The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses.

The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Search Log in Primary site navigation Search Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice J Affect Disord . Author manuscript; available in PMC: 2026 Jun 2. Published in final edited form as: J Affect Disord. 2024 Oct 9;369:429–435. doi: 10.1016/j.jad.2024.10.028 The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses Erica A Abel a, b, c, 1 , Letitia E Travaglini d, 1 , Jennifer L Snow a, b , Joseph L Goulet a, b, e, * Author information Article notes Copyright and License information a Pain Research, Informatics, Multimorbidities and Education Center, VA Connecticut Healthcare System, West Haven, CT, United States b Yale Center for Medical Informatics, Yale School of Medicine, New Haven, CT, United States c Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States d VA Capital Healthcare Network (VISN 5) Mental Illness, Research, Education, and Clinical Center (MIRECC), Baltimore, MD, United States e Department of Emergency Medicine, Yale School of Medicine, New Haven, CT, United States 1 Co-first authors. * Corresponding author at: Pain Research, Informatics, Multimorbidities and Education Center, VA Connecticut Healthcare System, 950 Campbell Avenue, 11-ACSLG, West Haven, CT, United States. joseph.goulet@va.gov (J.L. Goulet). Issue date 2025 Jan 15. PMC Copyright notice PMCID: PMC13224097  NIHMSID: NIHMS2169845  PMID: 39389110 The publisher's version of this article is available at J Affect Disord Abstract Background: High suicide rates are documented among persons with bipolar disorder diagnoses and pain diagnoses, but few studies have examined the association of pain with suicide mortality in individuals with comorbid pain and bipolar disorders. This study assessed the association of pain screening and pain severity with suicide mortality among veterans with comorbid bipolar and musculoskeletal disorder (MSD) diagnoses. Methods: A retrospective cohort study was conducted on 168,021 patients within the Veterans Health Administration (VHA) who received an MSD diagnosis from 2000 to 2015 and had a bipolar disorder diagnosis. Pain severity, comorbidities, demographics, and suicide mortality were extracted from VHA databases. Poisson regression examined relative risk of suicide by the presence pain screening and pain severity ratings. Results: Pain was assessed in 72.73 % of veterans. Suicide risk was greater in those not assessed (0.98 % versus 0.77 % in assessed group). However, this result did not persist after adjusting for covariates (RR = 1.06). Among those assessed, higher suicide risk was associated with moderate (RR = 1.10), severe pain (RR = 1.06), and no pain (reference) relative to mild pain (RR = 0.99). Major depression, substance use disorders, and prescribed opioids and benzodiazepines increased risk. Limitations: Data were obtained from medical records; diagnoses were not confirmed via formal assessment, and no information was available on actual medication use or purpose. Over 25 % of the sample were missing pain severity ratings, which could have affected results. Conclusions: Suicide risk factors among persons with bipolar disorder are complex and multifactorial. Providers should prioritize suicide prevention efforts following new onset or worsening pain. Keywords: Veterans, Pain, Bipolar disorder, Suicide risk, Mental health, US Department of Veterans Affairs 1. Introduction Suicide is a major public health problem in the United States ( Kochanek et al., 2020 ). Within the Veterans Health Administration (VHA), 2 two groups disproportionately affected by suicide are Veterans with chronic pain ( Ilgen et al., 2013 ; Ilgen et al., 2010c ) and those diagnosed with bipolar disorder ( Schaffer et al., 2015b ), though no research to date has looked at suicide rates in Veterans with these comorbid conditions. Bipolar disorder diagnosis and pain conditions are highly comorbid ( Birgenheir et al., 2013 ), and medication use within both groups can elevate suicide risk ( O’Neill et al., 2019 ). A large proportion of the studies reporting on the association between bipolar disorder and pain begin with a cohort of patients diagnosed with bipolar disorder and then examine painful conditions or pain intensity in those individuals ( Birgenheir et al., 2013 ; Failde et al., 2013 ; Rahman et al., 2014 ; Stubbs et al., 2015 ; Subramaniam et al., 2013 ; Travaglini et al., 2020 ), rather than looking at rates of bipolar disorder within a pain cohort. 1.1. Pain and suicide Pain has been long recognized as a risk factor for suicide, with research finding rates up to 4-times greater in chronic pain populations ( Ashrafioun et al., 2018 ; Campbell et al., 2015 ; Ilgen et al., 2013 ; Ilgen et al., 2008 ; Lusk et al., 2015 ; Tang and Crane, 2006 ). Though not as heavily researched, acute pain experiences also hold their own suicide risk ( Fishbain et al., 2009 , 2012 ). A review by Tang and Crane (2006) found lifetime prevalence rates of suicide attempts between 5 % and 14 %, and lifetime ideation at approximately 20 % among individuals with chronic pain. Dying by suicide is more common among individuals experiencing severe (versus no, mild, or moderate) pain ( Ilgen et al., 2010a , 2010b , 2010c ). Other pain-related variables related to suicidality include having multiple pain complaints, increased pain-related disability, and perceived burdensomeness ( Park et al., 2019 ; Racine, 2018 ; Racine et al., 2014 ; Fishbain et al., 2012 , 2016 ). Co-occurring mental health (notably depression, anxiety, and posttraumatic stress disorder) and substance use disorders increase suicide risk ( Hassett et al., 2014 ; Racine, 2018 ), along with higher doses and longer-term use of opioids ( Dreyer et al., 2010 ; Saffier et al., 2007 ). Rates of suicide in chronic pain populations are often confounded by opioid overdose, with rates of suicidality high among individuals prescribed opioids ( Bohnert and Ilgen, 2019 ; Webster, 2017 ). Suicide risk is further elevated when individuals are prescribed – and potentially misusing – both opioids and benzodiazepines ( Schepis et al., 2019 ). Of note, presence of pain or pain severity are independently related to increased suicide risk even when controlling for other notable risk factors (e.g., age, race, homelessness; Campbell et al., 2015 ; Hassett et al., 2014 ; Racine et al., 2014 ). 1.2. Bipolar disorder and suicide Suicide rates are higher among individuals with bipolar disorder than any other mental health condition and are up to 20 times greater than the general population ( Ilgen et al., 2010a ; Miller and Black, 2020 ; Schaffer et al., 2015b ). Two reviews conducted by the International Society for Bipolar Disorders ( Schaffer et al., 2015a ; Schaffer et al., 2015c ) cited potential reasons for the increased suicide risk in this population, including: 1) genetic and neurobiological factors; 2) treatment factors such as duration of untreated illness, low medication adherence, and hospitalizations and post-discharge risk period; 3) clinical characteristics such as age and duration of illness and frequency of depressive and mixed episodes; and 4) comorbidities including substance abuse, anxiety, metabolic and weight concerns, and trauma history. Common medication concerns, including polypharmacy and medication nonadherence, have potential elevate suicide risk ( Benson et al., 2018 ; O’Neill et al., 2019 ; Nery-Fernandes et al., 2012 ; Tsai et al., 2016 ); however, research findings are mixed based on type of medication regarding the association between use of mood stabilizing medications and suicide risk: more consistent findings have been found between the use of lithium and decreased suicide risk ( Benard et al., 2016 ; Collins and McFarland, 2008 ); findings for other mood stabilizers (e.g., divalproex, valproate, olanzapine, quetiapine, carbamazepine) showed minimal to no impact on reducing suicide risk ( Chen et al., 2019 ; Collins and McFarland, 2008 ; Hayes et al., 2016 ; Tsai et al., 2016 ). 1.3. Overview of the current study While research has documented an increase in the risk of suicide and suicide mortality among individuals with either pain or bipolar disorder, little research has looked at suicide rates and mortality information, as well as additional factors that may affect these rates, among individuals with comorbid pain and bipolar disorder. The literature is especially limited when considering pain – versus bipolar disorder – as the primary condition of interest. The aim of this study was to examine suicide rates and related correlates among veterans with pain and comorbid bipolar disorder. Comparing those who died by suicide to those who did not, we hypothesized that those who died by suicide would have higher pain severity ratings, and that risk will be impacted by key correlates including age (older), race (White), gender (male), additional mental health and substance use comorbidities, and prescription medications (opioids, benzodiazepines). 2. Methods 2.1. Study design We conducted a retrospective cohort analysis of VHA clinical and administrative data from 2000 to 2015. 2.2. Study population The sample for this study is drawn from a VHA national cohort of over 6-million Veterans diagnosed with a musculoskeletal disorder (MSD) 3 diagnosis. The MSD cohort ( Goulet et al., 2016 ) was designed to allow for both retrospective and prospective analyses and has been updated on a regular basis to enroll additional individuals. Veterans were included in the MSD cohort if they had 1) an MSD diagnosis within their medical record (see Supplement 1 for ICD-9 codes), and 2) two or more outpatient visits for an MSD diagnosis occurring within 18 months of each other or one or more inpatient stays with an MSD diagnosis. This method (two outpatient diagnoses or one inpatient) is more comprehensive/robust than relying on a single outpatient code, as outpatient diagnoses are entered into the electronic health record by healthcare providers at the time of the encounter and inpatient ones by trained professional coders after medical record review. The MSD index date is the date of the individual’s first outpatient or inpatient MSD diagnosis. Refer to Goulet et al. (2016) for a detailed description of the MSD cohort creation. The MSD cohort study is approved by the Human Research Protection Program at the [institution] and has been granted a HIPAA waiver and waiver of informed consent. The current study sample includes individuals with a bipolar disorder diagnosis who were enrolled in the main MSD cohort through September 30, 2015 ( N = 168,021). Overall prevalence of bipolar disorder in the full MSD cohort was 2.4 % (N = 168,021/6,987,674). 2.3. Data sources Administrative and clinical data for the overall cohort have been pulled from the VHA Corporate Data Warehouse and other data sources noted in Key Variables section below. Variables extracted include patient demographic characteristics (i.e., age at MSD index date, sex, race/ethnicity), pain intensity numeric rating scale score on the MSD index date (“baseline”), comorbid medical and mental health conditions at baseline, pharmacy dispenses, healthcare utilization, and death information. 2.4. Key variables 2.4.1. Bipolar diagnosis Bipolar disorder diagnosis was identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM; 296.00–296.06, 296.10–296.16, 296.40–296.46, 296.50–296.56, 296.60–296.66, 296.7, 296.80–296.82, 296.89–296.90, 296.99, and V11). VHA did not use ICD-10 codes until October 1, 2015. Presence of bipolar disorder was identified using the same two outpatient or one inpatient ICD code method as noted for MSD diagnosis above, though the timeframe was one year prior to and up to six months after the MSD index date. The presence of a diagnosis in this time frame around the MSD index date suggests it was likely active and/or actively treated at the time of the MSD diagnosis. The above timeframe was also chosen to allow for sufficient follow-up time to detect suicide deaths, allowing for delays in the reporting of and obtaining data about suicide deaths. 2.4.2. Pain numeric rating scale The cohort data includes the pain intensity numeric rating scale (PNRS; Breivik et al., 2008 ) score for the MSD index date. The PNRS is a global measure of pain that is not attributable to a specific diagnosis. Patients are asked to rate their current pain level using a scale of 0 ( no pain ) to 10 ( worst possible pain ). VHA clinical practice guidelines were in effect at the time of this study which recommended assessing pain via PNRS at routine medical visits. If there were multiple PNRS ratings on the MSD index date, then the highest rating was selected. Any missing or invalid PNRS (i.e., those outside the range of 0 to 10) were classified as missing and reported in a separate category (“not assessed”). Two variables were created based on PNRS data. First, we created a dichotomous (yes/no) variable to evaluate this sample by assessment status (assessed or not assessed). Second, for those with valid PNRS data, we categorized PNRS scores into 4 levels of pain: 0, no pain; 1 to 3, mild pain; 4 to 6, moderate pain; and 7 to 10, severe pain ( Goulet et al., 2016 ; Tan et al., 2008 ). 2.4.3. Suicide Death information was obtained from the VA-DoD Mortality Data Repository (MDR), a joint effort between the VA Office of Mental Health and Suicide Prevention (OMHSP) 4 and the Department of Defense (DoD) 5 to collect mortality data of Veterans and Service Members. The information is gathered from the National Center for Health Statistics’ National Death Index (NDI) and contains mortality information including the underlying leading cause of death, which includes suicide. For this sample, we identified participant suicide by using the external cause of injury frameworks/matrix which is based on ICD-10-CM classification and includes these specific suicide external cause-of-injury codes: X60-X69, X70-X79, X80-X84, U03.0, and Y87.0 ( National Center for Health Statistics, 2015 , 2021 ). 2.4.4. Covariates Covariates were identified based on extant literature and were pulled from the VHA Corporate Data Warehouse. Specific covariates included demographic variables (age, sex, race, marital status, and homelessness), comorbid mental health and substance use disorders (depression, posttraumatic stress disorder, alcohol abuse, illicit drug use), notable psychiatric medications (e.g., mood stabilizers, antidepressants, anticonvulsants, antipsychotics), and pain-related medications (opioids, gabapentin, benzodiazepines). Dichotomous (yes/no) variables were created for each mental health and medication category to indicate whether there was an active diagnosis or a filled outpatient prescription one year before to six months after the MSD index date. 2.5. Data analysis We used descriptive statistics to examine sociodemographic, mental health characteristics, medications, and suicide by whether pain was assessed (yes or no) and then by level of pain among those with a pain assessment (no pain, mild, moderate, severe). We compared differences for pain assessed versus not assessed and then for different levels of pain in bivariate models using chi-square statistics ( Table 1 ). We then created two multi-variate models for pain assessment (Model 1) and level of pain (Model 2), respectively. Given the primary outcome is suicide, we used Poisson regression with log link to estimate the relative risks (RR) and 95 % confidence intervals (CI; Table 2 ). For each model, we examined crude RRs to show level of independent risk for suicide for each covariate (i.e., all sociodemographic variables, mental health/substance use disorders, and medications listed in Table 1 ) based on pain assessment and level. We also examined adjusted RR by including all covariates in both multi-variate models. We used SAS 9.4 for all analyses (SAS institute, Cary, NC). Table 1. Demographic characteristics and suicide mortality based on pain assessment and pain severity level. Variable Not Assessed n = 45,814 (27.27 %) Assessed ( N = 122,207; 72.73 %) p No Pain n = 36,878 (30.18 %) Mild Pain n = 16,588 (13.57 %) Moderate Pain n = 31,144 (24.58 %) Severe Pain n = 37,597 (30.77 %) Age <0.0001 16–40 8457 (18.46 %) 7938 (21.53 %) 4730 (28.51 %) 9504 (30.52 %) 9559 (25.42 %) 41–55 22,449 (49.00 %) 14,182 (38.46 %) 6605 (39.82 %) 13,537 (43.47 %) 18,288 (48.64 %) 56–65 9012 (19.67 %) 8846 (23.99 %) 3705 (22.34 %) 5974 (19.18 %) 7352 (19.55 %) 66–75 3885 (8.48 %) 3767 (10.21 %) 1073 (6.47 %) 1539 (4.94 %) 1721 (4.58 %) ≥76 2011 (4.39 %) 2145 (5.82 %) 475 (2.86 %) 590 (1.89 %) 677 (1.80 %) Sex <0.0001 Male 40,279 (87.92 %) 32,361 (87.75 %) 14,567 (87.82 %) 26,569 (85.31 %) 32,250 (85.78 %) Female 5535 (12.08 %) 4517 (12.25 %) 2021 (12.18 %) 4575 (14.69 %) 5347 (14.22 %) Race <0.0001 White 34,335 (74.94 %) 28,301 (76.74 %) 13,306 (80.21 %) 23,980 (77.00 %) 27,143 (72.19 %) Black 6628 (14.47 %) 4933 (13.38 %) 1525 (9.19 %) 3941 (12.65 %) 6569 (17.47 %) Hispanic 2386 (5.21 %) 1937 (5.25 %) 1002 (6.04 %) 1635 (5.25 %) 2035 (5.41 %) Other 2465 (5.38 %) 1707 (4.63 %) 755 (4.55 %) 1588 (5.10 %) 1850 (4.92 %) Marital status <0.0001 Married 15,546 (33.93 %) 13,909 (37.72 %) 6383 (38.48 %) 11,614 (37.29 %) 12,317 (32.76 %) Unmarried 30,193 (65.90 %) 22,893 (62.08 %) 10,141 (61.13 %) 19,456 (62.47 %) 25,199 (67.02 %) Unknown 75 (0.16 %) 76 (0.21 %) 64 (0.39 %) 74 (0.24 %) 81 (0.22 %) Pain type Low back 8391 (8.32 %) 7589 (20.58 %) 3935 (23.72 %) 8620 (27.68 %) 10,864 (28.90 %) <0.0001 Neck 3229 (7.05 %) 2976 (8.07 %) 1603 (9.66 %) 3488 (11.20 %) 3957 (10.52 %) <0.0001 Index MSD diagnosis location <0.0001 Emergency Department/Urgent Care 6527 (14.25 %) 1742 (4.72 %) 1803 (10.87 %) 4771 (15.32 %) 9938 (26.43 %) Other outpatient 34,012 (74.24 %) 26,884 (72.90 %) 12,836 (77.38 %) 23,106 (74.19 %) 22,582 (60.06 %) Inpatient 5076 (11.08 %) 8078 (21.90 %) 1902 (11.47 %) 3188 (10.24 %) 4966 (13.21 %) Unknown 199 (0.43 %) 174 (0.47 %) 47 (0.28 %) 79 (0.25 %) 111 (0.30 %) Mental health diagnoses Major Depressive Disorder 9966 (21.75 %) 6452 (17.50 %) 2817 (16.98 %) 5579 (17.91 %) 7086 (18.85 %) <0.0001 PTSD 11,853 (25.87 %) 8855 (24.01 %) 4260 (25.68 %) 8998 (28.89 %) 10,982 (29.21 %) <0.0001 Drug Use Disorders 12,386 (27.04 %) 8758 (23.75 %) 3630 (21.88 %) 7739 (24.85 %) 11,896 (31.64 %) <0.0001 Alcohol Use Disorders 13,673 (29.84 %) 9744 (26.42 %) 3887 (23.43 %) 7966 (25.58 %) 11,163 (29.69 %) <0.0001 Medications FDA-approved bipolar medication 32,390 (70.77 %) 25,268 (68.52 %) 10,905 (65.74 %) 20,918 (67.17 %) 26,543 (70.60 %) <0.0001 Antidepressant 33,440 (72.99 %) 26,117 (70.82 %) 11,864 (71.52 %) 23,175 (74.41 %) 28,568 (75.98 %) <0.0001 Anticonvulsant 26,178 (57.14 %) 18,965 (51.43 %) 8417 (50.74 %) 16,701 (53.63 %) 21,520 (57.24 %) <0.0001 Antipsychotic 21,540 (47.02 %) 17,700 (48.00 %) 7254 (43.73 %) 14,269 (45.82 %) 19,312 (51.37 %) <0.0001 Opioids 4199 (9.17 %) 1305 (3.54 %) 812 (4.90 %) 2781 (8.93 %) 6334 (16.85 %) <0.0001 Gabapentin 2743 (5.99 %) 1353 (3.67 %) 661 (3.98 %) 1417 (4.55 %) 2100 (5.59 %) <0.0001 Benzodiazepine 7791 (17.01 %) 4919 (13.34 %) 2196 (13.24 %) 4289 (13.77 %) 5948 (15.82 %) <0.0001 Suicide Mortality 450 (0.98 %) 287 (0.78 %) 115 (0.69 %) 240 (0.77 %) 293 (0.78 %) 0.0004 Open in a new tab MSD = musculoskeletal disorder. PTSD = posttraumatic stress disorder. FDA = Federal Drug Administration. Table 2. Relative risk of suicide mortality by pain, demographic and clinical characteristics based on pain assessment and level of pain severity in Veterans within Musculoskeletal Disorder (MSD) Cohort with comorbid bipolar disorder diagnosis. Variable (covariates) Assessed (yes, no) N = 168,021 Level of pain N = 122,207 Crude RR Adjusted RR 95 % CI p Crude RR Adjusted RR 95 % CI p Assessed 0.79 1.06 [1.02, 1.09] 0.0017 – – Not assessed Ref Ref Ref – – Pain severity No pain – – Ref Ref Ref Mild pain – – 0.96 0.99 [0.93, 1.06] 0.8056 Moderate pain – – 1.05 1.10 [1.05, 1.16] 0.0002 Severe pain – – 1.04 1.06 [1.01, 1.12] 0.0177 Age 16–40 Ref Ref Ref Ref Ref Ref 41–55 0.93 0.86 [0.83, 0.90] <0.0001 1.00 0.90 [0.86, 0.94] <0.0001 56–65 0.78 0.78 [0.74, 0.82] <0.0001 0.88 0.87 [0.82, 0.92] <0.0001 66–75 0.60 0.63 [0.58, 0.69] <0.0001 0.65 0.65 [0.58, 0.72] <0.0001 ≥76 0.66 0.75 [0.66, 0.86] <0.0001 0.86 0.94 [0.82, 1.08] 0.3878 Sex Male Ref Ref Ref Ref Ref Ref Female 0.57 0.56 [0.53, 0.59] <0.0001 0.46 0.46 [0.42, 0.49] <0.0001 Race White Ref Ref Ref Ref Ref Ref Black 0.32 0.30 [0.28, 0.32] <0.0001 0.35 0.33 [0.30, 0.36] <0.0001 Hispanic 0.63 0.62 [0.57, 0.68] <0.0001 0.71 0.70 [0.64, 0.78] <0.0001 Other 2.65 2.63 [2.51, 2.77] <0.0001 2.44 2.49 [2.34, 2.64] <0.0001 Marital status Married Ref Ref Ref Ref Ref Ref Unmarried 1.50 1.37 [1.32, 1.42] <0.0001 1.55 1.43 [1.37, 1.49] <0.0001 Pain type Low Back 1.07 1.03 [0.99, 1.07] 0.1089 1.05 1.03 [0.99, 1.07] 0.2015 Neck 1.09 1.06 [1.01, 1.12] 0.0271 1.06 1.04 [0.98, 1.11] 0.1962 Index MSD diagnosis location Emergency Department/Urgent Care Ref Ref Ref Ref Ref Ref Inpatient 1.57 1.44 [1.36, 1.52] <0.0001 1.74 1.60 [1.49, 1.71] <0.0001 Other outpatient 0.96 1.06 [1.01, 1.10] 0.0208 1.03 1.13 [1.07, 1.20] 0.3082 Mental health diagnoses (yes) Major Depressive Disorder 1.41 1.30 [1.25, 1.35] <0.0001 1.37 1.25 [1.19, 1.30] <0.0001 PTSD 0.79 0.68 [0.65, 0.71] <0.0001 0.77 0.67 [0.64, 0.71] <0.0001 Drug Use Disorders 1.46 1.18 [1.13, 1.23] <0.0001 1.50 1.22 [1.16, 1.28] <0.0001 Alcohol Use Disorders 1.51 1.20 [1.15, 1.25] <0.0001 1.49 1.12 [1.07, 1.17] <0.0001 Medications Any FDA-approved bipolar medication 1.51 1.24 [1.18, 1.30] <0.0001 1.59 1.29 [1.22, 1.37] <0.0001 Antidepressant 1.37 1.20 [1.15, 1.25] <0.0001 1.29 1.15 [1.10, 1.21] <0.0001 Anticonvulsant 1.26 1.03 [1.00, 1.07] 0.0780 1.27 1.04 [1.00, 1.09] 0.0416 Antipsychotic 1.42 1.18 [1.13, 1.22] <0.0001 1.47 1.18 [1.12, 1.23] <0.0001 Opioids 1.26 1.18 [1.12, 1.24] <0.0001 1.13 1.07 [1.00, 1.14] 0.0382 Gabapentin 1.44 1.23 [1.16, 1.32] <0.0001 1.34 1.16 [1.07, 1.26] 0.0002 Benzodiazepines 1.61 1.54 [1.48, 1.60] <0.0001 1.68 1.60 [1.53, 1.68] <0.0001 Open in a new tab RR = relative risk. CI = confidence interval for adjusted RR. MSD = musculoskeletal disorder. PTSD = posttraumatic stress disorder. FDA = Federal Drug Administration. 3. Results The sample of Veterans (comorbid pain and bipolar disorders) was predominantly male (86.91 %), white (75.62 %) and unmarried (64.21 %). The majority were under age 55 with 23.92 % ( n = 40,188) between 18 and 40 years and 44.67 % ( n = 75,061) between 41 and 55 years. MDR death information was available for 20.32 % ( n = 34,143) of the bipolar disorder cohort. Among those who died, 0.82 % died by suicide ( N = 1385/168,021) with 0.50 % ( N = 110) of females and 0.87 % ( N = 1275) of males dying by suicide. Demographic factors that were associated with a reduced risk of suicide, regardless of pain assessment, include identifying as female, Black or Hispanic, and being married. PNRS on the MSD index date was assessed in 72.73 % of this sample, thus 27.27 % did not have a valid pain assessment (PNRS) on their MSD index date. Those who were not assessed for pain ( N = 45,814) tended to be younger and male, and the majority (65.90 %) were more likely to have been unmarried. A greater proportion of those not assessed for pain were also more likely to have been diagnosed with a major depressive disorder (21.75 %) or a drug (27.04 %) or alcohol use disorder (29.84 %) and had filled prescriptions for gabapentin (5.99 %) or benzodiazepines (17.01 %). Among those with valid PNRS ( N = 122,207), 30.18 % reported no pain, while 25.48 % reported moderate and 30.77 % reported severe pain. In bivariate models of pain and suicide ( Table 1 ), a greater proportion of people who were not assessed for pain died by suicide (0.98 %) as compared to those who had valid PNRS ratings (range of 0.69 % to 0.78 % depending on pain level); this is also reflected in the crude relative risk of dying by suicide being higher in the not assessed group ( Table 2 ). However, the relative risk of dying by suicide was greater in those assessed versus not assessed when covariates were included in the model (Model 1, Table 2 ). Among those assessed for pain, those with moderate, or severe levels of pain were at higher risk of dying by suicide compared to those with no pain or mild pain (Model 2). The presence of major depressive disorder and substance use disorders were associated with elevated risk of suicide regardless of pain assessment; the risk was highest for those diagnosed with major depressive disorder and alcohol use disorder in the model for assessment status (Model 1). Those with a posttraumatic stress disorder (PTSD) diagnosis had a lower risk of death by suicide in both models compared to those with no PTSD diagnosis. The presence of different prescription medications overall was associated with increased risk of suicide, and the risk was highest for Veterans with an outpatient benzodiazepine prescription in both models. The greatest difference in the risk of suicide in the model of pain assessment (Model 1) versus level of pain (Model 2) was for opioids, with the risk seeming greater in the model of pain assessment compared to the model of level of pain (adjusted RR = 1.18 versus 1.07, respectively). While both models show that having an opioid prescription was associated with greater risk of suicide mortality, the risk was greater for those that were not assessed relative to those who were assessed for pain. 4. Discussion This retrospective study examined Veterans with a musculoskeletal diagnosis and a bipolar disorder diagnosis at baseline entry into the cohort. Veterans with bipolar disorder and Veterans with pain are each disproportionately affected by suicide (e.g., Ilgen et al., 2013 ; Schaffer 2013). We found a high rate of suicide (0.82 %) in this pain cohort among Veteran’s diagnosed with bipolar disorder. This rate is significantly higher than what has been reported by VHA; in 2015, the overall rate of suicide in VHA users was 37.5 per 100,000 (0.04 %), with Veterans with bipolar disorder (131.0/100 k) or opioid use disorder (119.1) showing the highest rates at approximately x per 100,000 (0.12 %) for both groups ( OMHSP, 2023 ). A study using national VHA data (2000–2006) found rates of suicide mortality across pain conditions to be approximately 0.34 % ( Ilgen et al., 2010c ), which again is higher than the VHA average rate but lower than what was found in this study sample. Thus, it is likely that the compounding burden of both bipolar disorder and pain are leading to the increased suicide mortality rates found in this study. We also explored whether pain as measured by the PNRS was related to suicide in Veterans diagnosed with pain and bipolar disorder. We found that more than a quarter of Veterans were not assessed for pain on their MSD index date, which was similar to what was seen in the overall MSD cohort ( Goulet et al., 2016 ). After controlling for confounding factors, the two models showed that those assessed for pain had a slightly greater relative risk of suicide than those who were not. There is no literature to suggest that pain assessment (or lack thereof) may be directly related to suicide mortality. Assessment for pain may be associated with characteristics that are also associated with a higher risk for suicide. For example, a greater proportion of those who were not assessed were younger, unmarried and had diagnoses of major depressive, drug, and/or alcohol use disorders. These conditions could be the focus of clinical visits and therefore overshadow conversations about pain. Additionally, individuals in greater distress (i.e., higher risk for suicide) may also be seeking care that would allow for more thorough or frequent assessment of pain and other risk factors; that is, they may be more likely to seek out care or more likely seen in more intense care settings (e.g., emergency room or inpatient care). In the group with pain assessments, there is a signal of increased risk for suicide. Among those assessed, moderate and severe pain were associated with slightly higher rates of suicide risk. This is consistent with the literature demonstrating that suicide mortality is related to greater pain severity ( Ilgen et al., 2010c ). However, what is interesting about this study’s findings is that mild pain – relative to other pain categories including no pain – conferred the lowest risk. Research on pain experiences in individuals with bipolar disorder has shown that individuals may feel disconnected from or feel less pain when experiencing manic episodes ( Boggero and Cole, 2016 ; Travaglini et al., 2020 ). In this sample of individuals with pain and bipolar disorder, it may be the case that increased psychiatric symptoms or other associated concerns could lead to a lower pain rating despite potentially high levels of distress and suicidality. 4.1. Clinical implications Pain, especially chronic pain and/or pain that has a significant, negative impact on functioning and quality of life, is a risk factor for suicide. Additionally, individuals with bipolar disorder are at higher risk for suicide. With high comorbidity rates of pain and bipolar disorder in Veteran populations, it is important that providers are aware of this heightened risk and take steps to identify, assess, and manage contributing risk factors. Pain screening in both medical and mental health settings is important in individuals diagnosed with bipolar disorder, because it may be related to a subsequent suicide. Providers may want to prioritize prevention efforts following events such as new onset pain conditions to reduce pain related distress and reduce potential conversion to chronic pain. Brief behavioral and psychological approaches have been introduced into acute care settings to reduce distress and improve treatment outcomes ( Darnall, 2016 ). Additionally, consistent monitoring of pain severity is warranted, especially with chronic pain, as moderate or severe pain in individuals with both painful conditions and bipolar disorder can affect risk for suicide. Within mental health settings, providers can screen for pain and assess its impact on quality of life and functioning, as pain can further worsen the individuals’ overall quality of life and functioning ( Travaglini et al., 2020 ). While referring individuals with pain concerns to primary care and other medical providers is often appropriate, mental health providers can also address an individuals’ pain management needs by integrating pain psychotherapies such as Cognitive Behavioral Therapy for Chronic Pain (CBT-CP), Acceptance and Commitment Therapy for Chronic Pain (ACT-CP), and mindfulness-based activities into their work with Veterans with bipolar disorder ( Edmond et al., 2019 ). Psychiatric providers can also consider medications that may be beneficial to managing both pain and mood symptoms, and may be uniquely positioned to also be mindful of drug-drug interactions when considering medications to manage both conditions (e.g., potential lithium toxicity with use of nonsteroidal anti-inflammatory drugs, NSAIDS; Hassan et al., 2013 ). To effectively reduce suicide risk in this population, care coordination – or, ideally, integrated care – is essential. Even in settings such as the VA, that is the United States’ largest “integrated health care network,” siloes of care still exist, and patients like those with bipolar disorder and other serious mental illnesses that are seen as challenging or difficult to treat are often not provided equal access to services to address all of their health care needs ( Travaglini et al., 2023 ). Improving access to pain management services and better care coordination is needed to ensure that the medical and mental health needs of Veterans with bipolar disorder are being appropriately addressed. 4.2. Limitations Data were obtained through medical record information and included administrative coded data only. As such, there could be potential bias for underestimation of suicide cases based on information provided within the NDI. In addition, over a quarter of the sample were missing pain intensity ratings on their MSD index and this missing information could have changed results. Diagnoses could not be verified through formal medical or psychodiagnostic evaluation, nor could medical record information reveal mood symptom severity around the time of MSD index date. Prescription data only shows what prescriptions were filled within VHA; it did not include non-VA medications filled or what medications were taken. It is also difficult to verify for which condition medications were prescribed (e.g., antidepressants could be prescribed for mood and/or pain), which could limit interpretation of how these medications and their intended uses contributed to suicide risk. Lack of control group could also affect interpretation of findings. In spite of these limitations, the availability of PNRS screens, and the wealth of data from this large, well-described electronic record-based cohort provides information that many studies will not have. 5. Conclusions Veterans with comorbid pain and bipolar disorder are at significantly elevated risk for suicide mortality. However, the risk factors for suicide among persons with bipolar disorder are complex and likely multifactorial. Thus, pain screening is important in individuals diagnosed with bipolar disorder, because it may be related to a subsequent suicide. Providers may want to prioritize prevention efforts following events such as new onset pain conditions. Additionally, consistent monitoring of pain severity is warranted, especially with chronic pain, as moderate or severe pain in individuals with both painful conditions and bipolar disorder can affect risk for suicide. Further research is recommended to consider differences in acute versus chronic pain experiences and how course of mental illness may affect risk. Supplementary Material Supplemental Table 1 NIHMS2169845-supplement-Supplemental_Table_1.docx (46.8KB, docx) Supplementary data to this article can be found online at https://doi.org/10.1016/j.jad.2024.10.028 . Acknowledgements We would like to thank Drs. Cynthia Brandt and Brenda Fenton for their feedback in support of this manuscript. The opinions expressed here are those of the authors and do not represent the official policy or position of the US Department of Veterans Affairs. Funding This work was supported by the Veterans Health Administration Health Services Research & Development grants IIR 16-262 (Grant # 1I01HX002308-01A1; PIs: Goulet and Zeng). The funding source did not contribute to the preparation of this manuscript. Footnotes 2 VHA = Veterans Health Administration. 3 MSD = musculoskeletal disorder. 4 OMHSP = Office of Mental Health and Suicide Prevention. 5 DoD = Department of Defense. CRediT authorship contribution statement Erica A. Abel: Writing – review & editing, Writing – original draft, Methodology, Formal analysis, Conceptualization. Letitia E. Travaglini: Writing – review & editing, Writing – original draft, Methodology, Conceptualization. Jennifer L. Snow: Writing – review & editing, Formal analysis. Joseph L. 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