | 22.1 | 0.589 | 0.279 | 27.3 | 16.3 | 2.912 | 0.065 |
| Generalized anxiety disorder | 16.9 | 12.8 | 0.542 | 0.303 | 16.9 | 12.8 | 0.542 | 0.303 |
| Panic disorder (without agoraphobia) | 14.3 | 17.4 | 0.302 | 0.370 | 14.3 | 17.4 | 0.302 | 0.370 |
| Social Phobia | 14.3 | 9.3 | 0.980 | 0.228 | 11.7 | 8.1 | 0.578 | 0.309 |
| Specific phobias | 5.2 | 5.8 | 0.030* | 1.000 | 5.2 | 4.7 | 0.026* | 1.000 |
| Obsessive-compulsive disorder | 9.1 | 5.8 | 0.640 | 0.308 | 7.8 | 5.8 | 0.253 | 0.423 |
| Panic disorder (with agoraphobia) | 3.9 | 3.5 | 0.019* | 1.000 | 3.9 | 2.3 | 0.337* | 0.668 |
| Substance induced anxiety disorder | 2.6 | 1.2 | 0.463* | 0.603 | 2.6 | 1.2 | 0.463* | 0.603 |
| Agoraphobia (no history of panic disorder) | 1.3 | 1.2 | 0.006* | 1.000 | 1.3 | 1.2 | 0.006* | 1.000 |
| Anxiety Disorder, NOS | 2.6 | 0.0 | 2.262* | 0.222 | 2.6 | 0.0 | 2.262* | 0.222 |
| Mood disorders | ||||||||
| Any mood disorder | 59.7 | 53.5 | 0.646 | 0.259 | 48.1 | 46.5 | 0.039 | 0.484 |
| Major depressive disorder, recurrent | 35.1 | 16.3 | 7.615 | 0.005 | 26.0 | 12.8 | 4.584 | 0.026 |
| Major depressive disorder, single | 16.9 | 30.2 | 3.978 | 0.034 | 14.3 | 26.7 | 3.820 | 0.038 |
| Dysthymia | 6.5 | 12.8 | 1.820 | 0.139 | 6.5 | 12.8 | 1.820 | 0.139 |
| Bipolar disorder | 3.9 | 4.7 | 0.056* | 1.000 | 3.9 | 4.7 | 0.056* | 1.000 |
| Substance induced mood disorder | 2.6 | 2.3 | 0.013* | 1.000 | 2.6 | 1.2 | 0.463* | 0.603 |
| Depressive disorder, NOS | 0.0 | 0.0 | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Cyclothymia | 0.0 | 0.0 | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Adjustment disorder | 0.0 | 0.0 | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Opioid dependence | 100.0 | 100.0 | N/A | N/A | 100.0 | 100.0 | N/A | N/A |
| Non-opioid substance use disorder | ||||||||
| Any non-opioid substance use disorder | 88.3 | 69.8 | 8.285 | 0.003 | 39.0 | 27.9 | 2.241 | 0.092 |
| Alcohol dependence | 45.5 | 31.4 | 3.407 | 0.046 | 6.5 | 2.3 | 1.717* | 0.257 |
| Alcohol abuse | 16.9 | 22.1 | 0.699 | 0.262 | 2.6 | 4.7 | 0.483* | 0.685 |
| Cocaine dependence | 41.6 | 23.3 | 6.264 | 0.010 | 18.2 | 11.6 | 1.390 | 0.169 |
| Cocaine abuse | 15.6 | 8.1 | 2.187 | 0.109 | 5.2 | 2.3 | 0.943* | 0.423 |
| Cannabis dependence | 27.3 | 17.4 | 2.282 | 0.093 | 10.4 | 8.1 | 0.246 | 0.410 |
| Cannabis abuse | 23.4 | 16.3 | 1.297 | 0.173 | 9.1 | 7.0 | 0.247 | 0.416 |
| Sedative/hypnotic dependence | 10.4 | 2.3 | 4.588* | 0.048 | 2.6 | 0.0 | 2.262* | 0.222 |
| Sedative/hypnotic abuse | 9.1 | 9.3 | 0.002 | 0.590 | 5.2 | 4.7 | 0.026* | 1.000 |
| Other drug dependence | 7.8 | 5.8 | 0.253 | 0.423 | 1.3 | 1.2 | 0.006* | 1.000 |
| Other drug abuse | 9.1 | 3.5 | 2.214* | 0.193 | 2.6 | 2.3 | 0.013* | 1.000 |
| Axis II Diagnosis: | ||||||||
| Any axis II disorder | N/A | N/A | N/A | N/A | 61.0 | 44.2 | 4.624 | 0.023 |
| Paranoid personality disorder | N/A | N/A | N/A | N/A | 20.8 | 12.8 | 1.876 | 0.123 |
| Schizoid personality disorder | N/A | N/A | N/A | N/A | 10.4 | 5.8 | 1.159 | 0.216 |
| Schizotypal personality disorder | N/A | N/A | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Antisocial personality disorder | N/A | N/A | N/A | N/A | 26.0 | 18.6 | 1.282 | 0.173 |
| Borderline personality disorder | N/A | N/A | N/A | N/A | 11.7 | 12.8 | 0.046 | 0.511 |
| Histrionic personality disorder | N/A | N/A | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Narcissistic personality disorder | N/A | N/A | N/A | N/A | 0.0 | 0.0 | N/A | N/A |
| Avoidant personality disorder | N/A | N/A | N/A | N/A | 18.2 | 18.6 | 0.005 | 0.554 |
| Dependent personality disorder | N/A | N/A | N/A | N/A | 5.2 | 9.3 | 1.005 | 0.243 |
| Obsessive-compulsive personality disorder | N/A | N/A | N/A | N/A | 14.3 | 8.1 | 1.562 | 0.159 |
| Depressive personality disorder | N/A | N/A | N/A | N/A | 9.1 | 14.0 | 0.933 | 0.236 |
Primary drug of abuse was either heroin or PO (prescription opioids)
Fisher’s Exact Test used due to insufficient cell size
Bolded p-values were significant at p<.05.
The proportion of participants who met lifetime criteria for zero, one, two, or at least three comorbid psychiatric disorders (i.e., any anxiety disorder, any mood disorder, any non-opioid substance use disorder, any Axis II disorder) was as follows: 9%, 20%, 20%, and 51%, respectively, while the proportion who met current criteria were: 19%, 22%, 25% and 34%, respectively. About two-thirds of participants met criteria for current co-occurring anxiety or mood disorders (65%), including 33% who met criteria for both disorders. Participants’ average ages of onset for anxiety disorders and mood disorders were 16.9 (SD=10.8) and 23.3 (SD=10.3) years, respectively; the average durations of current anxiety disorders and current mood disorders were 12.3 (SD=10.7) and 18.2 (SD=12.5) years, respectively. Of participants meeting criteria for a lifetime anxiety disorder, 93% also met criteria for a current anxiety disorder; 84% of patients meeting criteria for a lifetime mood disorder also met criteria for a current mood disorder. In the month prior to baseline, 4% of participants reported attending a mental health appointment, 15% reported that they had taken a prescribed psychiatric medication, and 16% reported either having a mental health visit and/or taking a prescribed psychiatric medication.
Anxiety and Mood Disorders, Pain Severity, Pain Interference
Among participants with current co-occurring anxiety and mood disorders, either a current anxiety or mood disorder (but not both), or no current anxiety or mood disorders, there were no significant differences found in pain severity score (5.7 vs. 5.7 vs. 5.5, respectively) (F=0.53, df=2, 167, p=0.58) or pain interference score (6.3 vs. 6.0 vs. 5.7, respectively) (F=1.14, df=2, 167, p=0.32). Treatment retention and clinically significant changes in pain severity or pain interference were not significantly associated with the presence of current or lifetime psychiatric disorders (p values ranged from 0.12 to 1.00 and 0.06 to 1.00, respectively for participants in the buprenorphine/naloxone and methadone maintenance trials).
DISCUSSION
This study found a very high prevalence of DSM-IV-TR Axis-I and Axis-II disorders among patients seeking treatment for co-occurring opioid use disorder and chronic pain. Most participants (81%) met current criteria for at least one—and the majority (59%) for at least two—of the following psychiatric comorbidities: anxiety disorder, mood disorder, non-opioid substance use disorder, or personality disorder. Notably, a high proportion of participants with lifetime psychiatric disorders also met current diagnostic criteria. Despite the high prevalence and persistence of psychopathology, few participants had received either mental health treatment (3.5%) or a psychiatric medication in the past month (14.8%). Contrary to findings among patients with chronic pain but without co-occurring opioid use disorder26,31, in this study, the presence of an anxiety disorder, mood disorder, or both, was not associated with higher pain severity or pain interference scores.
To put the findings of the current study in context, the prevalence of current anxiety disorders (48%) among study participants was higher than found in prior studiesa of patients with opioid dependence (5–17%)23,24 or in studies of patients with chronic pain (11–25%)19–21. (Because of differences in study methodology, we did not make direct statistical comparisons between the current and prior studies.) Similarly, the prevalence of current mood disorders (48%) among study patients was higher than that found in studies of patients with opioid dependence (4–24%)23–25 and at the higher end of the range of those reported in studies of patients with chronic pain (34–56%)18,40. The prevalence of current non-opioid substance use disorders (34%) was in the range found in previous studies of patients with opioid use disorders (40–68%)24,25,41, but substantially higher than the estimated rates of substance use disorders reported in studies of patients with chronic pain (11–19%)20–22,42. The prevalence of personality disorders (52%) was also in the range reported in prior studies of patients with opioid use disorders (35–57%)23–25,43 or chronic pain (41–69%)18,20–22,44,45. Our findings are consistent with a previous investigation of a group of 40 patients with co-occurring opioid use disorders and chronic pain, which reported numerically even higher rates of lifetime anxiety (93%) and mood disorders (85%) than those found in this study30.
This study is among the first to document higher rates of any lifetime Axis I disorder, any lifetime non-opioid substance use disorder, and any current Axis II disorder among patients with co-occurring chronic pain and opioid dependence reporting heroin (compared to prescription opioids) as their primary drug of abuse, and this finding merits further investigation. While patients with an anxiety and/or mood disorder had numerically higher pain intensity and interference than their counterparts without these disorders, group differences did not reach the level of statistical significance, but may have done so with a larger sample size. However, it is also possible that the presence of an opioid (or non-opioid substance) use disorder attenuates the relationship previously reported between pain intensity or interference and the presence of anxiety or mood disorders among individuals with chronic pain26,31. One striking finding in this study was the high rate of non-opioid substance-related disorders; the extent to which the order of onset of chronic pain and opioid use disorder is associated with the prevalence of psychopathology, including non-opioid substance use disorders is currently unclear and should be further investigated.
Another important finding of the current study is the high persistence of lifetime anxiety or mood disorders into the present: 93% of patients meeting criteria for a lifetime anxiety disorder also met criteria for a current anxiety disorder, and 84% of patients meeting criteria for a lifetime mood disorder met criteria for a current mood disorder. The high prevalence of current psychiatric comorbidity at treatment entry as well as the persistence of these disorders, as indicated by the prolonged average duration of anxiety disorders (more than 12 years) and mood disorders (more than 18 years), may explain in part the clinical management problems experienced by providers treating these patients10,11. The findings suggest targets for potential pharmacological or psychosocial treatments (e.g., duloxetine and other antidepressant medications46 and cognitive-behavioral therapy47-49 have demonstrated efficacy in treating anxiety disorders, mood disorders, and chronic pain). It is notable, however, that neither lifetime nor current psychiatric disorders in the buprenorphine/naloxone or methadone maintenance trials were associated with study completion or clinically significant changes in pain severity or pain interference. This supports the conceptualization of these patients as persons with multiple interrelated morbidities who may benefit from the development and evaluation of integrated patient-centered interventions targeting chronic pain, opioid dependence, and other psychopathology.
Considering the high level of psychiatric comorbidity, it is noteworthy that a minority of participants (16%) reported past-month receipt of a psychiatric medication or a mental health treatment episode. This low treatment rate may be related to multiple factors, including: a) failure of healthcare professionals to identify and treat psychiatric disorders in this patient group; b) appropriate concerns about the use of benzodiazepines to treat anxiety disorders in this population; c) lack of access to psychiatrists or psychologists with expertise in treating co-occurring opioid use disorder and chronic pain in addition to other psychiatric disorders; d) logistical barriers (e.g., financial cost); and e) patient-level factors (e.g., lack of awareness of having a potentially treatable psychiatric disorder rather than simply experiencing symptoms of anxiety or depression related to chronic pain or opioid use disorder).
Several potential study limitations are worth noting. We did not collect data on the reliability of the study diagnoses (e.g., test-retest, inter-rater), but use of doctoral-level experienced clinicians as interviewers mitigates this concern. We used DSM-IV-TR32 (and not DSM-550) diagnoses. Given the importance of the construct of craving in both DSM-5 criteria for opioid use disorder50 and joint AAPM-APS-ASAM criteria for opioid addiction34, future research might benefit from a more detailed assessment of opioid craving51,52. The extent to which anxiety disorders and mood disorders among participants were primary, or a function of chronic pain or substance use, is unclear. Since participants were seeking treatment for co-occurring chronic pain and opioid dependence, it is unclear whether findings generalize to non-treatment-seeking individuals with these co-existing conditions.
Among patients seeking treatment for opioid use disorder and co-occurring chronic pain, the high rates of current and lifetime Axis I and Axis II disorders, the apparent absence of remission of anxiety disorders and mood disorders and the low rates of current mental health treatment are salient. Overall, our findings suggest that effective treatments for co-occurring chronic pain and opioid dependence may need to address co-occurring psychiatric disorders, especially given their apparent chronicity, and that strategies for improving access to psychiatric and mental health services for these patients are needed.
Clinical Points:
This study found high rates of current and lifetime Axis I and Axis II psychiatric disorders in patients with co-occurring chronic pain and opioid dependence.
This study also found that despite the long duration of current Axis I psychiatric disorders and the persistence of these disorders, very few participants had received mental health treatment or a psychiatric medication in the past month.
The high rates and persistence of psychiatric disorders and low rates of current mental health treatment among participants with co-occurring chronic pain and opioid use disorder suggest important clinical targets in developing treatments for of these co-occurring chronic medical conditions.
Acknowledgments
Conflicts of Interest and Source of Funding: This research was supported by funding from the National Institute on Drug Abuse to Dr. Barry (K23 DA024050) and Dr. Schottenfeld (K24 DA000445, R01DA024695). Dr. Kerns was supported by the Veterans Health Administration Health Services Research and Development Service Center of Innovation (CIN 13–407). None of the authors are affiliated with the tobacco, alcohol, pharmaceutical or gambling industry in a manner that we believe represents a conflict of interest with the current manuscript. The findings of this study were presented in part at the 75th Annual Scientific Meeting of the College on Problems of Drug Dependence—San Diego, CA, June 2013.
Footnotes
Role of the sponsors: The sponsors had no role in the design or conduct of the study. The views expressed in this article are those of the authors and do not necessarily represent the position or policy of the Department of Veterans Affairs or NIDA.
In these comparisons, we looked at studies using either DSM-III-R, DSM-IV, or DSM-IV-TR diagnostic criteria for the SCID (Axis I/Axis II) and DIPD (Axis II) to determine diagnostic prevalence.
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