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. Author manuscript; available in PMC: 2010 Oct 1.
Published in final edited form as: J Affect Disord. 2009 Feb 8;117(3):151–156. doi: 10.1016/j.jad.2009.01.011

Factors associated with Pain Interference in an Epidemiologic Sample of Adults with Bipolar I Disorder

Benjamin I Goldstein 1, Patricia R Houck 1, Jordan F Karp 1
PMCID: PMC2774129  NIHMSID: NIHMS147722  PMID: 19203799

Abstract

Objective

Epidemiologic studies have found that major depressive disorder (MDD) and anxiety disorders are associated with pain. However, little is known regarding the prevalence and correlates of pain in bipolar I disorder (BD).

Method

The 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample (N = 43,093) of the U.S. adult population, was used to determine if 1) prevalence of moderate-or-greater pain interference is elevated among subjects with 12-month history of BD, and 2) psychiatric and medical comorbidities independently contribute to increased pain interference in BD.

Results

Subjects with BD were significantly more likely to report pain interference of at least moderate severity compared to subjects without BD (24.8% versus 11.9%, p<0.001). Moderate or greater pain interference is also significantly more common among subjects with BD than those with MDD (20.3%) or anxiety disorders (19.3%; p<0.001). Logistic regression analyses adjusting for potential confounding variables indicated that BD is independently associated with increased pain interference (adjusted odds ratio 1.57, 95% confidence interval 1.39–1.78). Factors associated with pain interference in BD included greater age, non-white race, lower income, increased frequency of arthritis and other medical problems, comorbid anxiety disorders, and comorbid substance use disorders.

Conclusions

The prevalence of pain interference is elevated in BD, even compared to MDD or anxiety disorders, and is associated with both medical and psychiatric comorbidities. Interference from pain may be an important variable to consider in the assessment and treatment of BD. Future prospective studies are needed to determine the direction of the observed associations.

Keywords: pain, bipolar disorder, comorbidity, epidemiologic

INTRODUCTION

The bidirectional relationship between persistent pain and depressive disorders is broadly acknowledged (Arnold et al., 2004; Hudson et al., 2004; Meyer et al., 2007). It is known that persistent pain is both a risk factor for and a consequence of major depressive disorder (MDD)(Bair et al., 2003). In addition to predicting the onset of a persistent pain condition(Carroll et al., 2004), the presence of a depressive disorder has been shown to worsen both the pain experience(Lin et al., 2003),(Katon and Sullivan, 1990) and associated disability(Hudson et al., 1992; Hudson et al., 1985). There is evidence that co-occuring MDD and anxiety disorders are associated with additive burden of pain.(Bair et al.) Moreover, recent findings that chronic pain conditions are associated with increased risk of suicidality among persons with mental disorders are concerning.(Ratcliffe et al., 2008)

Epidemiologic studies can minimize the selection bias (e.g., Berkson bias(Walter, 1980)) inherent in studies of treatment-seeking samples with co-occurring conditions such as pain and psychiatric disorders. Studies of comorbid pain and psychiatric conditions have quantified pain in different ways, including pain intensity, pain interference, type of pain, number of pain problems, and pain-related role impairment. For example, in their evaluation of mood disorders associated with chronic pain using data from the National Comorbidity Survey (NCS)(Kessler et al., 1994), McWilliams et al assessed 1) pain intensity and 2) a generic probe of how much health problems cause disability (McWilliams et al., 2003). Other work from this group reported rates of psychiatric conditions as a function of type of painful condition (McWilliams et al., 2004). Results from the World Mental Health Survey reported rates of comorbid psychiatric conditions and number of pain problems (Gureje et al., 2008). Others have also examined the association between chronic pain and mental disorders in the NCS and demonstrated the importance of controlling for comorbid medical and psychiatric disorders when examining the independent burden of spinal pain in terms of role disability.(Von Korff et al., 2005) Another study found that a strong association exists between mood and anxiety disorders and chronic back and neck pain, and that this association is observed across the world.(Demyttenaere et al., 2007)

We set out to extend the knowledge base in this area by examining the prevalence and correlates of pain interference in a representative sample of adults with BD in the National Epidemiologic Survey on Alcohol and Related Conditions. Measurement of pain has been historically divided into intensity and interference. Whereas pain intensity represents the degree of pain unpleasantness, pain interference taps the disability resulting from pain. It is a measure of perceived disruption in daily activities, life roles, employment, and interpersonal relationships as a consequence of pain.

Previous pain-related findings in BD are scant. There is epidemiologic evidence of increased prevalence of migraine in BD(McIntyre et al., 2006), and some have hypothesized that migraine in unipolar depressed patients may represent a bipolar spectrum trait(Oedegaard and Fasmer, 2005). There is also clinical evidence that a variety of painful conditions are common in BD(Carney and Jones, 2006; Hansell, 1990; Kilbourne et al., 2004; Low et al., 2003). However, to date it is not known whether BD is also associated with overall pain interference. We hypothesized that subjects with 12-month history of BD would be significantly more likely than those without BD to report recent pain interference of at least moderate severity, and that this association would persist after controlling for factors that might confound the association between BD and pain interference, including age(Lariviere et al., 2007), gender (Greenspan et al., 2007), income(Brekke et al., 2002), race(Cano et al., 2006), education (Deyo et al., 2006; Harris et al., 2007), opioid and other substance abuse (Martell et al., 2007), and medical comordity (e.g., arthritis, obesity) (Hitt et al., 2007; Lawrence et al., 1998). Second, we hypothesized that among persons with BD comorbid anxiety disorders and substance use disorders (SUD), in addition to medical conditions, would be associated with increased prevalence of pain interference as compared with BD alone. Finally, we examined in an exploratory fashion the other putative predictors of pain interference among subjects with BD, and the prevalence of pain interference in BD compared to MDD or anxiety disorders.

METHODS

Sample

Subjects were identified from among the respondents of the cross-sectional 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC(Grant et al., 2004)). The NESARC is a representative sample of the United States conducted by the National Institute on Alcoholism and Alcohol Abuse (NIAAA). A detailed description of the NESARC can be found elsewhere(Grant et al., 2004). Briefly, 43,093 non-institutionalized civilian respondents, 18 years and older, completed face-to-face computer-assisted personal interviews. The overall survey response rate was 81%(Grant et al., 2004). The NESARC oversampled African Americans, Hispanics, and adults aged 18–24 years. The NESARC sample was weighted to adjust for oversampling and for household- and person-level nonresponse. Weighted data were adjusted to be socio-demographically representative of the US population based on the 2000 Decennial Census. For this analysis, respondents were divided into two groups based on the presence (N=883) versus absence (N=42,210) of 12-month BD.

Assessment

Approximately 1800 lay interviewers with an average of 5 years’ related experience administered the NESARC using laptop computer-assisted software. Interviewers completed 10 days of centralized, standardized training sessions. Demographic data ascertained from the NESARC included age, sex, education, race, marital status, and household income.

Pain Interference

Pain interference was assessed with the question, “During the past 4 weeks, how much did pain interfere with your normal work including both work outside the home and housework?” Subjects selected one of 5 levels of pain interference: “not at all,” “a little bit,” “moderately,” “quite a bit,” or “extremely.” For the purpose of the present report, pain interference was dichotomized into either present moderately or greater versus less than moderately, based on the response to this question. This question was derived from the Short Form-12 version 2 questionnaire.(Ware et al., 2002)

Psychiatric Diagnoses

The NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV) was used to generate the diagnoses presented in this report. The AUDADIS-IV diagnoses of substance use disorders and of mood and anxiety disorders have previously demonstrated reliability and validity (Grant et al., 2003; Grant et al., 2004; Grant et al., 2005; Hasin et al., 2005). Subjects were considered to have BD if they had a manic or mixed episode in the past 12 months, or if they had a major depressive episode in the past 12 months along with a prior lifetime manic or mixed episode.

Medical Comorbidity

The diagnosis of arthritis was determined with the question, “In the past 12 months, did a doctor or other health professional tell you that you had arthritis?” Other medical diagnoses queried in similar fashion included: arteriosclerosis, hypertension, angina, tachycardia, myocardial infarction, other heart disease, cirrhosis, other liver disease, stomach ulcer, and gastritis. Twenty-eight percent of the sample had one or more non-arthritis medical conditions, and only 8.4% had two or more. Non-arthritis medical conditions were therefore dichotomized as present versus absent. Arthritis was considered separately in analyses. Body mass index (BMI) was computed from self-reported height and weight. Subjects with BMI >30 were considered obese.

Substance Use

The NESARC provides information regarding abuse and dependence of alcohol and illicit drugs. For the purpose of this report, a category of substance use disorder (SUD) was computed. Subjects with a 12-month prevalence of abuse or dependence of alcohol or any substance other than nicotine or caffeine were considered to have a SUD. Because of the known association between opioids and pain, subjects were additionally categorized based on the presence of any opioid use in the past 12 months.

Statistical analyses

Chi-square analysis and T-tests were used to compare differences between these groups on categorical and dimensional measures respectively. Statistical significance was corrected for multiple comparisons (0.05/14) and only variables with between-group differences significant at the p<0.003 level were included in regression analyses. Multiple logistic regression analyses were conducted to control for potential confounds and derive adjusted odds ratios for pain interference associated with BD. We repeated the same regression analyses separately for subjects with BD to examine for factors independently associated with pain interference among participants with BD.

In order to provide nationally representative estimates and account for the complex survey design, we used the SURVEY procedures in the SAS statistical package (SAS Institute, Inc., Cary, N.C.) for all analyses, with appropriate weighting. Standard errors and 95% confidence intervals were estimated using Taylor series linearization to adjust for the design effects of complex sample surveys such as the NESARC.

RESULTS

Hypothesis #1: Increased Pain Interference among Subjects with BD

Data regarding pain interference are summarized in Table 1, as are demographic, medical, and substance-related data. As predicted by our first hypothesis, the omnibus comparison found significant between-group differences in the prevalence of pain interference (F=132.22, p<0.001). In terms of demographic variables, between-group differences were significant for age, sex, education, marital status, and household income. We included these variables as covariates in subsequent logistic regression analyses in which pain interference was the dependent variable in order to examine whether BD is independently significantly associated with pain interference.

Table 1.

Pain interference and other characteristics among subjects with and without bipolar disorder

BD
(n=883)		 Non BD
(n=42210)		 For
Rao-Scott
chisquare		 df p
Pain interference (%) 24.8 11.9 132.22 1 .0001
Age (M±SD) 36.9±0.3 45.4±0.1 202.42 1,369 .0001
Female (%) 57.0 52.0 8.59 1 .018
White race (%) 84.4 83.2 0.82 1 .40
<Highschool education (%) 20.2 15.6 13.75 1 .003
Married (%) 45.2 62.0 101.04 1 .0001
Household income (M±SD)1 36.5±0.6 54.4±0.2 193.55 1,369 .0001
Arthritis (%)2 25.5 17.3 39.82 1 .0001
Obese (BMI>30) (%) 30.2 22.3 29.67 1 .0001
Medical condition3 37.5 25.7 59.41 1 .0001
Anxiety 39.6 5.0 1879.53 1 .0001
Opioid use (%)4 7.7 1.7 172.83 1 .0001
Substance use disorder (%)5 49.2 18.2 535.61 1 .0001
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1

thousands of US dollars per year;

2

physician-diagnosed arthritis;

3

physician-diagnosed conditions other than arthritis;

4

any past-year opioid use;

5

abuse or dependence of non-nicotine drugs.

Participants with BD were significantly younger and reported significantly lower mean household income than those without BD. BD participants reported significantly more physician-diagnosed arthritis, other medical conditions, obesity, anxiety disorders, SUD, and any opioid use within the past 12 months. We included these variables as covariates in subsequent logistic regression analyses.

Logistic regression analyses were performed to examine whether BD is an independent predictor of pain interference after controlling for potential confounding demographic or clinical variables within the entire NESARC sample. The following variables were included: BD, age, sex, race, education, marital status, household income, arthritis, other medical problems, obesity, anxiety disorders, SUD, and any opioid use. BD was independently significantly associated with moderate or greater pain interference (OR 1.57, 95% CI 1.39–1.78).

We also examined the prevalence of moderate or greater pain interference across 4 groups: subjects with 12-month BD, subjects with 12-month MDD (N=2579), subjects with 12-month anxiety disorders but not MDD or BD (N=1436; generalized anxiety disorder, panic disorder with or without agoraphobia, or generalized anxiety disorder), and subjects with none of these conditions (N=37855). The prevalence of moderate or greater pain interference was greatest in the BD group (24.8%), which was significantly higher than in the MDD (20.3%) and anxiety (19.3%) groups, which was in turn significantly greater than in the group with none of these disorders (11.0%; χ2=847.8, df=3, p<0.001).

Hypothesis #2: Comorbid Anxiety Disorders and SUD are associated with Increased Pain Interference among Subjects with BD

The same regression analyses were repeated separately for subjects with and without BD in order to test hypothesis #2. These same analyses simultaneously examined in exploratory fashion the putative predictors of pain interference in each of these samples. As hypothesized, comorbid anxiety disorders among subjects with BD were significantly associated with increased prevalence of moderate or greater pain interference (OR 1.72, 95% CI 1.41–2.10). In addition, being married (OR 1.33, 95% CI 1.08–1.64) and having comorbid SUD (OR 1.91, 95% CI 1.56–2.34) were also significantly associated with pain interference among BD subjects. Other variables independently associated with at least moderate pain interference included greater age (χ2 = 44.88, df = 1, p < 0.001), lower income (χ2 = 42.74; p<0.001), white race (OR 0.47, 95% CI 0.40–0.55), arthritis (OR 2.84, 95% CI 2.24–3.58), and other medical disorders (OR 2.21, 95% CI 1.83–2.67).

DISCUSSION

The results of this study indicate that, in a representative sample of the United States population, subjects with BD are significantly more likely than those without BD to suffer from pain interference of at least moderate severity. Moreover, moderate or greater pain interference is more common among subjects with BD than among those with MDD or anxiety disorders. Although the present study examined pain interference, these findings largely converge with and extend those of previous epidemiologic studies that showed greater pain intensity among persons with anxiety disorders and with MDD (McWilliams et al., 2003; McWilliams et al., 2004; Ohayon and Schatzberg, 2003). Comorbid anxiety disorders and SUD were independently associated with pain interference among subjects with BD. Other significant predictors of pain interference among BD participants included older age, non-white race, being married, lower income, arthritis, and other medical disorders. To our knowledge, this is the first study to demonstrate elevated pain interference in a representative population sample of adults with BD.

In contrast to the sizeable literature regarding the epidemiologic association between pain and MDD (McWilliams et al., 2003; McWilliams et al., 2004), there is a relative paucity of data regarding BD and pain. Nonetheless, our finding of increased pain interference among persons with BD converges with the few previous studies on this topic. In an early case series, pain was the most common physical complaint among adults hospitalized for mania, and was prevalent in 102/302 (34%) patients(Hansell, 1990). A recent study using health-maintenance organization data found a 1.5-to 2.5-fold increased risk of painful conditions (headache, backache, arthritis) among BD subjects, in comparison to controls, after adjustment for potential confounds such as age and gender(Carney and Jones, 2006). Another study of BD patients receiving care in Veteran’s Administration facilities reported a significantly increased prevalence of lower back pain among subjects with, versus without, BD(Kilbourne et al., 2004). Although these samples are population based, they are also treatment-seeking samples and therefore not truly epidemiologic. Increased prevalence of migraine in BD has been reported in both clinical(Low et al., 2003) and epidemiologic(McIntyre et al., 2006) studies. The present findings demonstrate that BD is associated with elevated pain interference in an epidemiologic, non-treatment seeking sample.

The association of both anxiety disorders and SUD with pain interference among subjects with BD suggests the possibility that treatment of pain may attenuate these comorbidities. Another interpretation of these findings is that treatment of psychiatric morbidity may have benefits in terms of preventing or reducing pain interference. These different possibilities will be informed by future longitudinal studies. Such studies may also clarify why being married is associated with significantly increased pain interference among BD subjects, but not among overall NESARC subjects, as this finding was unexpected.

Opioid use was significantly associated with pain interference in the overall NESARC sample but not among BD subjects. A recent report found that 27% of BD subjects who had been prescribed opioid analgesics experienced subsequent clinically significant manic symptoms(Schaffer et al., 2007). Therefore, one explanation for the lack of a significant association between opioid use and pain interference among subjects with BD may be that people with BD who take opioids therapeutically are treated with analgesics that are less likely to precipitate mania. Unfortunately, the NESARC data do not allow for a direct examination of this hypothesis. Nonetheless, given that this is the first epidemiologic study of pain interference in BD, replication of these findings is warranted.

These findings must be interpreted in the context of several methodologic limitations. First, pain interference was ascertained using a single SF-12 item. This precluded an examination of specific pain details including intensity of pain, location of pain (headache, musculoskeletal, abdominal) and the time-course of pain (≥1 month versus <1 month). Similarly, it could not be determined whether pain interference was manifested in work-related or domestically-related difficulties, or both. Second, this study employed a cross-sectional retrospective methodology. As such, the direction of the associations between the variables cannot be determined. Third, the NESARC study did not include information regarding overall pain-related treatment. Although we examined the association between pain interference and any opioid use, the use of acetaminophen, anti-inflammatories, and non-pharmacologic interventions could not be determined. Such data would have provided further validation of pain interference. Fourth, as with any large-scale epidemiologic study, this study is limited by its reliance on lay interviewer-administered structured interviews to determine psychiatric diagnoses. Fifth, this study does not address any putative pathophysiological mechanisms for the observed findings, as the NESARC does not include any biological variables.

Taken together, the findings of this study suggest that the there is increased pain interference among persons with BD, and that this increase is independent of multiple potential confounding factors. Although many previous studies have examined the burden of pain in MDD, the results of this study indicate that the burden of pain in BD is equally concerning. Strategies for early identification of pain are needed in order to minimize the putative consequences of pain among persons with mood disorders, which may include decreased antidepressant treatment response (Karp et al., 2005aa; Karp et al., 2005b), substance use, and suicidality (Juurlink et al., 2004; Ratcliffe et al., 2008; Tang and Crane, 2006). Given that BD is a major risk factors for suicide, further study of potential additive effects are warranted. Although previous studies have examined predictors of suicide in BD(Oquendo et al., 2006), to our knowledge pain has been largely overlooked. This is of particular importance for mental health practitioners, for whom routine assessment of pain may not yet be part of clinical practice.

Treatments that target pain amelioration among persons with mood and anxiety disorders are urgently needed. To date, dual-action medications that enhance serotonergic and noradrenergic neurotransmission simultaneously have been shown to improve both pain and symptoms of depression (Detke et al., 2002) or anxiety (Russell JM, 2007). However, use of these agents in BD is problematic because of the significant risk of inducing mania (Ghaemi et al., 2003) There is also evidence supporting the use of non-pharmacologic interventions targeting anxiety or depression as well as pain (Christie et al., 2007; Otto et al., 2007; Rooks et al., 2007). Nonetheless, further research is needed in order to identify treatment strategies in this high-needs population. For example, studies have yet to examine the impact on pain of anti-epileptic medications such as lamotrigine, valproate and topiramate among persons with BD.

We advocate that systematic assessment of pain should be undertaken as part of the management of BD, and that this parameter should be monitored during the course of treatment. Potential benefits of early identification and treatment of pain among persons with mood and anxiety disorders include reduced pain interference, reduced health-care costs, and improved mood and anxiety treatment outcomes. Future studies employing prospective longitudinal methodology are needed in order to better understand the nature of the associations (e.g., antecedent vs. consequence) between pain, mood and anxiety disorders, and related medical and psychiatric comorbidities. Similarly, biological studies are needed to gain insights regarding the pathophysiological underpinnings of the elevated burden of pain in BD.

Table 2.

Logistic models with adjusted odds ratios for pain interference

Overall NESARC BD subjects
Adjusted Odds Ratio (95% Confidence Interval)
Age 1.01 [1.01,1.01]*** 1.03 [1.02,1.03]***
Female 1.06 [1.01,1.10]** 1.04 [0.84,1.29]
White race 0.87 [0.83,0.91]*** 0.47 [0.40,0.55]**
Married 1.03 [0.99,1.08] 1.33 [1.08,1.64]**
Less than high school 1.39 [1.31,1.48]*** 1.24 [0.91,1.69]
Household income1 1.00 [1.00,1.00]*** 1.00 [1.00,1.00]***
Arthritis 2.88 [2.74,3.03]*** 2.84 [2.24,3.58]***
Obese (BMI>30) 1.22 [1.17,1.28]*** 1.10 [0.88,1.39]
Medical condition2 1.84 [1.75,1.94]*** 2.21 [1.83,2.67]***
Anxiety3 1.46 [1.33,1.60]*** 1.72 [1.41,2.10]***
Substance Use Disorder4 1.30 [1.21,1.39]*** 1.91 [1.56,2.34]***
Opiod use5 1.43 [1.26,1.63]*** 0.93 [0.74,1.18]
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*

p<.05;

**

p<.01;

***

p<0.001

1

thousands of US dollars per year;

2

physician-diagnosed conditions other than arthritis;

3

Anxiety (social phobia, panic disorder, or generalized anxiety disorder)

4

abuse or dependence of alcohol or non-nicotine drugs;

5

any past-year opioid use

Acknowledgment

The NESARC is supported by the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md, with supplemental support from the National Institute on Drug Abuse, Bethesda. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of the sponsoring organizations.

Supported in part by: R25MH060473, The John A. Hartford center of Excellence in Geriatric Psychiatry, and Grant Number KL2 RR024154 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.

Footnotes

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