Recent studies on chronic pain conditions in relation to

Transcription

1 ORIGINAL ARTICLE Chronic Pain Conditions and Suicidal Ideation and Suicide Attempts: An Epidemiologic Perspective Gregory E. Ratcliffe, BSc,* Murray W. Enns, MD, FRCPC,*w Shay-Lee Belik, BSc (Hons),*w and Jitender Sareen, MD, FRCPC*w Objectives: Investigations of the association between chronic pain conditions and suicidal ideation (SI) and suicide attempts (SA) have rarely taken the effect of mental disorders into account and have been limited by nonrepresentative samples. The present study used a large population-based sample to investigate the association between chronic pain conditions and SI and SA. Methods: Data were from the Canadian Community Health Survey Cycle 1.2 public use file conducted by Statistics Canada from 2001 to 2002 (N = 36,984; response rate 77%). Respondents were asked if they had been diagnosed with the following painful conditions: migraine, back problems, arthritis, and fibromyalgia. Respondents were assessed for past 12-month SI and SA. The Composite International Diagnostic Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders-IV. Results: After adjusting for sociodemographics, Axis I mental disorders and comorbidity (3 or more mental disorders), the presence of 1 or more chronic pain conditions was associated with both SI and SA. Among respondents with a mental disorder, comorbidity with 1 or more chronic pain conditions was also associated with SI and SA. In models adjusting for other painful conditions, migraine had the strongest link with SI and SA. Discussion: This is the first study to demonstrate the association between several chronic pain conditions and SI and SA while adjusting for mental disorders in a nationally representative sample. Moreover, this study demonstrates that among individuals with a mental disorder, having a chronic pain condition significantly increased the association with SI and SA. Key Words: chronic pain, suicide attempts, migraine, back problems, arthritis Received for publication February 14, 2007; revised September 17, 2007; accepted September 28, From the *Department of Psychiatry; and wcommunity Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Preparation of this article was supported by (1) a CIHR New Investigator grant awarded to Dr Sareen, (2) a CIHR Canada Graduate Scholarship Master s Award awarded to Ms Belik, and (3) a Western Regional Training Centre studentship funded by Canadian Health Services Research Foundation, Alberta Heritage Foundation for Medical Research, and CIHR awarded to Ms Belik. Reprints: Jitender Sareen, MD, FRCPC, PZ Bannatyne Avenue, Winnipeg, MB, Canada R3E 3N4 ( sareen@cc.umanitoba.ca). Copyright r 2008 by Lippincott Williams & Wilkins (Clin J Pain 2008;24: ) Recent studies on chronic pain conditions in relation to poor overall health, missed days of work, economic burden, and comorbidity of mental disorders have concentrated on 3 particular chronic pain conditions; back problems, migraine, and arthritis. 1 4 Recently, research has also looked at the effect of fibromyalgia (FM) on these issues. 5 7 These chronic pain conditions are highly prevalent in both American and Canadian national surveys (back/neck problems 18.8% to 35.5%, migraine 6.8% to 9.4%, arthritis 6.5% to 16.7%, and FM 0.7% to 3.3%) An expanding body of literature has shown chronic pain conditions to be associated with higher rates of suicidal ideation (SI), suicide attempts (SA), and completed suicides A study of young adults in a Health Maintenance Organization found that the rates of SI and SA were significantly increased in respondents with migraine, after adjusting for the effects of other common mental disorders. 26 A previous study concluded that men were at significantly higher risk of committing suicide during the first 10 years of follow up if they had back pain. 24 Studies have shown an association between abdominal pain and SI and SA. 18,20 Another study found that arthritis was not associated with an increased likelihood of SA. 21 Detailed information on the association between FM and SI and SA is not available in the literature. To the best of our knowledge, only 1 study in the literature has examined the relationship between multiple chronic pain conditions and SI and SA in the same study. The study by Smith et al 27 examined a tertiary pain clinic sample of 153 patients with noncancer pain. The painful conditions assessed in Smith s study were abdominal pain and neuropathic pain, as well the study also looked at pain severity, pain duration, and depression severity. They found that among chronic pain patients, abdominal pain was associated with a 5.5-fold increase in SI and a 4.2-fold increase in SA. In the same study, Smith et al 27 also found that neuropathic pain was associated with a reduced risk of SI and SA. This study found a lack of a strong association between suicidal ideation and pain duration, pain severity, and depression severity. There are 4 main limitations of previous studies on chronic pain. First, the majority of previous studies have 204 Clin J Pain Volume 24, Number 3, March/April 2008

2 Clin J Pain Volume 24, Number 3, March/April 2008 Chronic Pain Conditions and SI and SA used treatment-seeking samples that are limited by selection bias. 18,20,26,27 Second, although the data are strongest for migraine and SI and SA, to date, the majority of the studies have not examined whether there is a differential relationship with SI and SA across painful conditions. 18,20,24,25,27 Thus, determination of which painful conditions are most strongly linked with SI and SA is still required. Third, most studies have not adjusted for multiple mental disorders 18 20,24 27 or for comorbidity of mental disorders 18 21,24 27 ; factors that are known to be associated with both chronic pain conditions 4 and with SI and SA. 28 It remains unclear whether painful conditions are independently associated with SI and SA. Fourth, although migraine conditions in addition to major depression were associated with a higher likelihood of SI and SA compared with those with major depression alone in young adults, 26 it remains unknown whether these results are generalizable to all adults and all painful conditions. To address these limitations, we used a large nationally representative sample of adults to examine the relationship between painful conditions and SI and SA. Four chronic pain conditions were assessed in the survey used for the present study (ie, back problems, migraine, arthritis, and FM). The present study had 2 main objectives. First, we examined whether back problems, migraine, arthritis, and FM had a unique association with SI and SA, independent of mental disorders. Second, we examined whether having a chronic pain condition significantly increased the likelihood of SI and SA among individuals with a mental disorder. METHODS Sample Data were from the Canadian Community Health Survey Cycle 1.2 (CCHS 1.2) public-use file. The CCHS 1.2 is a nationally representative sample (N = 36,984, response rate 77%) conducted by Statistics Canada between 2001 and 2002 of individuals aged 15 years and above living in private dwellings in the 10 provinces, excluding those living in the Canadian territories, on First Nations reserves, or living in institutions. A detailed description of the method for selection of household interviews is reported elsewhere. 29,30 A multistage stratified cluster design was used to ensure the sample would be representative of the Canadian general population. Statistics Canada relied on professional interviewers who received additional training to increase sensitivity on mental health issues. All participants were informed about the nature of the questions before they were asked whether they wished to participate. The majority of the interviews were conducted in person, and telephone interviews were reserved for cases where travel or access was a barrier, or for respondent preference. Chronic pain conditions were assessed in the CCHS 1.2 by asking respondents if they had any long-term conditions, which were expected to last or had already lasted 6 months or more and that had been diagnosed by a health professional. The 4 long-term conditions included in this study were: arthritis or rheumatism, excluding FM; back problems, excluding FM and arthritis (where the interviewer again specifically indicated it must be diagnosed by a health professional); migraine headaches; and FM. This methodology of assessment of physical conditions has been used commonly in epidemiologic studies. 6 Acceptable to good concordance between self-report and medical record measures have been found for chronic conditions in record check studies carried out in conjunction with federal health surveys in both Canada and the United States. 31,32 Suicidal Ideation and Suicide Attempts Respondents in the CCHS 1.2 were asked if they had ever seriously thought about committing suicide or taking their own lives. They were also asked if they had attempted suicide or tried to take their own lives. Both of these questions were followed by the question of whether this thought or experience had occurred in the last 12 months. These questions were used to create the past-year SI and past-year SA variables, respectively. Mental disorders Past 12-month mood disorders (depression and mania), anxiety disorders (panic attack, panic disorder, social phobia, and agoraphobia without panic disorder), and substance dependence (alcohol dependence and drug dependence) were the Diagnostic and Statistical Manual of Mental Disorders-IV assessed in the CCHS 1.2 using the World Health Organization Composite International Diagnostic Interview. 33,34 Sociodemographic Variables Age was measured in number of years and was separated into 4 categories: 15 to 24 years, 25 to 44 years, 45 to 64 years, and 65 years and greater. Education was dichotomized into less than high school and high school or more. Marital status was trichotomized into married/ common law, widowed/separated/divorced, or single. Comorbidity of Mental Disorders A count variable was created of the number of mental disorders experienced by each individual. This was then used to create a binary variable, where individuals with 3 or more mental disorders formed 1 group and individuals with 2, 1, or no mental disorders formed the other group. This comorbidity variable was created on the basis of previous studies, which indicated that having 3 or more mental disorders was strongly associated with lifetime SI and SA. 28,35 Statistical Analyses In all analyses, the appropriate statistical weight was used to ensure that the data were representative of the national population. Standard errors were calculated using the Taylor Series Linearization (TSL) method in the SUDAAN program. 36 Although Statistics Canada r 2008 Lippincott Williams & Wilkins 205

3 Ratcliffe et al Clin J Pain Volume 24, Number 3, March/April 2008 suggests using bootstrapping procedures for variance estimation procedures in the CCHS, we used TSL, because pilot analysis in our laboratory found variance estimates obtained from regression analyses conducted using TSL and bootstrapping to be virtually identical. We examined the relationship between migraine, arthritis, back problems, FM, and 1 or more chronic pain conditions with SI and SA in the whole sample. Multiple logistic regression analyses were used to examine the association between each of the painful conditions and both SI and SA variables. Covariates in the first set of regressions were sociodemographic factors (age, sex, marital status, and education). In the second set of regressions, we included the following covariates: sociodemographics (as noted above), any mood disorder, any anxiety disorder, any substance dependence disorder, and comorbidity of mental disorders. This methodology is similar to previous work by Breslau, 26 which demonstrated that migraine headaches were independently associated with SI and SA after adjusting for the effects of common mental disorders. However, in the current study, we also adjusted for effects of comorbidity of mental disorders, a strong predictor of SI and SA and examined whether nonmigraine painful conditions were independently associated with SI and SA. Finally, because there was significant overlap between the 4 painful conditions, we conducted a regression analysis where each of the 4 painful conditions was entered simultaneously into the same regression to determine the unique association between these painful conditions and SI and SA. In the latter regression, we included covariates of sociodemographic factors, mood disorders, anxiety disorders, substance dependence disorders, and psychiatric comorbidity. Because previous work has shown that migraine headaches may increase the likelihood of SI and SA among individuals with major depression, we conducted analyses among the subsample of respondents meeting criteria for a mental disorder. Similar to the analyses in the whole sample, we conducted 3 sets of regressions: (1) adjusted for sociodemographic factors, (2) adjusted for sociodemographic factors and psychiatric comorbidity, and (3) adjusted for sociodemographic factors, comorbidity, and each of the other painful conditions. RESULTS Table 1 describes the prevalence rates of all the independent and dependent measures used in the current study. Mental disorders, chronic pain conditions, and SI and SA were prevalent in the population. The prevalence of migraine, arthritis, back problems, and FM were 10.7%, 17.5%, 20.9%, and 1.5%, respectively. Table 2 demonstrates the overlap of the 4 chronic pain conditions. Nearly half of the individuals reporting migraine, back problems, or arthritis also endorsed a comorbid chronic pain condition. A much higher proportion of individuals reporting FM endorsed a comorbid chronic pain condition (82.7%) TABLE 1. Independent and Dependent Variables Used in the Current Study * Sex Female 20,211 (50.8) Male 16,773 (49.2) Education High school or more 26,161 (74.5) Less than high school 10,592 (25.5) Marital status Married/common law 19,184 (61.7) Widowed/separated/divorced 7959 (12.8) Single 9798 (25.4) Age 15 to 24 y 5673 (16.5) 25 to 44 y 12,813 (38.0) 45 to 64 y 10,762 (30.5) 65+ yrs 7736 (14.9) Past year mental disorders Any mood disorderw 2122 (5.3) Any anxiety disorderz 1803 (4.8) Any substance dependence disordery 1215 (3.1) Any mental disorder 5782 (14.9) Comorbidity (3 or more mental disorders) 546 (1.3) Current chronic pain conditions Migraine 3984 (10.7) Arthritis or rheumatism 8245 (17.5) Back problems 8397 (20.9) FM 595 (1.5) Any chronic pain 15,317 (37.0) Past year SI and SA Suicidal ideation 1456 (3.7) Suicide attempts 230 (0.5) *All ns are unweighted and all percentages are weighted. wany mood disorder includes major depressive disorder and mania. zany anxiety disorder includes panic attacks, panic disorder, social phobia, and agoraphobia without panic disorder. yany substance dependence include alcohol dependence and drug dependence. Table 3 illustrates that, after adjusting for sociodemographic factors, mental disorders, and comorbidity, there remained a positive association between 1 or more chronic pain conditions and SI [adjusted odds ratio () = 1.46; 95% confidence interval (CI) = ] and SA ( = 1.94; 95% CI = ). Migraine and back problems were also associated with SI and SA. However, arthritis and FM, although associated with SI and SA after adjusting for sociodemographics, were not associated with SI or SA after adjusting for mental disorders. After additionally adjusting for other chronic pain conditions (), there remained a strong positive association between migraine and SI ( = 1.45; 95% CI = ) and SA ( = 1.85; 95% CI = ). The other 3 painful conditions were not associated with SI and SA in this model. Table 4 shows the relationship between painful conditions and SI and SA among respondents with a mental disorder. The data illustrate that comorbidity with 1 or more painful conditions was associated with SI ( = 1.28; 95% CI = ) and SA ( = 1.99; 95% CI = 1.19 to 3.33). Of the chronic pain conditions, the strongest association with SI and SA 206 r 2008 Lippincott Williams & Wilkins

4 Clin J Pain Volume 24, Number 3, March/April 2008 Chronic Pain Conditions and SI and SA TABLE 2. Overlap of Chronic Pain Conditions Of All Those Who Had Migraine (n = 3984)* Arthritis (n = 8245) Back Problems (n = 8397) FM (n = 595) % that also had Migraine 15.2%w 19.2% 36.7% Arthritis 24.8% 34.8% 53.9% Back problems 37.4% 41.4% 52.5% FM 5.0% 4.5% 3.7% % with at least one other conditions 49.5% 49.2% 47.5% 82.7% *All ns are unweighted. wall percentages are weighted. was again with migraine ( = 1.35; 95% CI = and = 2.05; 95% CI = , respectively). The odds of SI and SA among people with a mental disorder were not significantly affected by whether or not the individual reported having arthritis. Individuals with back problems and a mental disorder were at increased odds of having SI ( = 1.36; 95% CI = ) and SA ( = 2.17; 95% CI = ) compared with those with a mental disorder alone. These associations did not remain statistically significant after adjusting for other chronic pain conditions. FM was not significantly associated with SI and SA in this model either. DISCUSSION To the best of our knowledge, this is the first study to examine the association between several chronic pain conditions and SI and SA in a nationally representative sample after adjusting for common mental disorders and comorbidity of mental disorders. The strengths of this study include the use of a very large representative sample, a standardized interview (Composite International Diagnostic Interview) for the diagnosis of mental disorders, and the simultaneous assessment of 4 different kinds of painful conditions. Two main findings are notable from this study. First, the presence of 1 or more chronic pain conditions was uniquely associated with SI and SA (ie, after adjusting for common mental disorders and comorbidity). The present findings in a large community sample extend previous work in treatment-seeking samples. 16,26 These findings suggest the importance of assessment of SI and SA among individuals presenting with painful conditions even in the absence of common mental disorders. The present study demonstrated that among individuals with a mental disorder, comorbidity with 1 or more painful conditions (especially migraine) was associated with SI and SA. These findings suggest that clinicians treating individuals for mental disorders with SI and SA should also carefully assess for chronic pain conditions. Screening for SI and SA among chronic pain patients, especially those with migraine headaches, is also warranted. Second, among the 4 chronic pain conditions examined in the current study, migraine was most highly associated with SI and SA in the whole sample and in individuals with a mental disorder. To the best of our knowledge, the current study is the first to test whether there is a differential relationship between painful conditions and SI and SA. In keeping with previous work, we found a strong association between migraine and SI and SA, 26 and a lack of association between arthritis and SI and SA when adjusting for mental disorders. 21 Similar to arthritis, FM was significantly associated with SI and SA after adjusting for sociodemographics, but not after adjusting for mental disorders. We found associations between back problems and SI and SA; however, these associations did not remain significant after adjusting for other painful conditions. Thus, clinicians need to carefully assess for SI and SA among individuals with chronic pain conditions. In the absence of mental disorders, it seems that individuals with migraine, FM, and back problems still need proper SI and SA assessment. Because of the cross-sectional nature of the current findings, a causal relationship between painful conditions and SI and SA cannot be inferred. However, there are a number of possible explanations for this relationship. First, direct effects may be present such that individuals suffering with high levels of chronic pain may seek escape from their suffering by considering or attempting suicide. 16 Second, indirect mechanisms may exist whereby painful conditions, specifically migraine, may increase the likelihood of another condition (eg, mental disorders, insomnia), which in turn leads to SI and SA. 4,26,28,37 43 The current findings support this hypothesis, because the odds of association between painful conditions and SI and SA were reduced when mental disorders were included in the model when compared with models that did not include mental disorders. Similar to findings of Breslau, 26 the current study also supports the independent association between chronic pain conditions and SI and SA. A recent review 16 suggested that insomnia might be an indirect mechanism by which chronic pain is associated with SI and SA. Further investigations examining the effects of insomnia on the relationship between chronic pain and SI and SA are required to determine if this is a possible link. r 2008 Lippincott Williams & Wilkins 207

5 Ratcliffe et al Clin J Pain Volume 24, Number 3, March/April 2008 TABLE 3. SI and SA in Relation to Chronic Pain Conditions in the Whole Sample (n = 36,984) SI SA Chronic Pain Condition Chronic Pain Condition Absent Present Absent Present w Physical Conditions 1122 (3.3) 334 (7.3) 2.27 ( )*** 1.52 ( )*** 1.45 ( )** 157 (0.4) 73 (1.7) 3.65 ( )*** 2.10 ( )** 1.85 ( )* Migraine (n = 3984) 1105 (3.5) 347 (4.4) 1.70 ( )*** 1.19 ( ) 1.10 ( ) 174 (0.5) 55 (0.6) 2.48 ( )*** 1.47 ( ) 1.20 ( ) Arthritis (n = 8245) 960 (3.3) 494 (5.2) 1.86 ( )*** 1.25 ( )* 1.17 ( ) 140 (0.4) 88 (0.9) 2.97 ( )*** 1.63 ( )* 1.45 ( ) Back problems (n = 8397) FM (n = 595) 1405 (3.6) 48 (8.0) 2.34 ( )*** 1.43 ( ) 1.21 ( ) 220 (0.5) 10 (1.5) 3.12 ( )** 1.72 ( ) 1.27 ( ) 662 (2.9) 793 (5.0) 2.13 ( )*** 1.46 ( )*** NA 91 (0.3) 139 (0.9) 3.65 ( )*** 1.92 ( )** NA Any chronic pain (n = 15,203) wall ns are unweighted and all percentages are weighted. indicates adjusted odds ratio, adjusted for sex, age, marital status, and education;, adjusted odds ratio, adjusted for sex, age, marital status, education, any mood disorder, any anxiety disorder, any substance dependence disorder, and comorbidity (3 or more mental disorders);, adjusted odds ratio, adjusted for sex, age, marital status, education, any mood disorder, any anxiety disorder, any substance dependence disorder, comorbidity (3 or more mental disorders), and other chronic pain disorders (arthritis, back problems, and migraine); NA, cell not applicable. *P<0.05. **P<0.01. ***P< A common or shared factor may also explain the comorbidity between chronic pain and SI and SA. 24,26 One possible theory involves the neurotransmitter serotonin. 26 Studies have suggested that abnormalities of the serotonergic system are related to SI and SA, as well as migraine This theory is also of special interest, because it could be used to explain the stronger association between SI and SA with migraine, as compared with other chronic pain disorders. Other factors requiring further investigation include the quality and quantity of the pain experienced (ie, duration, intensity, disability). Current findings should be interpreted with 6 specific limitations in mind. First, as mentioned previously, the cross-sectional nature of the data precludes determination of causality. Also, because the chronic condition variables were defined as current and the SI and SA variables were past-year, it is possible that chronic pain conditions may have occurred at a separate time point from the SI or SA. Our analyses allow associations to be made, but prospective studies would be needed to better address whether chronic pain conditions are risk factors for development of SI and SA. Second, chronic noncancer pain conditions were determined on the basis of self-report diagnosis data rather than physician diagnosis. A review of medical records or a physician assessment would improve the expected errors in self-report diagnosis. However, previous work has demonstrated acceptable concordance between self-report endorsement of physical disorders and medical records. 9 Third, the presence of aura with respect to migraine was not assessed in the survey. Breslau 26 showed a relationship between migraine with aura and SI and SA specifically, an issue that this manuscript has been unable to address. Future studies should examine whether the subtypes of migraine have differential associations with SI and SA. Fourth, a range of other mental disorders that are known to be associated with SI and SA 28 were not assessed in the survey, such as personality disorders, schizophrenia, 51 and posttraumatic stress disorder, 52 which may have affected the associations between the chronic pain conditions and SI and SA. A study with a more thorough assessment of mental disorders could address this limitation. Fifth, although SI and SA are linked with completed suicide, 53 the current study cannot comment on whether chronic pain conditions are associated with completed suicides. Future studies using a psychologic autopsy design should assess for chronic pain conditions among those who have completed suicide. Sixth, chronic abdominal pain and tension nonmigraine headaches were not assessed in the CCHS 1.2. These painful conditions are common in the general population and may also be associated with SI and SA. Future studies are required to examine whether the present findings of the strong association between migraine headaches and SI and SA remain after adjusting for chronic abdominal pain and nontension headaches. The above factors limit the extent to which conclusions can be reached from the data presented and 208 r 2008 Lippincott Williams & Wilkins

6 Clin J Pain Volume 24, Number 3, March/April 2008 Chronic Pain Conditions and SI and SA TABLE 4. SI and SA in Relation to Chronic Pain Conditions in the Subsample of Respondents With a Mental Disorder (n = 5782) SI SA Chronic Pain Condition Chronic Pain Condition Absent Present Absent Present w Physical Conditions Migraine 642 (13.3) 256 (19.1) 1.56 ( )*** 1.38 ( )* 1.35 ( )* 110 (1.9) 62 (5.3) 2.73 ( )*** 2.34 ( )** 2.05 ( )** Arthritis 679 (14.2) 216 (14.9) 1.06 ( ) 0.89 ( ) 0.82 ( ) 130 (2.4) 41 (3.0) 1.65 ( ) 1.54 ( ) 1.23 ( ) Back problems 551 (13.3) 345 (16.9) 1.36 ( )* 1.15 ( ) 1.13 ( ) 97 (2.1) 73 (3.7) 2.17 ( )*** 1.59 ( ) 1.37 ( ) Fibromyalgia 856 (14.2) 39 (20.7) 1.54 ( ) 1.55 ( ) 1.47 ( ) 162 (2.5) 10 (5.0) 2.37 ( )* 2.28 ( ) 1.64 ( ) 360 (12.3) 537 (16.6) 1.50 ( )*** 1.28 ( )* NA 60 (1.7) 112 (3.5) 2.65 ( )*** 1.99 ( )** NA Any chronic pain condition wall ns are unweighted and all percentages are weighted. indicates adjusted odds ratio, adjusted for sex, age, marital status, and education;, adjusted odds ratio, adjusted for sex, age, marital status, education, and comorbidity (3 or more mental disorders);, adjusted odds ratio, adjusted for sex, age, marital status, education, comorbidity (3 or more mental disorders), and other chronic pain disorders (arthritis, back problems, and migraine); NA, cell not applicable. *P<0.05. **P<0.01. ***P< calls for more investigation into these relationships. Prospective studies that include physician-diagnosed chronic pain conditions and all mental disorders linked to suicide are needed to determine if chronic pain conditions, in and of themselves, do indeed lead to completed suicides. In conclusion, the current study demonstrated that, as a group of physical conditions, chronic pain conditions were prevalent among those with SI and SA in a large community sample. We also found that migraine was independently associated with SI and SA, even after adjusting for mental disorders and comorbidity of mental disorders. Furthermore, the current study demonstrated that among individuals with mental disorders, migraine and back problems significantly increased the frequency of SI and SA. These findings underscore the importance of assessment of SI and SA among the individuals presenting with painful conditions. REFERENCES 1. Bolten W, Kempel-Wailbel A, Pforringer W. Analysis of the cost of illness in backache. Med Klin (Munich). 1998;93: Becker N, Thomsen AB, Olsen AK, et al. Pain epidemiology and health-related quality of life in patients with chronic non-malignant pain. Ugeskr Laeger. 1998;160: Eriksen J, Jensen MK, Sjogren P, et al. Epidemiology of chronic non-malignant pain. Pain. 2003;106: McWilliams LA, Goodwin RD, Cox BJ. Depression and anxiety associated with three pain conditions: results from a nationally representative sample. Pain. 2004;111: Bombardier CH, Buchwald D. Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health-care use. Med Care. 1996;34: Robinson RL, Birnbaum HG, Morley MA, et al. Economic cost and epidemiologic characteristics of patients with fibromyalgia claims. J Rheumatol. 2003;30: Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 2006; 67: Patten SB, Williams JV, Wang J. Mental disorders in a population sample with musculoskeletal disorders. BMC Muscoloskelet Disord. 2006;7: Kessler RC, Ormel J, Demler O, et al. Comorbid mental disorders account for the role impairment of commonly occurring chronic physical disorders: results from the National Comorbidity Survey. J Occup Environ Med. 2003;45: Stang PE, Brandenburg NA, Lane MC, et al. Mental and physical comorbid conditions and days in role among persons with arthritis. Psychosom Med. 2006;68: Stein MB, Cox BJ, Afifi TO, et al. Does co-morbid depressive illness magnify the impact of chronic physical illness? A population-based perspective. J Psychol Med. 2006;36: Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arth Rheum. 1995;38: Prescott E, Kjoller M, Jacobsen S, et al. Fibromyalgia in the adult Danish population: I. A prevalence study. Scand J Rheumatol. 1993; 22: Makela M, Heliovaara M. Prevalence of primary fibromyalgia in the Finnish population. Br Med J. 1991;303: White KP, Speechley M, Harth M, et al. The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol. 1999;26: Tang NK, Crane C. Suicidality in chronic pain: a review of the prevalence, risk factors and psychological links. Psychol Med. 2006;36: r 2008 Lippincott Williams & Wilkins 209

7 Ratcliffe et al Clin J Pain Volume 24, Number 3, March/April Stenager EN, Stenager E, Jensen K. Attempted suicide, depression, and physical disease: a 1-year follow-up study. Psychother Psychosom. 1994;61: Hinkley BS, Jaremko ME. Effects of pain duration on psychosocial adjustment in orthopedic patients: the importance of early diagnosis and treatment of pain. J Pain Symptom Management. 1994;9: Hitchcock LS, Ferrell BR, McCaffery M. The experience of chronic nonmalignant pain. J Pain Symptom Manage. 1994;9: Treharne GJ, Lyons AC, Kitas GD. Suicide ideation in patients with rheumatoid arthritis. Research may help identify patients at high risk. Br Med J. 2000;320: Goodwin RD, Marusic A, Hoven CW. Suicide attempts in the United States: the role of physical illness. Soc Sci Med. 2003;56: Fishbain DA, Goldberg M, Rosomoff RS, et al. Completed suicide in chronic pain. Clin J Pain. 1991;7: Fishbain DA. The association of chronic pain and suicide. Semin Clin Neuropsychiatry. 1999;4: Penttinen J. Back pain and risk of suicide among Finnish farmers. Am J Public Health. 1995;85: Magni G, Rigatti-Luchini S, Fracca F, et al. Suicidality in chronic abdominal pain: an analysis of the Hispanic Health and Nutrition Examination Survey (HANES). Pain. 1998;76: Breslau N. Migraine, suicidal ideation, and suicide attempts. Neurology. 1992;42: Smith MT, Edwards RR, Robinson RC, et al. Suicidal ideation, plans, and attempts in chronic pain patients: factors associated with increased risk. Pain. 2004;111: Kessler RC, Borges G, Walters EE. Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey. Arch Gen Psychiatry. 1999;56: Gravel R, Beland Y. The Canadian Community Health Survey: mental health and well-being. Can J Psychiatry. 2005;50: Bailie L, Dufour J, Hamel M. Data quality assurance for the Canadian Community Health Survey. Stat Can Edwards WS, Winn DM, Kurlantzick V, et al. Evaluation of national health interview survey diagnostic reporting. Vital Health Stat Z. 1996;122: Baker S, Stabile M, Deri C. What do self-reported, objective, measures of health measure? J Hum Resour. 2001;39: Kessler RC, Ustun TB. The World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Int J Methods Psychiatr Res. 2004;13: Kessler RC, Wittchen H-U, Abelson JM, et al. Methodological studies of the Composite International Diagnostic Interview (CIDI) in the US National Comorbidity Survey (NCS). Int J Methods Psychiatr Res. 1998;7: Wunderlich U, Bronisch T, Wittchen HU. Comorbidity patterns in adolescents and young adults with suicide attempts. Eur Arch Psychiatry Clin Neurosci. 1998;248: Shah BV, Barnswell BG, Bieler GS. SUDAAN User s Manual: Software for Analysis of Correlated Data. Research Triangle Park, NC: Research Triangle Institute; Henriksson MM, Aro HM, Marttunen MJ, et al. Mental disorders and comorbidity in suicide. Am J Psychiatry. 1993;150: ten Have M, Vollebergh W, Bijl R, et al. Bipolar disorder in the general population in The Netherlands (prevalence, consequences and care utilisation): results from The Netherlands Mental Health Survey and Incidence Study (NEMESIS). J Affect Disord. 2002;68: Verona E, Sachs-Ericsson N, Joiner TE Jr. Suicide attempts associated with externalizing psychopathology in an epidemiological sample. Am J Psychiatry. 2004;161: Phillips MR, Yang G, Li S, et al. Suicide and the unique prevalence pattern of schizophrenia in mainland China: a retrospective observational study. Lancet. 2004;364: Black DW, Warrack G, Winokur G. The Iowa record-linkage study. Suicides and accidental deaths among psychiatric patients. Arch Gen Psychiatry. 1985;42: Sareen J, Jacobi F, Cox BJ, et al. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med. 2006;166: Currie SR, Wang J. Chronic back pain and major depression in the general Canadian population. Pain. 2004;107: Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry. 1976; 33: Brunner J, Bronisch T. Neurobiological correlates of suicidal behavior. Fortschr Neurol. 1999;67: Pandey GN, Pandey SC, Dwivedi Y, et al. Platelet serotonin-2a receptors: a potential biological marker for suicidal behavior. Am J Psychiatry. 1995;152: Escriba PV, Ozaita A, Garcia-Sevilla JA. Increased mrna expression of alpha2a-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims. Neuropsychopharmacology. 2004;29: Villalon CM, Centurion D, Valdivia LF, et al. Migraine: pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003;1: Srikiatkhachorn A, Govitrapong P, Limthavon C. Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed migraine. Headache. 1994;34: Purselle DC, Nemeroff CB. Serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacology. 2003;28: Cavanagh JT, Carson AJ, Sharpe M, et al. Psychological autopsy studies of suicide: a systematic review. Psychol Med. 2003;33: Sareen J, Houlahan T, Cox BJ, et al. Anxiety disorders associated with suicidal ideation and suicide attempts in the National Comorbidity Survey. J Nerv Ment Dis. 2005;193: Suominen K, Isometsa E, Suokas J, et al. Completed suicide after a suicide attempt: a 37-year follow-up study. Am J Psychiatry. 2004;161: r 2008 Lippincott Williams & Wilkins