bs_bs_banner

Pain Medicine 2014; 15: 1835–1849 Wiley Periodicals, Inc.

Review Article The Pain Suicidality Association: A Narrative Review

David A. Fishbain, MD, FAPA,*†‡§¶ John E. Lewis, PhD,* and Jinrun Gao, MS, MBA¶ Departments of *Psychiatry, †Neurological Surgery, and ‡Anesthesiology, Miller School of Medicine, University of Miami, Miami, Florida; §Department of Psychiatry, Miami VA Medical Center, Miami, Florida; ¶ State Farm Insurance, Bloomington, Illinois, USA Reprint requests to: David A. Fishbain, MD, FAPA, Department of Psychiatry, Miller School of Medicine, U Health Psychiatry, University of Miami, 1695 NW 9th Avenue, Suite 33026, Miami, FL 33136, USA. Tel: 305-335-9021; Fax: 305-668-0578; E-mail: [email protected]. None of the authors had any direct or indirect funding in support of this study.

Results. The following groups of studies received an A consistency rating (consistent evidence from multiple studies): SI, SA, and SC for other than APPs/CPPs; and SI, SA, and SC for CPP prevalence greater than an appropriate control group. Also, a subgroup of the SI, SA, and SC studies for other than APPs/CPPs had controlled for behavioral issues (potential confounders). These three subgroups also received an A consistency rating. The 58 studies also identified a number of new predictor variables for SI, SA, and SC in CPPs. Conclusions. These studies solidify the evidence for an association between pain and SI, SA, and SC in both CPPs and other than APPs/CPPs. Key Words. Suicidality; Suicide Ideation; Suicide Attempts; Suicide Completion; Pain; Chronic Pain; Acute Pain; Review; Chronic Pain Patients; Acute Pain Patients

Abstract Objectives. The objective of this narrative review was to examine recent evidence and, when necessary, past evidence on the association between pain and suicidality. Design. Fifty-eight research reports were found on this topic, which had not previously been reviewed. These reports were divided into groups by whether they addressed suicide ideation (SI), suicide attempts (SAs), or suicide completion (SC), and what population they represented (acute pain patients [APPs], chronic pain patients [CPPs], other than APPs/CPPs) and whether they controlled for relevant confounders. Information as to whether the results of these studies supported/did not support the association of pain and suicidality was abstracted. For each group of studies (above), a vote counting method was utilized to determine the overall percentage of studies supporting/not supporting the association of pain and suicidality. According to this percentage, the consistency of the data supporting this association was rated according to Agency for Healthcare Research and Quality guidelines.

Introduction At the present time, the relationship between chronic pain (CP) and suicidality is of significant concern to the pain clinician. Early non-CP literature [1–8] indicated that there may be a relationship between CP and suicidality. Perhaps, in response to this literature or as a general approach to the evaluation of depression, a major early textbook on pain contained a chapter on pain and depression. Here, a discussion on the importance of evaluating pain patients for suicidality was presented, although no evidence was referenced for this association (Ward NG, Pain and Depression, Chapter 18 in The Management of Pain, Bonica Editor, 1990). The first pain literature report on this association appeared in 1991. Here, in a long-term follow-up study (6 months to 1 year) of 2,146 chronic pain patients (CPPs) treated at a pain center, but not currently under that pain center’s care, it was discovered that three patients had completed suicide [9]. The suicide rate for this CPP population was calculated and statistically compared with the US general population. The CPP suicide rate was found to be significantly greater than that of the general population (two to three times). Subsequent pain reports [10–19] also appeared to link CP and suicidality. 1835

Fishbain et al. This literature was subsequently reviewed [20]. The conclusions of this review were that suicide ideation (SI), suicide attempts (SAs), and suicide completions (SCs) appeared to be commonly found in CPPs and that CP may be a suicide risk factor [20]. As a result of this research in 2003, the American Psychiatric Association included CP as a risk factor for SC in their guidelines for the assessment and treatment of patients with suicidal behavior [21]. In 2006, Tang and Crane [22] again reviewed this literature as six new studies [23–28] had been added. They reported that the prevalence of SI within CPPs was approximately 20%, lifetime prevalence of SA was between 5% and 14% and that relative to controls, the risk of death by suicide appeared to be at least double in CPPs [22]. They also reported that the reviewed studies identified six risk factors or predictors of suicidality in CPPs: type/intensity/duration of pain, sleep onset insomnia, helplessness/hopelessness in reference to pain, desire to escape from pain, pain catastrophizing/ avoidance, and problem-solving deficits [22]. Finally, in 2007, Spiegel et al. [29] reviewed eight studies on the association of chronic abdominal pain and suicidality. Chronic abdominal pain was found to be an independent predictor of suicidality after adjusting for comorbid psychiatric conditions [29]. The narrative structured review described below is an update on this literature and is necessary for a number of reasons. These are the following. Firstly, a significant amount of time has passed since the last review during which a significant number of studies on suicidality and pain have been added to this literature (specifically 58). Secondly, the previous literature is of itself was not convincing as to whether pain was actually associated with SCs in CPPs and non-CPPs, as SCs are extremely rare, resulting in few studies. Thirdly, the previous literature was not clear as to whether the association of pain and suicidality was relevant to different subgroups, such as veterans with pain, geriatric patients with pain, acute pain patients (APPs), etc. Fourthly, the previous literature had few studies where CPPs were compared with controls for suicidality. Fifthly, the previous literature had identified a limited number of risk factors (predictors) for suicidality in CPPs. More studies in this area are, however, needed as there is still limited information as to which patients are at greater risk for SC. Sixthly, the previous literature contained few studies where the information was gathered prospectively, and there were controls for psychiatric/ behavioral issues that have a great impact on suicidality. Seventhly, the previous literature contained few studies on specific pains such as neuropathic pain. Eighthly, recent reports of opioid overdoses have had caused a reaction within the medical community, causing reduced access to pain treatment with opioids. This in turn may be causing an increase in suicidality in CPPs unable to get adequate care. Lastly, the study on the association between pain and suicidality has recently become a priority issue for the Veterans Administration. 1836

The three previous reviews [20,22,29] of this literature were narrative reviews that did not utilize any systemic methods. The review described below, although a narrative nonsystemic review, used some systemic methods to gather data. In addition, it utilized a vote counting method to determine whether the reviewed studies supported/did not support the association of pain and suicidality. It then utilizes the Agency for Healthcare Research and Quality (AHRQ) guidelines [30] to rate the overall consistency of this evidence based on the percentage of studies supporting this potential association. To our knowledge, it is the first such review of the pain/suicidality literature. Methods Relevant references were located by the following procedure. MEDLINE, Embase, AMED, Psychological Abstracts, Science Citation Index, and the National Library of Medicine Physician Data Query databases were reviewed utilizing the following subject headings: pain, chronic pain, chronic pain patients, acute pain, low back pain, chronic low back pain, failed back surgery syndrome, soft tissue syndromes, fibromyalgia, fibromyalgia syndrome, musculoskeletal pain, chronic widespread pain, myofascial pain, and myofascial pain syndrome. Each of these was exploded with suicide, suicide completion, suicide attempts, and suicide ideation, and all retrieved references reviewed. The searches were not restricted to the English language and conducted back to 1966, except for Science Citation index, which was conducted back to 1974. The upper limit of each search was March 2013. A manual search was also performed using key pain journals, pain meeting abstracts, and textbooks. For the following journals, the following years were reviewed: Pain, 1975–March 2013; Spine. 1986–March 2013; The Pain Clinic, 1986–March 2013; Clinical Journal of Pain, 1985– March 2013; Pain Medicine, 2000–March 2013. Abstracts of the following meetings were reviewed for the following years: International Association for the Study of Pain 1981, 1984, 1987, 1990, 1993, 1996, 1999, 2002, 2005, 2008, 2011 and the American Pain Society Meetings 1982–2013. One thousand six hundred and nineteen references were found and subjected to a cursory review. Studies were excluded from detailed review for the following reasons: 1) did not address acute or CP; 2) did not address SI, SA, or SC; and 3) the report was not a study, e.g., case reports. Previously reviewed studies and case reports were placed into a separate file. Studies were included for detailed review if they were not excluded by the above exclusion criteria. Of the original 1,619 references, 1,561 were excluded by this process or had been previously reviewed, leaving 58 studies that fulfilled these exclusion/inclusion criteria. These 58 studies [31–88] were reviewed in detail and sorted into seven lines of evidence: SI and pain by type of populations; SA and pain by type of population; SC and pain by type of populations; reported prevalence

The Association of Pain and Suicidality percentages of SI in CPPs and reported prevalent SI vs controls; reported prevalence percentages of SA in CPPs and reported prevalence of SA in CPPs vs controls; reported prevalence percentages of SC in CPPs and reported prevalence of SC in CPPs vs controls; and reported prevalence percentages of SI and SA in APPs vs controls. Studies were also scrutinized for variables that were demonstrated to independently predict SI, SA, or SC in CPPs and APPs. Reported predictors were recorded. Data from the above lines of evidence were then abstracted into seven Appendix tables (Tables A1–7) and labeled according to those lines of evidence. Whether each study did/did not support the association between pain and suicidality was placed into the table as a “Yes” vote. The senior author independently abstracted the data into Tables A1–7. The studies were not rated for quality as this was not meant to be a systemic review. The senior author also categorized the type of evidence the studies represented in Tables A1–7. This was based on the guidelines developed by the AHRQ for categorizing the levels of evidence represented by the reviewed studies (Table A8, Subsection I) [30]. Studies were categorized I through V according to this scheme. The percentage of studies supporting the association of pain and suicidality was than calculated for each table according to the Yes votes. The overall strength and consistency of the research evidence represented by the percentage of studies supporting the association between pain and suicidality (the Yes votes) (Tables A1– 7 ) were then rated according to the AHRQ consistency of evidence guidelines (Table A8, Subsection II) [30]. These guidelines allow the researcher to categorize the reviewed evidence as being consistent, generally consistent, inconsistent, or demonstrating little or no evidence for the question associated with the studies in each table. To render a consistency rating, one needs to have at least three studies that address the issue under study. As such, for this review, if there were not enough studies within the 58 studies that addressed the issue in question, studies from the previously reviewed literature were added in order to have a reliable consistency rating. As a final step, data from Tables A1–7 were formatted into a summary table (Table 1). This table was designed to summarize the overall findings of this narrative structured review. The headings for these tables are the following: table number, line of evidence, number of studies in this group, % of studies in the group with each type of evidence category, and strength and consistency of this evidence for the line of evidence addressed by the studies in that table according to AHRQ consistency guidelines. If it was necessary to tap previously reviewed studies, this was noted in the table.

Results The results of this structured review from Tables A1–7 are summarized in Table 1. These results were as follows: For SI and pain by type of population (25 studies, Table A1), of the four types of studies (including those that were controlled for behavioral issues), three received an A consistency rating for an association between SI and pain. The fourth type of study group (prospective) did not have enough studies for a consistency rating, but all three studies in this group indicated an association. Of all studies combined (N = 25), 23 studies or 91.7% supported this association for an A consistency rating. For SA and pain by type of population (eight studies, Table A2), of the four types of study groups, one received an A consistency rating for an association between SA and pain. The two other study types (prospective and Type 3) did not have enough studies for a consistency rating. Of all studies combined (N = 8), five studies or 87.5% supported this association for an A consistency rating. For SC and pain by type of population (nine studies, Table A3), of the four types of study groups, three received an A consistency rating for an association between SC and pain. The fourth type of study group (prospective) did not have enough studies for a consistency rating, but of the two studies in this group, 100% supported an association. Additionally, previously reviewed literature contained two prospective studies that were added to the two prospective SC studies in this review. This gave a total of four studies, all of which indicated an association between pain and SC for an A consistency rating. Of all studies combined (N = 9), eight or 88.8% supported this association for an A consistency rating. For reported prevalence of SI in CPPs and reported prevalence of SC in CPPs vs controls (10 comparisons, Table A4), 80.0% of the comparisons supported an association between CP and SI (consistency A). SI prevalence in CPPs ranged from 7.92% to 40.9%. For the prevalence of SA in CPPs vs controls (Table A5), there were only three studies, 100% of which supported an association between CP and SA. The number of studies here was not enough for a consistency rating. However, the previously reviewed literature contained three studies [11,15,89] that had utilized a control group for SA. All three of these studies had demonstrated a greater prevalence of SA in CPPs vs controls. This made a total of six studies, 100% of which showed a statistically greater prevalence of SA within CPPs vs controls for an A consistency rating. History of SA ranges from 14.1% to 38% (different for men and women). For the prevalence of SC in CPPs vs controls (Table A6), there was only one study with a comparison group, 1837

Fishbain et al.

Table 1

Consistency of each line of evidence for Appendix Tables A1–7

Table Number, Line of Evidence, Number of Studies in Group

% of Studies in Group for Each Type of Evidence Category

Strength and Consistency of Each Line of Evidence Addressed by the Studies according to AHRQ Consistency Guidelines

Suicide ideation and pain by type of population; 25 studies (Table A1) [37–47,62,65–67, 72,74–80,82,83]

Type 3; five studies or 20%

• Of Type 3 (five studies), 80% supported an association between SI and pain (Consistency A). • Of Type 4 (20 studies), 100% supported an association between SI and pain (Consistency A). • Of Type 3 (prospective) (three studies), 100% supported an association between SI and pain (Consistency unknown [small number of studies]). • Of Type 3 and 4 (controlled for behavioral variables) (11 studies), 90.9% supported an association between SI and pain (Consistency A).

Type 4; 20 studies or 80% Type 3 (prospective); three studies or 12% Type 3 and 4 controlled for behavioral variables; 11 studies or 44%

Suicide attempts and pain by type of population; eight studies (Table A2) [38,44–46, 50,63,69,71,81]

Type 3; two studies or 25% Type 4; six studies or 75%

Type 3 (prospective); one study or 12.5% Type 3 and 4 (controlled for behavioral variables); seven studies (62.5%)

Suicide completions and pain by type of population; nine studies (Table A3) [31–35,56, 60,68,71]

Type 3; five studies or 55.5% Type 4; four studies or 44.4% Type 3 (prospective); two studies or 22.2%

Type 3 and 4 controlling for behavior variables; three studies or 33.3%

Prevalence percentages of SI in CPPs vs controls; 6 studies but 1 with 5 comparisons, making total 10 comparisons (Table A4) [49,54,55,61,64,70, 75,84–88,100] Prevalence percentages of SA in CPPs vs controls; three studies (Table A5) [48,55,73]

Type 3; six studies or 100%

Prevalence percentages of suicide completions in CPPs vs control; one study (Table A6) [58]

Type 3; one study or 100%

Reported prevalence of SI and SA in APPs vs controls; two studies (Table A7) [54,55]

Type 3 with control group; two studies or 100% for SI (actually six comparisons), Type 3 with control group; one study or 100% for SA

Type 3; three studies or 100%

• For all studies combined, 91.7% supported an association between SI and pain (Consistency A). • Of Type 3, 100% supported an association between SA and pain (consistency unknown as not enough studies). • Of Type 4, 83.3% supported an association between SA and pain (Consistency A [One study {50} could not be counted in either direction as association was not addressed]). • Of Type 3 (prospective), the one study supported an association between SA and pain (consistency unknown [small number of studies]). • Of Type 3 and 4 (controlled for behavioral variables), 80% supported an association between SA and pain (Consistency A). • For all studies combined, 87.5% supported an association between SA and pain (Consistency A). • Of Type 3, 80% supported the association between SC and pain (Consistency A). • Of Type 4, 100% supported the association between SC and pain (Consistency A). • Of Type 3 (prospective), 100% supported the association between SC and pain (consistency unknown [not enough studies]). However, in the previously reviewed literature, there were two studies [8,17] that were prospective in nature. Both studies showed an association between SC and pain. As such, for this category, there were four studies, 100% of which showed an association between SC and pain (Consistency A). • Of Type 3 and 4, controlling for behavior variables, 100% supported the association between SC and pain (Consistency A). • For all studies combined, 88.8% supported an association between SC and pain (Consistency A). • Of Type 3, of 6 studies, all with control group for 10 comparisons, 8 comparisons or 80% supported an association between SI and pain (Consistency A). • SI prevalence in CPP ranged from 7.92% to 40.9% and was 4.4% for homicide–suicide ideation.

• Of Type 3, all with control group, 100% supported an association between history of SA and CP (consistency unknown as there were only three studies). However, in the previously reviewed literature, there were three studies [11,15,89] that had utilized a control group for SA. All three of these studies had demonstrated a greater prevalence of SA in CPPs vs controls. This made a total of six studies, 100% of which had a statistically greater prevalence of SA within CPPs vs controls (Consistency A). • History of SA ranged from 14.1% to 38% (different men and women). • Of Type 3, all with control group (one study) [58], 100% suggested an association between SC and CP (consistency unknown as there was only one study). However, the previously reviewed literature contained three studies [9,16,28] that had a comparison group for SC. All three of these studies had demonstrated a statistical difference between CPP and controls. This gave a total of four studies, 100 % of which indicated a statistical difference (Consistency A). • Of Type 3, all with control group for SI (two studies) but with six comparisons, 100 % supported an association between SI and acute pain—of these, all 6 types of SI supported this association (Consistency A). • Of Type 3 with control group, for SA (one study), or 100% supported an association between SA and acute pain (consistency unknown).

AHRQ = Agency for Healthcare Research and Quality; APP = acute pain patient; CP = chronic pain; CPP = chronic pain patient; SA = suicide attempt; SC = suicide completion; SI = suicide ideation.

resulting in an unknown consistency rating. That study indicated an association between CP and SC. However, previously reviewed literature contained three studies [9,16,28] where CPPs had been compared for SC with 1838

control groups. All three of these studies demonstrated a greater prevalence of SC within CPPs. This gave a total of four studies, 100% of which demonstrated this association for an A consistency rating.

The Association of Pain and Suicidality For the prevalence of SI in APPs vs controls (Table A7), 100% supported the association of SI and acute pain, leading to an A consistency rating. For the prevalence of SA in APPs vs controls (Table A7), there was only one study with one comparison, leading to an unknown consistency rating. However, that study indicated an association. The reviewed studies indicated that the following variables were predictors for SI in CPPs. Demographic variables were age [85], sex [85], worker compensation status [36], and in litigation [36]. Pain-related variables were pain severity [85], pain duration [57,85], pain catastrophizing [85], degree of pain-related catastrophizing [88], and pain status [36]. Health-related variables were functional limitation [85], patient health questionnaire scores [85], disability perception [84], and smoking [53]. Psychiatric/behavioral variables were history of sexual/physical abuse [86], family history of depression [86], social withdrawal [86], Behavioral Health Inventory 2 (BHI-2) Borderline Scale scores [84], magnitude of depression [88], and the Interpersonal Relationship Scale scores [85]. Patient perception variables were treated unfairly by family [84], thoughts of revenge killing [54], motivated to seek revenge [54], selfperceived burdensomeness [52,85,87], and BHI-2 Doctor Dissatisfaction scale scores [54]. The reviewed studies also found the following variables to be predictors for SA in CPPs. One demographic variable was age greater than 35 [50]. Psychiatric variables were BHI-2 survival of violence scale scores [55], hearing voices others do not hear [55], lots of energy [55], and no misuse of alcohol (this last predictor appears to be counterintuitive.). For SA in fibromyalgia pain, the following psychiatric variables were predictive: poor sleep quality, anxiety, and depression [51]. The only predictor for SC in CPPs that was reported was that of the diagnosis of fibromyalgia [59], but for females only. In APPs, the following variables were reported to be predictors of SI. Psychiatric variables were a depression item [55], a borderline item [55], a hostility item [55], anger [55], a family dysfunction item [55], and scores on the BHI-2 Family Dysfunction Scale [84]. Health-related variables were disability perception [84], scores on the BHI-2 somatic complaints scale [55], a somatic complaints item [55], and a muscular bracing item [55]. For SA in APPs, the following variables were reported to be predictors. Demographic variables were worker compensation status [36], history of personal injury [36], and in litigation [36]. Psychiatric variables were anger [55] and BHI-2 chronic maladjustment scale scores [55]. The only pain variable found to be predictive was pain range scores [55]. Discussion A number of observations can be derived from the results in Table 1, which divides the available studies by SI, SA,

and SC. Firstly, the association between SI and pain was consistent (A) in “by type of population” and for greater prevalence percentages in CPPs vs controls (Table 1). There was also a consistently (A) greater prevalence of SI within APPs vs controls (Table 1). Secondly, for SA, the association between SA and pain was also consistent (A) by “type of population.” For SA prevalence in CPPs vs controls, there were not enough studies for a consistency rating. Adding three studies that had previously been reviewed, however, gave an A consistency rating here. In APPs, for SA, there were not enough studies for a consistency rating. Thirdly, for SC, the association between SC and pain was also consistent (A) in “by type of population.” However, for SC for CPPs vs controls, there were not enough studies for a consistency rating. Adding three studies that had previously been reviewed gave four studies, all of which demonstrated a greater prevalence of SC in CPPs vs controls for an A consistency rating. Overall, combining the research reviewed here plus, if necessary, previously reviewed literature, there is strong consistent evidence for an association between SI, SA, and SC and pain in different types of populations and CPPs. Lack of studies comparing CPPs with controls for various forms of suicidality was previously identified as a problem with this literature [22]. As demonstrated here, there are now more of these types of studies that are consistent in their results. However, these studies are still rare. There is an obvious reason for lack of studies in reference to SA and SC where CPPs are compared with non-pain controls. SA and SC are much rarer events than SI in both the general population and in CPPs, while SC is a much rarer event than SA. As such, studies for SA and SC are much more difficult to do than for SI. As most patients who proceed to SA and SC first demonstrate SI, the results here are nevertheless important for the association of suicidality and pain. However, risk factors that predict SI may not necessarily predict SA and/or SC. As such, more studies on the association of pain and SA and SC are needed. It is to be noted that the data in Table 1 for by type of population was subdivided into studies that were prospective and studies that were controlled for behavioral variables such as depression. This is because to really demonstrate an association between pain and suicidality, ideally one should do a prospective study to see if suicidality develops as a consequence of pain development controlling for various variables. Such a design controls for self-reporting errors, recall bias, and memory failure [22]. As pointed out by Tang and Crane [22], the studies available for their review did not control for psychiatric variables and were rarely prospective. In the new studies reviewed here for SI, SA, and SC by type of population, there were a significant number of studies that had controlled for behavioral issues. In each of these 1839

Fishbain et al. subgroups, an A consistency rating was generated. Thus, controlling for these variables that have a significant impact on suicidality, there is still an association between these types of suicidality and pain. In reference to prospective studies, there were not enough studies for SI and SA to reach a consistency rating, but enough studies for SC to do so. SC prospective studies were consistent in demonstrating that there is an association between SC and pain in by type of population. It is also to be noted that some of the studies for SI, SA, and SC by type of population controlled for disability, social, and demographic factors. Failure to control for these variables has previously been pointed out as a major problem with this literature [22]. As noted here, this new literature has addressed this potential confounder. Besides the large number of studies added to this literature since the last review, there is another positive aspect to this literature not discussed above. The studies for SI, SA, and SC by type of population addressed a number of different population groups, subgroups, and countries: US adults, older home meal recipients, patients with major depressive disorder from Germany, adolescents, terminally ill patients, cancer patients, Canadian adults, US veterans, Korean adults, burn patients, medical students in Taiwan, Australian primary care patients, patients from emergency rooms, adults from Hong Kong, Scottish cancer patients, depressed geriatrics, survivors of childhood cancer, human immunodeficiency virus patients, suicidal attempters in India, internal medicine outpatients, World Health survey group (14 countries), Finnish children, suicides in India, Japanese adults, and veterans on opioids. These studies also addressed various forms of pain: headache, pain in general, abdominal pain, etc. The vast majority of these studies demonstrated an association between pain and suicidality. This indicates that the association between pain and suicidality relates to various subgroups, countries, and cultures and may apply to different forms of pain. Another interesting aspect to these new pain–suicidality studies are the reports on the association of suicidality and pain in APPs. If the association between suicidality and pain is true, then one should also be able to demonstrate such an association in APPs. The studies reviewed here indicate that such an association does exist for SI in APPs. This finding then indirectly supports the concept that there is an association between pain and forms of suicidality. This new literature has also added a host of predictor variables for SI, SA, and SC in CPPs, which are presented under the results. A number of general observations can be derived from this list. Firstly, a predictor for one type of suicidality, e.g., SI does not necessarily predict other types. Secondly, because of the difficulty in performing SC studies, few predictors are identified here. Thirdly, a number of pain and depression variables are similarly identified as per previous reviews [22]. Fourthly, smoking is identified as one of the new predictors for SI. This is important because smoking has been consistently identified as a variable 1840

associated with suicidality in psychiatric patients [53]. As such, this finding also translates to CPPs. Fifthly, disability has long been known to be a predictor of suicidality in psychiatric patients [84]. It appears that this variable is also a predictor within CPPs for SI [84,85]. Sixthly, an interesting new variable found to be predictive for SI in CPPs is that of burdensome perception [52,85,87]. This variable dovetails in with another variable found to be predictive for SI: treated unfairly by family [84]. Finally, the variables of sexual/ physical abuse have long been identified as being associated with suicidality in psychiatric patients [86]. Sexual/ physical abuse also often leads to posttraumatic stress disorder, which itself is associated with suicidality [90] and CP conditions [91]. As noted, sexual/physical abuse was found to be a predictor for SI [86]. The above studies from the psychiatric literature then indirectly support this finding. However, the psychiatric literature is inconsistent as different authors have defined sexual/physical abuse in different ways, probably leading to inconsistent results [92]. Lastly, the variables of male sex, older age, functional impairment, poor relationship with family, family history of mental disorders, aggression, depression, anxiety, borderline syndrome, and hallucinations have all previously been identified in the psychiatric literature as being associated with increased risk of suicide [21] and were identified as predictor variables in the reviewed studies. Thus, the previous psychiatric literature indirectly supports the results of these studies. What are the potential confounders to the results of this review? First, there is significant difficulty in making a distinction between true SA and a suicide gesture or nonsuicidal self-injury, e.g., self-cutting [93]. It is unclear if the studies included in this review under SA were able to make this distinction or simply classified non-suicidal selfinjury as SA. Second, many CPPs are treated with drugs for their pain, e.g., anticonvulsants. Suicidality has been reported as a consequence of antiepileptic drugs [94] and other drugs [95]. None of the reviewed studies controlled for this issue. Thus, this could have been a potential confounder to some of the CPP studies. Third, in reference to SC in CPPs, the one new study [58] related to fibromyalgia and did not deal with men but only women. Men have a suicide rate twice that of women. Thus, this study may have limited applicability in answering the SC and CP association question. Fourth, this was a structured narrative review, which used a “ballot box” or “vote counting” approach to count the studies that did/did not support the association of pain and suicidality. It then utilized the AHRQ guidelines to rate the consistency of the studies in supporting the pain–depression association. Although this approach raises this review above that of a simple narrative review, it does not meet criteria for an evidence-based systemic review and is not being presented as such. This is because any and all studies addressing this association were included without regard to the quality of the studies, which was not rated. As such, this issue is a significant potential confounder to the results of this review. Finally, the first author abstracted the data (as to whether the study demonstrated/did not demonstrate the association of pain and suicidality), which

The Association of Pain and Suicidality was not checked or verified by an independent reviewer. Although the results were checked twice, there could have been errors in the abstraction process leading to potential confounding. The results of this review also point to some new directions for research in this area. First, as pointed out, more prospective studies for SA and SC are needed for CPPs, and these studies should control for psychiatric and behavioral variables. Second, as noted for predictor variables, there were no studies that appeared to actually look at whether psychiatric diagnoses are predictive for SI, SA, and SC in CPPs. It is well known that psychiatric diagnoses such as major depression, alcohol use disorders, substance use disorders, etc., are associated with increased risk of suicidality [21]. As such, future studies need to actually control for individual diagnoses. Third, although some studies reviewed here had looked at pain subgroups such as headache pain, abdominal pain, etc., no studies had looked at the neuropathic pain subgroup. This subgroup is important as there is some recent evidence that it may be commonly found in CPPs [96]. Its relationship to suicidality is currently unclear. Fourth, physical diagnoses, such as chronic obstructive pulmonary disease, lupus, malignancy, chronic renal failure, etc., have also been identified as being factors associated with suicidality. Future studies in this area should also attempt to control for these variables. Finally, to take this research to a new level, a neurobiological mechanism for pain and depression needs to be clarified. Currently, it is believed that the neurological circuiting for emotions and pain in the nervous system are closely associated [97], and this may be the reason for the association of pain and depression, i.e., overstimulation of one circuit affects the other. Recently, it has also been demonstrated with functional magnetic resonance imaging in major depression that there are regions of the brain with abnormally enhanced activation at baseline. These regions are responsive to painful stimuli, and this responsiveness can be decreased by the antidepressant duloxetine [98]. These findings would lead one to design a functional magnetic resonance imaging study comparing the responsiveness of these regions to painful stimuli in three groups: CPPs without depression; CPPs with depression, but without suicidality; and CPPs with depression and SI or SA. Such a design could potentially lead to better understanding of the underlying neurologic mechanism for the association of pain and suicidality and perhaps a model. What is the target audience for this review? The target audiences for this review are pain physicians, family practice physicians, psychiatric physicians, and any and all clinicians that deal with pain patients. Each of these groups has their own unique problems in dealing with pain patients with this association, which relates to the nature of their specialty. Pain physicians focus on pain and routinely fail to address or ask about depression or suicidality. The most common presentation to family practice physicians is pain. As such, and similar to pain physicians, this group focuses on pain and fails to evaluate the pain

patient for depression and suicidality. Psychiatric physicians in turn focus on psychiatric pathology and thereby identify depression in their patients, but rarely inquire about pain status and thereby may not relate any suicidality they identify to pain [99]. This last observation also applies to other behavior clinicians such as psychologists. Other clinicians in contact with pain patients, such as physical therapists, focus on pain and activation and rarely inquire about depression and suicidality. Overall, the problem is one of division of medical care according to specialty training with the evaluation approach geared to that specialty. This often results in failure to identify the pain suicidality association. Finally, when should clinicians worry and what should they do? There are two possible approaches to this problem. One approach is to routinely measure depression and suicidality in any CPP with such tools as the Beck Depression Inventory at every visit. Here, if any suicidality is recorded, then that clinician could immediately refer the CPP for psychiatric/behavioral evaluation for treatment recommendations. The second approach would be to routinely monitor pain and depression with such tools as the Brief Pain Inventory at every CPP visit. High scores on pain or high scores on depression on the rating scales in this tool should alert the clinician to inquire about suicidality or refer the CPP for psychiatric/behavioral evaluation. Direct inquiries about suicidality can be performed by asking, “Because of the pain, have you felt that life is not worth living (passive suicidality)”? A positive response should result in referral for a psychiatric/ behavioral evaluation. Conclusions Since the last review on the association of pain and suicidality, there have been 58 studies added to this literature. Within the limits of this narrative review, overall, these studies plus, when necessary, previous studies are consistent utilizing AHRQ criteria in indicating that there is an association between SI, SA, and SC and pain. References 1 Chaturvedi SK. Psychalgic depressive disorder: A descriptive comparative study. Acta Psychaitr Scand 1989;79:98–102. 2 Breitbart W. Suicide in cancer patients. Oncology 1987;1:49–53. 3 Breitbart W. Cancer pain and suicide. In: Foley K, Bonica JJ, Ventafridda V, eds. Advances in Pain Research and Therapy: Second International Congress on Cancer Pain, Vol. 16. New York: Raven Press; 1990:399–412. 4 Stensman R, Sundqvist-Stensman U. Physical disease and disability among 416 suicide cases in Sweden. Scand J Soc Med 1988;16:149– 53. 1841

Fishbain et al. 5 Salyavathi K, Murti Rao DLN. Suicide in Bangalore. Transactions of AIIMH, Bangalore 1961;2:1. 6 Venkoba RA. Suicide attempters in Madurai. J Indian Med Assoc 1971;57:278–84. 7 Venkoba RA. Physical illness, pain and suicidal behavior. Crisis 1990;11:48–56. 8 Viskum K. Ulcers and attempted suicide, and suicide. Acta Psychiatr Scand 1975;51:221–7. 9 Fishbain DA, Goldberg M, Rosomoff RS, Rosomoff H. Case report: Completed suicide in chronic pain. Clin J Pain 1991;7:29–36. 10 Hitchock LS, Ferrell BR, McCaffery M. The experience of chronic non-malignant pain. J Pain Symptom Manage 1994;9:312–8. 11 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 Manage 1994;9:175–85. 12 Breitbart W, Passik SD, Eller K, et al. Suicidal Ideation in AIDS. The Roles of Pain and Mood (Abstract 145). Washington, DC: American Psychiatric Association Annual Meeting; 1992. 13 Stenager EN, Stenager E, Jensen K. Attempted suicide, depression and physical diseases: A 1-year follow-up study. Psychother Psychosom 1994;61: 65–73. 14 Breslau N, Davis GC, Andreski P. Migraine, psychiatric disorders, and suicide attempts: An epidemiologic study of young adults. Psychiatry Res 1991; 37:11–23. 15 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;76:137–44. 16 Covington E, Colburn K, Gonsales L Chronic pain and suicide: A review of six cases. Seventh World Congress on Pain 1993 Paris, France, A442, p 164. 1993. 17 Pentinen J. Back pain and risk of suicide among Finnish farmers. Am J Public Health 1995;85: 1452–3.

20 Fishbain DA. The association of chronic pain and suicide. Semin Clin Neuropsychiatry 1999;4(3): 221–7. 21 American Psychiatric Association. Practice Guideline for the Assessment and Treatment of Patients with Suicidal Behaviors. Arlington, VA: American Psychiatric Association; 2003:1–117. 22 Tang NK, Crane C. Suicidality in chronic pain: A review of the prevalence, risk factors and psychological links. Psychol Med 2006;36:575–86. 23 Treharne G, Lyons AC, Kitas GD. Suicidal ideation in patients with rheumatoid arthritis. Research may help identify patients at high risk [comment]. Brit Med J 2000;321:18. 24 Fisher BJ, Haythornthwaite JA, Heinbert LJ, Clark M, Reed J. Suicidal intent in patients with chronic pain. Pain 2001;89:199–206. 25 Smith MT, Edwards RR, Robinson RC, Dworkin RH. Suicidal ideation, plans, and attempts in chronic pain patients: Factors associated with risk. Pain 2004b;111:201–8. 26 Smith MT, Perlis ML, Haythornthwaite JA. Suicidal ideation in outpatients with chronic musculoskeletal pain: an exploratory study of the role of sleep onset insomnia and pain intensity. Clin J Pain 2004a; 20:111–8. 27 Timonen M, Viilo K, Hakko H, et al. Suicides in persons suffering from rheumatoid arthritis. Rheumatol 2003;42:287–91. 28 Macfarlane GJ, McBeth J, Silman AJ. Widespread body pain and mortality: prospective population based study. Brit Med J 2001;323:1–5. 29 Spiegel B, Schoenfelds P, Naliboff B. Systematic review: The prevalence of suicidal behavior in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther 2007;26: 183–93. 30 Agency for Healthcare Research and Quality. Systems to rate the strength of scientific evidence. Evidence Report/Technology Assessment #47. AHRQ Publication no. 02-EO16, 2002.

18 Thorn H. “Central” pain can raise suicide risk. Clin Psychiatric News 1994;July:11.

31 Britton PC, Ilgen MA, Valenstein M, et al. Differences between veteran suicides with and without psychiatric symptoms. Am J Pub Health 2012;102(suppl 1):S125–30.

19 Breitbart W, Rosenfeld BD, Passik SD. Interest in physician-assisted suicide among ambulatory HIV-infected patients. Am J Psychiatry 1996;153: 238–42.

32 Ilgen MA, Zivin K, Austin KL, et al. Severe pain predicts greater likelihood of subsequent suicide. Suicide & Life-Threatening Behavior 2010;40(6):597– 608.

1842

The Association of Pain and Suicidality 33 Ilgen MA, Kleinberg F, Ignacio RV, et al. Noncancer pain conditions and risk of suicide. JAMA Psychiatry 2013;May 22:1–6. 34 Manoranjitham SD, Rajkumar AP, Thangadurai P, et al. Risk factors for suicide in rural south India. Brit J of Psychiatry 2010;196(1):26–30. 35 Kikuchi N, Ohmori-Matsuda K, Shimazu T, et al. Pain and risk of completed suicide in Japanese men: A population-based cohort study in Japan (Ohsaki Cohort Study). J Pain Symp Manage 2009;37(3): 316–24. 36 Fishbain DA, Bruns D, Disorbio JM, Lewis JE. Risk for five forms of suicidality in acute pain patients and chronic pain patients vs pain-free community controls. Pain Med 2009;10(6):1095–105. 37 Magruder KM, Yeager D, Brawman-Mintzer O. The role of pain, functioning, and mental health in suicidality among veterans affairs primary care patients. Am J Pub Health 2012;102(S1):S118– 24. 38 Ratcliffe GE, Enns MW, Belik SL, Sareen J. Chronic pain conditions and suicidal ideation and suicide attempts; an epidemiologic perspective. Clin J Pain 2008;24(3):204–10. 39 Gensichen J, Teising A, Konig J, et al. Predictors of suicidal ideation in depressive primary care patients. J Affective Disorders 2010;125(1–3):124–7. 40 Sirey J, Bruce ML, Carpenter M, et al. Depressive symptoms and suicidal ideation among older adults receiving home delivered meals. Int J Geriatr Psychiatry 2008;23:1306–11. 41 Chochinov HM, Wilson KG, Enns M, et al. Desire for death in the terminally ill. Am J Psychiatry 1995;152:1185–91. 42 Mystakidou K, Parpa E, Katsourda E, Galanos A, Flahos L. Pain and desire for hastened death in terminally ill cancer patients. Cancer Nurs 2005; 28(4):318–24.

United States. Gen Hosp Psychiatry 2008;30(6): 521–7. 46 Van Tilburg MAL, Spence NJ, Whitehead WE, Bangdiwala S, Goldston DB. Chronic pain in adolescents is associated with suicidal thoughts and behaviors. J Pain 2011;12(10):1032–9. 47 Li LW, Conwell Y. Pain and self-injury ideation in elderly men and women receiving home care. J Am Geriatr Soc 2010;58(11):2160–5. 48 Breslau N, Davis GC, Andreski P. Migraine, psychiatric disorders, and suicide attempts: An epidemiologic study of young adults. Psychiatry Res 1991;37:11–23. 49 Bahk WM, Park S, Jon DI, et al. Relationship between painful physical symptoms and severity of depressive symptomatology and suicidality. Psychiatry Res 2011;189(3):357–61. 50 Theodoulou M, Harriss L, Hawton K, Bass C. Pain and deliberate self-harm an important association. J Psychosom Res 2005;58:317–20. 51 Calandre EJP, Vilchez JS, Molina-Barea R, et al. Suicide attempts and risk of suicide in patients with fibromyalgia: A survey in Spain. Rheumatol 2011; 50(10):1889–93. 52 Kowal J, Wilson KG, McWilliams LA, Peloquin K, Duong D. Self-perceived burden in chronic pain: Relevance, prevalence, and predictors. Pain 2012; 153(8):1735–41. 53 Fishbain DA, Lewis JE, Gao J, Cold C, Rosomoff RS. Are chronic low back pain patients who smoke at greater risk for suicide ideation? Pain Med 2009; 10(2):340–6. 54 Fishbain DA, Bruns D, Lewis JE, et al. Predictors of homicide-suicide affirmation in acute and chronic pain patients. Pain Med 2011;12:127–37. 55 Fishbain DA, Lewis JE, Bruns D, et al. Patient predictor variables for six forms of suicidality. Eur J Pain 2011;16:706–17.

43 Edwards RR, Magyar-Russell G, Thombs B, et al. Acute pain at discharge from hospitalization is a prospective predictor of long-term suicidal ideation after burn injury. Arch Phys Med Rehabil 2007;88(12 suppl 2):S36–42.

56 Juurlink DN, Herrmann N, Szalai JP, Kopp A, Redelmeier DA. Medical illness and the risk of suicide in the elderly. Arch Intern Med 2004;164:1179– 84.

44 Braden JB, Sullivan MD. Suicidal thoughts and behavior among adults with self-reported pain conditions in the national comorbidity survey replication. J Pain 2008;9(12):1106–15.

57 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 Manage 1994;9(3):175–85.

45 Ilgen MA, Zivin K, McCammon RJ, Valenstein M. Pain and suicidal thoughts, plans and attempts in the

58 Wolfe F, Hassett A, Walitt B, Michaud K. Mortality in primary fibromyalgia: A study of 8,186 patients over 1843

Fishbain et al. thirty-five years. Arthritis Care Res 2011;63(1):94– 101. 59 Dreyer L, Kendall S, Danneskiold-Samsoe B, Bartels EM, Bliddal H. Mortality in a cohort of Danish patients with fibromyalgia: Increased frequency of suicide. Arthritis Rheum 2010;62(10):3101–8. 60 Hyungjin MK, Smith EG, Ganoczy D, et al. Predictors of suicide in patient charts among patients with depression in the Veterans Health Administration Health System: Importance of prescription drug and alcohol abuse. J Clin Psychiatry 2012;73(10):e1269– 75.

70 Amir M, Neumann L, Bor O, et al. Coping styles, anger, social support, and suicide risk of women with fibromyalgia syndrome. J Musculoskeletal Pain 2000;8(3):7–20. 71 Luntamio T, Sourander A, Gyllenberg D, et al. Do headaches and abdominal pain in childhood predict suicide and severe suicide attempts? Finnish Nationwide 1981 Birth Cohort Study. Child Psych Hum Dev 2014;45:110–8. 72 Almeida OP, Draper B, Snodon J, et al. Factors associated with suicidal thoughts in a large community study of older adults. Br J Psychiatry 2012; 201(6):466–72.

61 Saffier K, Colombo C, Brown D, Mundt MP, Fleming MF. Addiction severity index in a chronic pain sample receiving opioid therapy. J Substance Abuse Treatment 2007;33:303–11.

73 Breslau N, Schultz L, Lipton R, Peterson E, Welch KM. Migraine headaches and suicide attempt. Headache 2012;52(5):723–31.

62 Woolley SBG, Fredman L, Goethe JW, Lincoln AK, Heeren T. Headache complaints and the risk of suicidal thoughts or behaviors. J Nerv Ment Dis 2008;196:822–8.

74 Foldes-Busque G, Fleet R, Portras J, et al. Suicidality and panic in emergency department patients with unexplained pain. General Hosp Psych 2012;34: 178–84.

63 Scott KM, Hwang I, Chiu WT, et al. Chronic physical conditions and their association with first onset of suicidal behavior in the world mental health surveys. Psychosom Med 2010;72(7):712–9.

75 Tektonidou MG, Dasgupta A, Ward MM. Suicidal ideation among adults with arthritis: prevalence and subgroups at highest risk. Data from the 2007–2008 National Health and Nutrition Examination Survey. Arthritis Care Res 2011;63(9):1322–33.

64 Hepner KA, Watkins KE, Elliott MN, et al. Suicidal ideation among patients with bladder pain syndrome/interstitial cystitis. Urology 2012;80(2): 280–5. 65 Park S, Cho MJ, Seong S, et al. Psychiatric morbidities, sleep disturbances, suicidality, and quality-of-life in a community population with medically unexplained pain in Korea. Psychiatry Res 2012;198(3): 509–15. 66 Halvorsen JA, Dalgard F, Thoresen M, Bjertness E, Lien L. Itch and pain in adolescents are associated with suicidal ideation: A population-based crosssectional study. Acta Derm Venereol 2012;92(5): 543–6. 67 Fan AP, Kosik RO, Mandell GA, et al. Suicidal ideation in medical students: Who is at risk? Ann Acad Med Singapore 2012;41(9):377–82. 68 Madadi P, Hildebrandt D, Lauwers AE, Koren G. Characteristics of opioid-users whose death was related to opioid toxicity: A population-based study in Ontario, Canada. PLoS ONE 2013;8(4):e60 600. doi: 10.1371/journal.pone.0060600. Epub 2013 Apr 5. 69 Sansone RA, Watts DA, Wiederman MW. Pain, pain catastrophizing, and history of intentional overdoses and attempted suicide. Pain Pract 2013;13:239– 45. 1844

76 Chan WS, Law CK, Liu KY, et al. Suicidality in Chinese adolescents in Hong Kong: The role of family and cultural influences. Soc Psychiatry Psychiatr Epidemiol 2009;44(4):278–84. 77 Walker J, Waters RA, Murry G, et al. Better off dead: Suicidal thoughts in cancer patients. J Clin Oncol 2008;26(29):4725–30. 78 Jeeis TW, Dunn LB, Kim DS, et al. Chronic pain and depression among geriatric psychiatry inpatients. Int J Geriatr Psychiatry 2008;23(6):637–42. 79 Recklitis CJ, Lockwood RA, Rothwell MA, Diller LR. Suicidal ideation and attempts in adult survivors of childhood cancer. J Clin Oncol 2006;24(24):3852–7. 80 Thompson KL, Kane TF, Cook JM, et al. Suicidal ideation in veterans receiving treatment for opiate dependence. J Psychoactive Drugs 2006;38(2):149– 56. 81 Srivastava MK, Sahoo RN, Ghotekar LH, et al. Risk factors associated with attempted suicide: A case control study. Indian J Psychiatry 2004;46(1):33–8. 82 Dafoe ME, Stewart KE. Pain and psychiatric disorders contribute independently to suicidal ideation in HIV-positive persons. Arch Suicide Res 2004;8(3): 215–26.

The Association of Pain and Suicidality 83 Akechi T, Okamura H, Nishiwaki Y, Uchitomi Y. Predictive factors for suicidal ideation in patients with unresectable lung carcinoma. Cancer 2003;97(12): 3127–8. 84 Fishbain DA, Bruns D, Meyer LJ, et al. Exploration of the relationship between disability perception, preference for death over disability, and suicidality in patients with acute and chronic pain. Pain Medicine 2012;13:552–61. 85 Wilson KG, Kowal J, Henderson PR, McWilliams LA, Peloquin K. Chronic pain and the interpersonal theory of suicide. Rehabil Psychol 2013;58(1):111–5. 86 Cheatle M, Wasser T, Olugbodi A, Foster C. The prevalence and mediators of suicidal ideation in patients with chronic non-cancer pain. J Pain 2013;14(4):S24. A194,+9999999999999 + 9 +++9999999 + 99. 87 Kanzler KE, Bryan CJ, McGeary DD, Morrow CE. Suicidal ideation and perceived burdensomeness in patients with chronic pain. Pain Pract 2012;12(8): 602–9. 88 Edwards RR, Smith MT, Kudel I, Haythornthwaite J. Pain-related catastrophizing as a risk factor for suicidal ideation in chronic pain. Pain 2006;126:272–9. 89 Breslau N. Migraine, suicidal ideation, and suicide attempts. Neurology 1992;42:392–5. 90 Sareen J, Houlahan T, Cox BJ, Asmundson GJG. Anxiety disorders associated with suicidal ideation and suicide attempts in the national comorbidity survey. J Nerv Ment Dis 2005;193(7):450–4. 91 Sareen J, Cox BJ, Stein MB, et al. Physical and mental comorbidity, disability, and suicidal behavior associated with posttraumatic stress disorder in a large community sample. Psychosom Med 2007;69(3):242–8. 92 Fishbain DA, et al. Exploration of affirmation of childhood molestation (sexual abuse) in chronic pain

patients with pain and community non-patients without pain. Pain Pract 2013;13:145–52. 93 Nock MK, Kessler RC. Prevalence and risk factors for suicide attempts vs suicide gestures: Analysis of the nation al comorbidity survey. J Abnorm Psychol 2006;115:6616–23. 94 Pereira A, Gitlin MJ, Gross RA, Posner K, Dworkin RH. Suicidality associated with antiepileptic drugs: Implications for the treatment of neuropathic pain and fibromyalgia. Pain 2013;154(3):345–9. 95 Pinho de Oliveira Ribeiro N, Rafael de Mellor Schier A, Ornelas AC, et al. Anxiety, depression, and suicidal ideation in patients with rheumatoid arthritis in use of methotrexate, hydroxychloroquine, leflunomide and biological drugs. Compr Psychiatry 2013;S0010-440X(13):00120-X, pii. doi: 10.1016/ j.comppsych.2013.05.010. 96 Fishbain DA, Cole B, Lewis JE, Gao J. What is the evidence that neuropathic pain is present in chronic low back pain and soft tissue syndromes? An evidence-based structured review. Pain Med 2014; 14:4–15. 97 Giesecke T, Gracely RH, Williams DA, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum 2005;52(5):1577–84. 98 Lopez-Sola M, Pujol J, Hernandez-Ribas R, et al. Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder. Neuropsychopharmacology 2010;35(11):2305– 17. 99 Rijavec N, Grubic VN. Depression and pain: Often together but still a clinical challenge—A review. Psychiatr Danub 2012;24(4):346–52. 100 Calandre EP, Navajas-Rojas A, Ballesteros J, et al. Suicidal ideation in patients with fibromyalgia: A cross-sectional study. Pain Pract 2014;14:232– 40.

1845

Fishbain et al. Appendix

Table A1

Suicide ideation and pain by type of population

Type of Population and Study Type 1. US community-dwelling adults prospective over 2 years (N = 6,832) [62] (Type 3) (prospective) (controlled) 2. Older recipients, county home meal program (N = 403) [40] (Type 4) 3. Patients with MDD ages 18–80 in primary care practices in Germany (N = 626) [39] (Type 4) (controlled) 4. Elderly participants in home care program, average age 77.5 (N = 16,700) [47] (Type 4) 5. US adolescents grades 7–12, two interviews, 1 year apart (N = 9,970) [46] (Type 3) (prospective) (controlled) 6. US civilian adults aged 18 or older (N = 5,692) [44] (Type 4) (controlled) 7. Terminally ill medical inpatient patients (N = 200) [41] (Type 4) 8. Canadians from all 10 provinces aged 15 and above living in private dwellings (N = 36,984) [38] (Type 4) (controlled) 9. Veterans in treatment in primary care (N = 884); those with suicidal ideation compared with those without [37] (Type 3) (controlled) 10. Terminally ill cancer patients in Greece (N = 120) [42] (Type 4) 11. English-speaking US households (N = 5,692) [45] (Type 4) (controlled) 12. Survivors of major burns discharged from rehabilitation units (N = 128) (prospective) [43] (Type 3) (controlled) 13. Korean Household Catchment Area Study of patients with medically unexplained pain (N = 6,510) [65] (Type 4) 14. Male and female adolescents with itch and pain (N = 4,744) [66] (Type 4) 15. Medical students in Taiwan [67] (Type 4) 16. Adults aged 60 to101 from Australian primary care practices (N = 21,290) [72] (Type 4) 17. Emergency department patients with unexplained chest pain (N = 572) [74] (Type 4) 18. Community sample of adolescents aged 15–19 in Hong Kong (N = 511) [76] (Type 4) 19. Consecutive patients from outpatient cancer clinic in Scotland (N = 2,924) [77] (Type 4) 20. Depressed geriatric patients in a psychiatry unit (N = 148) [78] (Type 4) 21. Adult survivors of childhood cancer (N = 226) [79] (controlled) (Type 4) 22. Veterans receiving treatment for opioid dependence (N = 101) [80] (Type 4) 23. HIV-positive individuals (N = 75) [82] (Type 4) (controlled) 24. Patients with undetectable non-small cell lung cancer (N = 89) at 6 months after diagnosis [83] (Type 4) 25. US adults with arthritis age >40 in 2007–2008 (N = 1,545) [75] (Type 3)

Pain Associated with SI? Yes. Controlling for demographics, psychiatric diagnoses, and interaction of anxiety and depression, it was demonstrated that severe headache was associated with the development of SI. Yes. In men only, pain was strongly associated with SI and greater depression severity. Pain predicted SI. Yes. Physical pain in multivariate analysis was significantly associated with SI. Yes. Risk of SI increased in men only with pain severity. Yes. Controlling for depressive symptoms, headaches and muscle aches were associated with SI development. Yes. Controlling for demographics and medical and mental covariates, any pain condition remained significantly associated with SI. Yes. SI (desire for death) correlated with ratings for pain. Yes. Controlling for sociodemographic variables and DSM Axis I disorders, presence of one or more pain conditions was associated with SI. No. Controlling for sociodemographics and functioning and psychiatric diagnoses, no pain variable remained significant. Yes. Current pain and average pain predicted SI (desire for death). Yes. Controlling for demographics, chronic health conditions, and psychiatric disorders, chronic head pain and pain summary score were related to SI. Yes. Pain severity was the sole predictor of SI at follow-up controlling for mental health. Yes. Patients with medically unexplained pain symptoms reported more SI than those without. Yes. SI prevalence was 8.4% in those without itch and 21.1% in those with severe itch. Significant association in a multivariate model between itch and SI and between pain and SI. Yes. SI was significantly higher in those students with headache or noninflammatory joint pain. Yes. Pain was independently associated with SI. Yes. Fifteen percent report current SI (95% confidence interval 12–18%). Yes. Chronic pain was a risk factor for SI. Yes. Substantial pain was associated with current SI. Yes. In multivariate analysis, patients with chronic pain were more likely to report SI. Yes. By hierarchical regression analysis, pain was significantly associated with SI after adjusting for treatment and depression variables. Yes. Twenty-four reported SI. Severe chronic pain was associated with SI. Yes. By sequential logistic regression analysis, pain severity independently predicted SI after controlling for psychiatric diagnosis. Yes. Multivariate analysis indicated that pain at baseline was a significant predictive factor for SI. Yes. SI correlated with presence of pain.

DSM = Diagnostic and Statistical Manual of Mental Disorders; HIV = human immunodeficiency virus; MDD = major depressive disorder; SI = suicide ideation.

1846

The Association of Pain and Suicidality

Table A2

Suicide attempts and pain by type of population

Type of Population and Study Type

Pain Associated with SA?

1. Consecutive suicide attempt admits (N = 1,665) [50] (Type 4)

Unknown. Four percent had pain as a contributing factor. (This study is only presented for completeness and is not used in the calculations as it did not address the association.) No. After controlling for depression, headaches and muscle aches were not associated with SA. Yes. Adjusting for demographics and Axis I DSM4 mental disorder, presence of one or more pain conditions was associated with SA in the last 12 months. Yes. Controlling for demographics and medical and mental covariates, presence of chronic pain was significantly associated with lifetime SA. Yes. In multivariate models, adjusting for concurrent psychiatric disorders and chronic medical conditions (last 12 months), SA was associated with head pain and pain summary scores. Other non-arthritic pain was also associated with SA. Yes. After controlling for demographic, socioeconomic, psychosocial, and mental disorders, arthritis, chronic headache, and other chronic pain were associated with SA. Yes. There was a statistically significant relationship between all pain variables (pain today and over past month, and past year) and history of intentional overdose. Yes. Thirty-nine individuals with SA. In boys, abdominal pain predicted future SA/SC.

2. Adolescents grades 7–12 (N = 9,970) [46] (Type 4) (controlled) 3. Age 15 and above living in all 10 provinces in Canada in private dwellings (N = 28,477) [38] (Type 4) (controlled) 4. US civilian adults 18 or older (N = 5,962) [44] (Type 4) (controlled) 5. US households, English speaking (N = 5,692) [45] (Type 4) (controlled)

6. World Health Survey, 14-country sample (N = 37,915) [63] (Type 4) (controlled) 7. Internal medicine outpatients (consecutive) N = 239 [69] (Type 4) 8. *Prospective study in Finland of children (mid-childhood) followed to age 24 for SA requiring hospitalization (N = 6,017) [71] (Type 3) (prospective) 9. Consecutive suicide attempts (N = 137) in Jawaharlal Hospital India compared with matched controls (N = 137) [81] (Type 3) (controlled)

Yes. Idiopathic pain was associated with increased risk of SA.

*This study did not separate SA from SC but analyzed the data together, calling it severe suicidality. DSM = Diagnostic and Statistical Manual of Mental Disorders; SA = suicide attempt; SC = suicide completion.

Table A3

Suicide completions and pain by type of population

Type of Population and Study Type

Pain Associated with Suicide Completions?

All suicide completions, two geographical areas, Veterans Health Administration system over 7-year period. (N = 381) [31] (Type 4)

Yes. Sixty-five point five percent had psychiatric symptoms, and this group was more likely to have pain compared with a group without psychiatric symptoms. Yes. Controlling for demographic and psychiatric characteristics, veterans with severe pain were more likely to die by suicide completion vs those with none, mild, or moderate pain. Yes. Chronic pain heightened risk for suicide completion.

Of large veteran population (N = 260,254) [32] (Type 4) (controlled)

Consecutive suicides in India matched to living controls for age, gender, neighborhood (N = 100) [34] (Type 3) Of large veteran population (4,863, 086) [33] (Type 4) (controlled)

Ontario residents 66 years or older who completed suicide between 1992 and 2000 (N = 1,354) compared with living matched controls [56] (Type 3) (controlled) Randomly selected veterans treated for depression who completed suicide between 2009–2004 (N = 324) were matched against live controls (N = 312) being treated for depression on date of suicide [60] (Type 3) (controlled) Of 26,481 Japanese men followed for 6 years for 131,027 person years, 64 completed suicide [35] (Type 3) (prospective) (controlled) *Prospective study in Finland of children (mid-childhood) followed to age 24 for SC (N = 6017) [71] (Type 3) (prospective) Deaths in patients on opioids for various reasons such as pain and addiction in Ontario between 2006 and 2008 (N = 1,359) [68] (Type 4)

Yes. After controlling for psychiatric conditions, a significant association was found for completed suicides and back pain, migraine, and psychogenic pain. Yes. Moderate pain and severe pain were associated with suicide completion. No. Chronic or acute pain was not associated with suicide completion.

Yes. Controlling for health, stress, sleep, physical activity, and chronic disease, a positive association between pain and suicide was demonstrated. Yes. SC occurred in 18 patients. There was an association between abdominal pain in boys and SC/SA. Yes. Suicides were significantly associated with chronic pain.

*This study did not separate SA from SC but analyzed the data for both groups together, calling it severe suicidality. SA = suicide attempt; SC = suicide completion.

1847

Fishbain et al.

Table A4 controls

Reported prevalence percentages of SI in CPPs and reported prevalence of SI in CCPs vs

Type of Ideation and Study Type

CPPs

Controls

1. CPPs in rehabilitation with homicide-suicide [54] (Type 3) *CPPs in pain rehab program with SI [85] (Type 4) CPPs in pain rehab program with preference for death over disability (passive SI) [84] (Type 3) 2. CPPs in a behavioral pain program with SI [86] (Type 4) *CPPs receiving opioid therapy with serious thoughts of suicide [61] (Type 4) *CPPs in a behavioral pain program answering item 9 Beck Depression Scale [87] (Type 4) 3. CPPs in rehabilitation with various SI: suicide plan 4. Wanting to die (passive) 5. Because of pain (passive) 6. Other SI 7. Wanting to die because life is hard (passive suicidality) [55] (Type 3) *CPPs treated in a pain program answering items 9 and 39 of the Brief Symptom Inventory (active and passive ideation) [88] (Type 4) *SI past 2 weeks in women with interstitial cystitis pain [64] (Type 4) 8. Suicide risk comparisons between patients with fibromyalgia, rheumatoid arthritis, low back pain and healthy women [70] (Type 3) 9. US adults with arthritis age > 40 in 2007–2008 [75] (Type 3)

(of N = 341) 4.40% (of N = 303) 40.9% (of N = 341) 18.5%

(of N = 1,329) 1.88%

*Spanish patients diagnosed with fibromyalgia reporting SI on BDI item 9 [100] (Type 3) 10. Korean patients with MDD compared for SI [49] (Type 3)

(of N = 129) 19.4%

(of N = 466) 20% (of N = 285) 31.9% men (of N = 623) 40.3% women (of N = 113) 15.0%

NA (of N = 1,478) 1.66% 18.06% 2.78% 3.16% 11.66%

(of N = 1,512) 22.1% passive SI, 24.5% active SI, 32% collective prevalence SI (of N = 1,019) 11.0% prevalence

(of N = 373) 48% reported SI (39.7% passive and 8.3% active) Patients with painful physical symptoms (PPS) (N = 125)

Yes NA No NA NA

(of N = 341) 7.92% 34.9% 14.08% 9.38% 24.93%

50 FMS 51 RA 50 LBP (of N = 1,545) 5.6% ± 0.8%

Significant Difference?

Yes Yes Yes Yes Yes NA

NA N = 50 (Healthy) (of N = 672) 2.4% ± 0.4%

No difference between groups Yes NA

Patients without PPS (N = 29)

Yes. Patients with PPS had significantly higher SI

*Studies that did not address the association of pain and suicidality, but only reported on the prevalence of suicidality in CPPs and are only presented here for completeness and are not utilized in the consistency calculations. BDI = Beck Depression Inventory; CPP = chronic pain patient; FMS = fibromyalgia syndrome; LBP = low back pain; MDD = major depressive disorder; NA = not applicable; RA = rheumatoid arthritis; SI = suicide ideation.

Table A5

Reported prevalence percentages of suicide attempts in CPPs vs controls

% in CPPs and Type of Study *SA prevalence in fibromyalgia patients (N = 180); 16.7% history of one to three attempts [51] (Type 4) *Of patients on opioids, lifetime prevalence of SA was 38% for males (of N = 285) and 23.8 % for females (of N = 623) [61] (Type 4) Of CPPs in rehabilitation, lifetime prevalence of SA was14.11% (of N = 326) [55] (Type 3) Patients with migraine (N = 496), non-migraine severe headache (N = 151), and controls with no history severe headache (N = 539) assessed in 1997 and 1999 and compared for incidence SA [73] (Type 3) (prospective) (controlled) Patients with migraine with aura (N = 59) and without aura (N = 69) compared with patients without migraine for SA [48] (Type 3)

Controls

Significant Difference? NA NA

6.32% (of N = 1,478) Yes Yes Adjusting for sex and psychiatric disorders, headache severity at baseline predicted SA in the entire sample. Yes. Patients with migraine had higher rates of SA than patients without migraine.

*Studies where only percentages of SA were reported and no comparisons with controls were made. These studies are only being reported for completeness and were not used in the consistency calculations. CPP = chronic pain patient; NA = not applicable; SA = suicide attempt.

1848

The Association of Pain and Suicidality

Table A6

Comparisons of SC in CPPs vs controls

Type of CPPs

Significant Difference?

Fibromyalgia patients seen between 1974 and 2009 (N = 8,186) compared with US general population for SC [58] (Type 3)

Yes. Standardized mortality odds ratio when compared with US general population was increased for SC.

CPP = chronic pain patient; SC = suicide completion.

Table A7

Prevalence of SI and SA in APPs who are in rehabilitation vs controls

Type of Ideation and Study Type

APPs (N = 326)

Controls (N = 1,478)

Significant Difference?

1. 2. 3. 4. 5. 6. 7.

7.06% 24.85% 6.13% 5.83% 19.01% 3.99% 14.11%

1.66% 18.06% 2.78% 3.16% 11.66% 1.88% 6.32%

Yes Yes Yes Yes Yes Yes Yes

Suicide plan [55] (Type 3) History of wanting to die [55] (Type 3) History of wanting to die because of pain [55] (Type 3) Recent frequent suicide ideation [55] (Type 3) Wanting to die because life is hard [55] (Type 3) For suicide-homicide [54] (Type 3) History of SA [55] (Type 3)

APP = acute pain patient; SA = suicide attempt; SI = suicide ideation.

Table A8

Levels of evidence as developed by the agency for health care research and quality [30]

Type of Evidence and Strength/Consistency of the Evidence Guidelines according to the AHRQ Type of evidence guidelines: • Meta-analysis of multiple well-designed controlled studies. • At least one well-designed experimental study. • Well-designed, quasi-experimental studies such as nonrandomized controlled, single group pre-post, cohorts, time series, or matched case-controlled studies. • Well-designed nonexperimental studies, e.g., comparative, correlational, descriptive, case control. • Case reports and clinical examples. Strength and consistency of evidence guidelines: • (A) There is evidence of type I or consistent findings from multiple studies of type II, III, or IV. • (B) There is evidence of type II, III, or IV, and findings are generally consistent. • (C) There is evidence of type II, III, or IV, but findings are inconsistent. • (D) There is little or no evidence, or there is type V evidence only. • (E) Panel consensus: practice recommended on the basis of opinion of experts. AHRQ = Agency for Healthcare Research and Quality.

1849

Copyright of Pain Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.