Pain and Depression: A Systematic Review

IsHak, Waguih William; Wen, Raymond Y; Naghdechi, Lancer; Vanle, Brigitte; Dang, Jonathan; Knosp, Michelle; Dascal, Julieta; Marcia, Lobsang; Gohar, Yasmine; Eskander, Lidia; Yadegar, Justin; Hanna, Sophia; Sadek, Antonious; Aguilar-Hernandez, Leslie; Danovitch, Itai; Louy, Charles

doi:10.1097/hrp.0000000000000198

Cited by 361 publications

(207 citation statements)

References 47 publications

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“…11 Our bidirectional analyses, with genetic liability for prescription opioid use as an outcome, point to genetic liability for MDD but not ASRD as a possible causal risk factor of opioid use in psychiatric populations. Depression severity has been shown to be associated with increasing likelihood of misusing opioid medications for nonpain symptoms and selfincreasing opioid dosage 58 and up to 30% of long-term opioid users who have MDD qualify for moderate-to-severe OUD, 15,59 suggesting that targeting opioid use prevention for patients with MDD may help mitigate the US opioid epidemic. 1,10 Given more than half of individuals with OUD have comorbid MDD, 10 the increased use of opioids by individuals with MDD may be owing to self-medication of social or emotional pain, 11 suggesting that the development of thera-peutic interventions with minimal risk targeted at endogenous opioid dysregulation represents another important prevention opportunity.…”

Section: Discussionmentioning

confidence: 99%

Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders

2021

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IMPORTANCEGrowing evidence suggests that prescription opioid use affects depression and anxiety disorders; however, observational studies are subject to confounding, making causal inference and determining the direction of these associations difficult.OBJECTIVE To investigate the potential bidirectional associations between the genetic liability for prescription opioid and other nonopioid pain medications and both major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD) using genetically based methods. DESIGN, SETTING, AND PARTICIPANTSWe performed 2-sample mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) to assess potential associations of self-reported prescription opioid and nonopioid analgesics, including nonsteroidal anti-inflammatories (NSAIDs) and acetaminophen-like derivatives use with MDD and ASRD. The GWAS data were derived from participants of predominantly European ancestry included in observational cohorts. Data were analyzed February 20, 2020, to May 4, 2020.MAIN OUTCOMES AND MEASURES Major depressive disorder, ASRD, and self-reported pain medications (opioids, NSAIDs, anilides, and salicylic acid). RESULTSThe GWAS data were derived from participants of predominantly European ancestry included in the population-based UK Biobank and Lundbeck Foundation Initiative for Integrative Psychiatric Research studies: approximately 54% of the initial UK Biobank sample and 55.6% of the Lundbeck Foundation Initiative for Integrative Psychiatric Research sample selected for the ASRD GWAS were women. In a combined sample size of 737 473 study participants, single-variable MR showed that genetic liability for increased prescription opioid use was associated with increased risk of both MDD (odds ratio [OR] per unit increase in log odds opioid use, 1.14; 95% CI, 1.06-1.22; P < .001) and ASRD (OR, 1.24; 95% CI, 1.07-1.44; P = .004). Using multivariable MR, these opioid use estimates remained after accounting for other nonopioid pain medications (MDD OR, 1.14; 95% CI, 1.04-1.25; P = .005; ASRD OR, 1.30; 95% CI, 1.08-1.46; P = .006), and in separate models, accounting for comorbid pain conditions. Bidirectional analyses showed that genetic liability for MDD but not ASRD was associated with increased prescription opioid use risk (OR, 1.18; 95% CI, 1.08-1.30; P < .001). These estimates were generally consistent across single-variable and multivariable inverse variance-weighted (MV-IVW) and MR-Egger sensitivity analyses. Pleiotropy-robust methods did not indicate bias in any MV-IVW estimates. CONCLUSIONS AND RELEVANCEThe findings of this mendelian randomization analysis suggest evidence for potential causal associations between the genetic liability for increased prescription opioid use and the risk for MDD and ASRD. While replication studies are necessary, these findings may inform prevention and intervention strategies directed toward the opioid epidemic and depression.

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Section: Discussionmentioning

confidence: 99%

Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders

2021

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“…Serotonin noradrenaline reuptake inhibitors (SNRIs; e.g., duloxetine) and selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, sertraline) are commonly used antidepressants for the treatment of comorbid chronic pain and depression (60). Other antidepressant options include tricyclic antidepressants (TCAs) such as amitriptyline (61,62).…”

Section: Introductionmentioning

confidence: 99%

“…Other antidepressant options include tricyclic antidepressants (TCAs) such as amitriptyline (61,62). While these medications have been found to reduce the symptoms of both depression and pain partially, no significant differences in efficacy between them have been established so far (63), thus further research is required (60,64). For example, the efficacy of TCAs against other antidepressants for the treatment of comorbid chronic pain and depression remains unclear due to a lack of rigorous studies (35,65,66).…”

Section: Introductionmentioning

confidence: 99%

Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness

et al. 2021

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The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37–2.54]), recent suicide attempt (OR = 1.88 [1.14–3.09]), higher use of tobacco (OR = 1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68–0.83]), escitalopram (OR = 0.75 [0.67–0.85]) and venlafaxine (OR = 0.78 [0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30–0.67]), escitalopram (OR = 0.45 [0.27–0.74]) and citalopram (OR = 0.32 [0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.

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“…As the number of MM conditions increase from one to five, the proportion of residents reporting mild pain decreases to zero among residents with 5 MM conditions. Several factors are known to contribute to pain intensity and frequency; most notably, depression and anxiety (see 43 IsHak, Wen, Naghechi, Vanle, Dang, Knsop et al, 2018 for a recent review), musculoskeletal problems, 40,44 and cardiovascular diseases; 45 unfortunately, the interaction between chronic pain and CCD is not well understood. There is evidence, however, that management of CCD patients can become increasingly more challenging when patients also experience chronic pain, due to complications associated with medication dosing and interactions among multiple diseases.…”

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confidence: 99%

<p>Association Between Multimorbid Disease Patterns and Pain Outcomes Among a Complex Chronic Care Population in Canada</p>

Ferguson¹,

Svendrovski²,

Katz³

2020

JPR

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Purpose: Disease multimorbidity and pain is a complex, yet common, problem for the aging population, and a significant burden on the health-care systems around the world. Despite this, disease comorbidity and the association with pain in a complex chronic care population is not well understood. This study examined the most prevalent disease combinations and their association with pain. Patients and Methods: The study initially included 139,920 residents, aged 18-101 years, admitted to publicly funded hospital facilities for complex chronic care in Canada between the years 2006 and 2016. Data were acquired through the Canadian Institute for Health Information (CIHI) Facility-Based Continuing Care Reporting System (CCRS). Descriptive and chi-square statistics were used to summarize and compare the sample characteristics. Binary logistic regression analyses were used to examine the association between multimorbid disease categories and pain outcomes. Results: The sample consisted of 139,573 residents (57% female), mostly older (mean age = 77.32 years), married (40%), or widowed (36%). Residents took an average of 11.9 medications and 77% were using analgesic medications. On average, residents had diagnoses from 3.06 disease categories (SD = 1.43). Heart/circulation diseases were the most prevalent among the sample (73%), with neurological second (46%) and musculoskeletal third (44%). Overall, 73% of residents reported pain, with 43% reporting moderate pain severity. Residents with multiple disease categories were more likely to report the presence of pain (OR = 1.08, 95% CI: 1.07-1.08, p < 0.001), with each additional disease category associated with an 8% increase in the odds of reporting pain. Conclusion: The findings from this study help identify common comorbid disease patterns related to pain in an institutionalized, complex chronic care population. This information contributes to both the pain and multimorbidity literature, and is invaluable for creating care plans to meet the demands of a challenging population.

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Pain and Depression: A Systematic Review

Cited by 361 publications

References 47 publications

Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders

Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders

Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness

<p>Association Between Multimorbid Disease Patterns and Pain Outcomes Among a Complex Chronic Care Population in Canada</p>

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