Association between generalized anxiety levels and pain in a community sample: Evidence for diagnostic specificity
Introduction
Generalized anxiety disorder (GAD) is a common condition in the general population (lifetime prevalence 5–6%) associated with significant individual and societal burden as well as tremendous health care costs (Olfson & Gameroff, 2007; Ormel et al., 2008; Ruscio et al., 2007; Wittchen, Beesdo, & Kessler, 2002). The occurrence of GAD with other mental disorders, particularly depression, has been studied extensively (Judd et al., 1998; Kessler, Walters, & Wittchen, 2004; Moffitt et al., 2007; Wittchen, Kessler, et al., 2002), but the relationship between GAD and pain conditions has only recently received some research attention. Primary care patients with GAD frequently present to their general practitioner with pain as initial reason for help-seeking (Wittchen, Kessler, et al., 2002). In addition, GAD patients suffer greater overall pain interference, compared to unaffected patients, and also have disproportionally high medical health care costs (Olfson & Gameroff, 2007).
Recent epidemiologic data provide evidence for strong associations between GAD and pain conditions (Demyttenaere et al., 2007; Gureje et al., 2008; McWilliams, Cox, & Enns, 2003; McWilliams, Goodwin, & Cox, 2004; Von Korff, Crane, et al., 2005). For example, in the National Comorbidity Survey—Replication (NCS-R), GAD appeared among several anxiety disorders to be particularly strongly related to chronic back pain (Von Korff, Crane, et al., 2005). A similar finding was reported from the World Mental Health surveys across 18 developing and western countries (Demyttenaere et al., 2007) where GAD was found to have a higher pooled odds ratio than the other anxiety disorders, major depression and alcohol abuse/dependence. Furthermore, there was an association between number of painful body sites and GAD (Gureje et al., 2008). McWilliams et al. (2004) also found stronger associations for GAD compared to panic attacks and major depression in two out of three pain conditions (arthritis and migraine) in the Midlife Development in the United States Survey (MIDUS), even after adjustment for sociodemographic variables and other pain and medical conditions. Moreover, GAD in this study was the mental condition that had the strongest association with multiple pain conditions. In the German Health Survey (GHS), from among a wide range of specific depressive and anxiety disorders, GAD was most strongly associated with clinically significant pain symptoms (Beesdo et al., 2007). Interestingly, all GAD sufferers reported pain and the association seemed to be particularly pronounced with medically unexplained pain symptoms and pain disorder.
In summary, recent findings indicate a strong relationship between GAD and pain syndromes. However, to date, there has been no comprehensive investigation examining the nature and the specificity of this finding. Yet, it is noteworthy that there are a number of observations and a priori assumptions that make the specificity of the association between GAD and pain highly probable.
First, GAD differs from other anxiety disorders in several aspects. GAD has a different incidence pattern characterized by a later high risk period for first onset (mid-teens until later adulthood) (Beesdo, 2006; Bijl, de Graaf, Ravelli, Smit, & Vollebergh, 2002; Kessler et al., 2005; Ruscio et al., 2005). GAD has been described as the most frequent anxiety disorder in the elderly (Beekman et al., 1998). This incidence pattern corresponds with that of chronic pain syndromes which are also notable for onsets until older age (Bellach, Ellert, & Radoschewski, 2000; Elliott, Smith, Penny, Smith, & Chambers, 1999; Eriksen, Jensen, Sjogren, Ekholm, & Rasmussen, 2003; McBeth & Jones, 2007; Torrance, Smith, Bennett, & Lee, 2006). Further, in contrast to some other anxiety disorders with a more variable symptom course, GAD-symptoms – by definition – have to occur almost daily over a time period of at least 6 months, and episodes persist with some waxing and waning of symptoms for many years (Wittchen & Hoyer, 2001). Similar patterns of course have been described for most chronic pain syndromes (Smith, Elliott, Hannaford, Chambers, & Smith, 2004). Therefore, one might expect a closer relationship between pain and GAD than other anxiety disorders.
Second, despite no overlap between pain disorder and GAD in DSM-IV diagnostic criteria, both conditions share some features which would suggest a strong association between both conditions. Among such common features are core cognitive symptoms (such as anxious expectation), some physiological symptoms (such as muscle tension), hypervigilance symptoms (such as sleeping problems, irritability, and restlessness), and behavioral symptoms (such as avoidance). It should be noted that autonomic symptoms were deleted as mandatory diagnostic criteria for GAD in DSM-IV in favour of a list of symptoms that can broadly be characterized as a chronic hypervigilance syndrome. In this respect, GAD differs from the other anxiety disorders which again would suggest a particular relationship to pain.
Third, there are some recent speculations on common psychological and (neuro-)biological mechanisms and pathways in fear/anxiety and pain conditions (Price, 2002), which indicate strong associations between them. Consistent with this, similar pharmacological (Grothe, Scheckner, & Albano, 2004; Gutierrez, Stimmel, & Aiso, 2003) as well as non-pharmacological therapeutic interventions (Borkovec & Ruscio, 2001; Hoyer et al., 2009; Turner-Stokes et al., 2003) seem to work in both GAD and pain patients.
Based on these considerations one would not only expect a significant relationship between pain syndromes and DSM-IV GAD, but also between pain syndromes and generalized anxiety syndromes below the full diagnostic threshold. To our knowledge, such relationships have not been studied. The aim of this current investigation is to use a large, nationally representative population sample to examine: (1) whether medically unexplained pain is more strongly associated with GAD than with other anxiety disorders, (2) whether medically unexplained pain is associated with generalized anxiety below the full diagnostic threshold, and (3) how pain and generalized anxiety occurring together are related to negative outcomes in terms of disability, quality of life, and service utilization. We focus on clinically significant, medically unexplained (somatoform) pain because of indications that particularly unexplained pain may be important in GAD (Beesdo et al., 2007). It should be noted, however, that there is an ongoing controversy surrounding this type of pain classification (Hiller, 2006; Kroenke, 2006; Mayou, Kirmayer, Simon, Kroenke, & Sharpe, 2005; Sharpe, Mayou, & Walker, 2006; Sullivan, 2000; Sykes, 2006). Some (Kroenke, 2006; Mayou et al., 2005; Sharpe et al., 2006) point out the theoretical and practical difficulties in categorizing symptoms to be “medically unexplained (somatoform)” suggesting a simplified categorization and “etiologically neutral” terminology for physical symptoms including pain. Others (Hiller, 2006), in contrast, emphasize the progress that has been made with research on somatoform diagnoses as mental disorders integrating biological, psychological, and social aspects.
Section snippets
Method
The data presented in this paper come from the German National Health Interview and examination survey, mental health supplement (GHS-MHS) conducted in 1998–1999. The survey was approved by the Institutional Review Board of the Robert Koch Institute (Berlin, Germany). All participants provided written informed consent. Aims, design, and methods of the survey have been described in detail elsewhere (Jacobi et al., 2002).
12-Month prevalence of generalized anxiety and pain in the general population
In the prior 12 months, 8.1% of the general population met criteria for PD; an additional 15.4% experienced at least one UPS. The 12-month prevalence rates for threshold GAD, subthreshold GAD, and symptomatic GAD were 1.5%, 2.1%, and 4.2%, respectively. Women were significantly more frequently affected by generalized anxiety and pain at all diagnostic levels (OR range: 1.7–2.7, all p-values < 0.01). Higher rates with older age (age as dimensional variable) were found for DSM-IV threshold GAD only
Discussion
Using 12-month data from a large general population sample we examined the association between medically unexplained pain and GAD as assessed by a standardized diagnostic interview. The major findings emerging from our analyses are: (1) GAD was specifically and more strongly than other anxiety disorders associated with medically unexplained pain, (2) this specific association also applied to subthreshold levels of GAD with some indication of a non-linear dose–response relationship, (3)
Conflict of interest
Dr. Beesdo has received speaking honoraria from Pfizer and travel support from Eli Lilly. Dr. Wittchen has received research support from Eli Lilly, and speaking honoraria from Novartis, and Pfizer. He has been a consult for Eli Lilly, GlaxoSmithKline Pharmaceuticals, Novartis, and Pfizer. Dr. Hoyer, Dr. Jacobi, Dr. Low, and Dr. Höfler have nothing to declare.
Acknowledgments
The German Health Survey (GHS) was supported by grant 01EH970/8 (German Federal Ministry of Research, Education and Science; BMBF). The reported data on mental disorders were assessed in the Mental Health Supplement of the GHS, conducted by the Max-Planck-Institute of Psychiatry, Munich, Germany. Principal investigator was Dr. Hans-Ulrich Wittchen. Reported somatic health status variables come from the GHS-Core Survey, conducted by the Robert Koch-Institute, Berlin, Germany. Principal
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