Historically, the simultaneous use of opioids and benzodiazepines has been associated with respiratory depression and increased risk of death.1,2 Recent studies have indicated that this combination of medications is commonly prescribed in the workers’ compensation system.3,4 Multiple safety announcements from the US Food and Drug Administration regarding the risks associated with the use of opioids and benzodiazepines in combination have been disseminated to the medical community.5–7 When reviewing the history of 11,394 lost time claims from Louisiana Workers’ Compensation Corporation from 1999 to 2002, Johns’ Hopkins University (JHU) researchers uncovered a distinctive prescribing pattern. They found that the average benzodiazepine dosage increased up to 3 years post-injury then plateaued, however claim costs continued to increase. In addition, the average opioid dosage continued to increase year after year through claim closure. They concluded that the addition of benzodiazepines to an opioid treatment regimen was associated with increased workers’ compensation costs.4 The JHU team conducted another study on the relationship between the use of psychotropic and opioid medications with workers’ compensation disability and costs on the same cohort. The multivariate logistic regression revealed that the odds of having final claim costs in excess of $100,000 when antidepressants were prescribed was 2.93 (95% CI: 2.43 to 3.53) when controlling for age, sex, marital status, attorney involvement, spinal surgeries, and use of opioids/hypnotics/antipsychotics/anti-anxiety agents.3
The Accident Fund (AF) Group had previously identified the risk of high medical cost and claim duration when opioids were prescribed in 2012.8 Subsequently, papers began to appear suggesting that anti-depressant medication in combination with opioids is a recommended approach to treating chronic pain. Cymbalta (a selective serotonin and norepinephrine reuptake inhibitor antidepressant) received US Food and Drug Administration approval for treating musculoskeletal pain.7
AF Group, a workers’ compensation insurance carrier, manages workers’ compensation claims across the United States and contains a database of detailed medication data including opioid and psychoactive drugs such as benzodiazepines and anti-depressants. This database was used in this study. The objective of the study was to quantify the costs associated with treating workplace injuries while concurrently treating psychosocial and pain issues that arose out of the injury or predated it. We used combinations of anti-depressants and opioid prescriptions as proxies for comorbid psychosocial and pain diagnoses.
This analysis included 22,383 work-related, indemnity claims from AF Group, a workers’ compensation insurance carrier operating as Accident Fund Insurance Company of America, United Heartland, Third Coast Underwriters, and CompWest Insurance Company. Claims (more than 3 days of missed work) reported between 2008 and 2013 that were followed until December 31, 2017 were included in the analysis with the following criteria: at least 3 years of development, at least 1 day of temporary total disability (TTD) benefits, and a non-catastrophic claim (eg, less than $1 million expected total incurred). All claims were evaluated 3 years after the date of the report of the claim. Because we included claims with injury dates between 2008 and 2013 with follow-up to Dec 31, 2017, the shortest claim development period in this cohort was 4 years.
Workers’ compensation claims data and prescription medication data from the AF Group database system was used in the study. The prescription of opioids, antidepressants, and benzodiazepines were evaluated for the first 3 years after the date of the injury being reported (Appendix A, http://links.lww.com/JOM/A530). Chronic pain was identified via International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes 338.2, 338.21, 338.22, 338.28, 338.29, 338.3, and 338.4.
Medical Complexity Score
To control for known risk factors associated with high severity claims we utilized the medical complexity scoring system that was used in a previous study.9 This metric, uses a mix of elastic net regression10 and stochastic gradient boosting.11 The predictive model targets claim duration and incorporates the following independent variables: age at accident, nature of injury, primary body part injured, cause of injury, claimant's benefit state, claimant's class code, and claimant's International Classification of Diseases, Ninth Revision codes. On a randomly chosen, 30% validation set, the Spearman Correlation between predicted and actual values was 0.64. The final score is calculated by mapping each prediction to a 1 to 100 scale by way of one percentile groupings, whereby one represents the lowest medical complexity and 100 represents the highest.
Descriptive statistics were used to classify the medication groups by different combinations of opioid, benzodiazepines, and anti-depressant medications. A summary of the frequency of claims, closure rate, average medical cost, and average total claim costs by these drug combination groups are examined from the date of report to the end of the follow-up period (December 31, 2017).
We utilized a multivariable logistic regression model to evaluate the association of anti-depressant prescription with open claims at the end of follow-up, when controlling for opioid and benzodiazepine prescriptions, age at injury, medical complexity, and the number of years of claim development. A linear regression model was used to analyze the increase in medical and total claim costs associated with anti-depressant medications (controlling for the same set of confounders). SAS software (SAS Institute, Inc., Cary, NC) was used for all analysis.12
Table 1 presents the number and average costs related to different combinations of the three medication groups. Out of 22,383 indemnity claims, 5201 claims (23.2%) were never prescribed opioid, benzodiazepines, and anti-depressant medications during the first 3 years, while 13,564 claims (60.6%) were prescribed opioids only. All other prescriptions (one medication only and combinations) represented the remainder of the claim population. The proportions of patients prescribed anti-depressants and benzodiazepine, only was 0.1% and 0.5%, respectively. Claims with prescriptions for all drug classes represented 3.4% of claims. The slowest claim closure rate occurred among claimants with prescriptions for all three types of medications (58.3%), followed by claims with both opioid and anti-depressant (64.8%) prescriptions. The group without any drugs had the highest closure rate (91.8%) followed by the group with only opioid (89.1%) prescriptions.
The average medical costs for claims with opioids alone were $28,563 whereas the combination of opioids and benzodiazepines was $53,366; this combination resulted in a slower closure rate of 75.8% (compared with 89.1% for opioids alone). We observed unexpected results when examining anti-depressant use and opioid use. This combination resulted in higher average medical costs ($64,507) and had the second slowest closure rate (64.8%) compared with all other medication combinations. When evaluating claims with opioids, benzodiazepines, and anti-depressants the average medical costs were the highest at $93,667 and had the lowest closure rate at 58.3%. Figure 1 shows the closure rate by the various medication combinations. Figures 2 and 3 show the medical and total claim cost by medication combinations, respectively. The more drug types prescribed the lower, the closure rate, and the higher the cost.
Table 2 shows the association between prescribed medications and the probability of remaining open. The odds ratio (OR) for not closing at the end of study for anti-depressant was 2.24 (95% CI: 2.00 to 2.51), while for opioid 1.14 (95% CI: 1.02 to 1.27) and for benzodiazepines 1.38 (95% CI: 1.23 to 1.54), respectively. This suggests that anti-depressants had the highest independent impact on return to work, compared with opioid and benzodiazepines. Having anti-depressants prescribed was associated with an additional $22,318 in medical cost and $50,911 in total claim cost, respectively (Tables 3 and 4). In addition, anti-depressant prescriptions were associated with the greatest increase in overall claim costs.
Previous studies involving the workers’ compensation system have demonstrated a relationship between opioid medication prescribing and escalating medical costs as well as increased claim duration.3,4,13–17 This study was conducted to evaluate the impact of benzodiazepines and anti-depressants in combination with opioids on workers’ compensation claim cost and closure rates. We found that prescriptions for more psychotropic drugs in multiple treatment classes resulted in overall higher claim costs and delayed claim closures. As expected, claims without any of the medication groups studied had the lowest cost ($19,604 vs $93,667) and highest closure rate (91.8% vs 58.3%). This information expands on the relationships reported by Tao et al3 who found that claims without opioid prescriptions or psychotropic drugs had the lowest average paid costs with the shortest claim duration.
The overall directions of our findings were expected. It is logical to assume that injured workers who are experiencing a significant amount of pain or suffering from depression or anxiety will require more medical services than injured workers not experiencing such symptoms or psychosocial disorders. Our findings are consistent with observations from studies in the general medical literature investigating the longitudinal cost of medical care for individuals with psychological disorders.18–23 The prevalence of cardiovascular, respiratory, endocrine, and many other disorders are higher in patients with mental disorders than those without. As such, the cost of simultaneously treating psychiatric conditions and physical illness is associated with comparatively higher medical care costs.22 While our findings were expected, the magnitude of the cost differences associated with anti-depressant medications did surprise us.
Perhaps the most interesting finding from this study is the relationship between anti-depressant prescriptions on claim closure and costs. Even when controlling for age, chronic pain, medical complexity, and claim development (years), anti-depressant claims to a greater degree, were more likely to remain open at the end of the study period. The effects on total paid costs associated with anti-depressant prescription were greater in magnitude compared with all other drug classes. This finding is similar to the study by Tao et al17 who observed that anti-depressant prescriptions were nearly three times as likely to result in a claim in excess of $100,000.
While this analysis focuses on a large cohort of 22,383 claims (with at least 3 years of development), there are several limitations to this study. Information regarding comorbid conditions and medication use prior to injury (compensable by the workers’ compensation system) was not available. Therefore, criteria for temporality cannot be satisfied. Prior opioid, anti-depressant, and benzodiazepine use for other pre-existing medical conditions may influence assessed claim outcomes, particularly among high-dose opioid claimants.12,13 These data were not available. In addition, claimants with newly developed or prior complex psychosocial issues tend to have delayed return-to-work. While prescriptions for the assessed medications may serve as a proxy for chronic pain and/or mental health diagnoses, prior diagnoses for mental illness was not available to study these associations directly. Additional studies will be necessary to better understand if specific classes of anti-depressants result in different clinical and cost trajectories.
The Centers for Disease Control and Prevention opioid guidelines for chronic pain published in 2017 recommended the reduction of the number and strength of opioid prescriptions.19 This effort has highlighted the need for alternative, non-opioid treatments for chronic pain. Anti-depressants have been considered an efficacious medication in combination with opioids to improve clinical outcomes. Our results show that the addition of anti-depressants to opioids, magnifies the association between delayed claim closure and higher overall cost of this research will assist nurse claim mangers in recognizing the impact of behavioral issues and psychotropic medications on workers’ compensation claim outcomes. It will also allow adjusters to recognize that significantly more resources are required to address the treatment needs of patients with comorbid behavioral conditions. It will also alert claims administrators that the presence of anti-depressant medications on a claim is an indicator of potentially costly claim development. In addition, careful consideration should be given when providers are utilizing opioids, benzodiazepines, and anti-depressants in combination.
1. Cheng M, Sauer B, Johnson E, et al. Comparison of opioid
-related deaths by work-related injury. Am J Ind Med
2. Jones JD, Mogali S, Comer SD. Polydrug abuse: a review of opioid
and benzodiazepine combination use. Drug Alcohol Depend
3. Tao XG, Lavin RA, Yuspeh L, et al. The association of the use of opioid
and psychotropic medications with workers’ compensation
claim costs and lost work time. J Occup Environ Med
4. Lavin RA, Tao XG, Yuspeh L, et al. Impact of the combined use of benzodiazepines
and opioids on workers’ compensation
claim cost. J Occup Environ Med
5. Barry DT, Sofuoglu M, Kerns RD, et al. Prevalence and correlates of co-prescribing psychotropic medications with long-term opioid
use nationally in the Veterans Health Administration. Psychiatry Res
6. Syrowatka A, Chang SL, Tamblyn R, et al. Psychotropic and opioid
medication use in older patients with breast cancer across the care trajectory: a population-based cohort study. J Natl Compr Canc Netw
8. White JA, Tao X, Talreja M, et al. The effect of opioid
use on workers’ compensation
claim cost in the State of Michigan. J Occup Environ Med
9. White JA, Tao X, Artuso RD, et al. Effect of physician-dispensed medication on workers’ compensation
claim outcomes in the state of Illinois. J Occup Environ Med
10. Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw
11. Friedman J, Friedman JH. Stochastic gradient boosting. Comput Stat Data Anal
12. SAS. SAS/ACCESS® 9.4 Cary, NC: SAS Institute Inc.
13. Bernacki EJ, Yuspeh L, Lavin R, et al. Increases in the use of opioids to treat acute and chronic pain in injured workers, 1999–2009. J Occup Environ Med
14. Bernacki EJ, Yuspeh L, Tao X. Determinants of escalating costs in low risk workers’ compensation
claims. J Occup Environ Med
15. Lavin RA, Tao XG, Yuspeh L, et al. Relationship between opioid
prescribing patterns and claim duration and cost. J Occup Environ Med
16. Tao XG, Lavin RA, Yuspeh L, et al. Impact of the combined use of opioids and surgical procedures on workers’ compensation
cost among a cohort of injured workers in the state of Louisiana. J Occup Environ Med
17. Tao XG, Lavin RA, Yuspeh L, et al. Natural history of opioid
dosage escalation post-injury: a cohort study of injured workers in the State of Louisiana. J Occup Environ Med
18. De Hert M, Cohen D, Bobes J, et al. Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level. World Psychiatry
19. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain–United States. JAMA
20. Gramaglia C, Gambaro E, Bartolomei G, et al. Increased risk of metabolic syndrome in antidepressants users: a mini review. Front Psychiatry
21. Jansen L, van Schijndel M, van Waarde J, et al. Health-economic outcomes in hospital patients with medical-psychiatric comorbidity: a systematic review and meta-analysis. PLoS One
22. Katon WJ, Lin E, Russo J, et al. Increased medical costs of a population-based sample of depressed elderly patients. Arch Gen Psychiatry
23. Sprah L, Dernovsek MZ, Wahlbeck K, et al. Psychiatric readmissions and their association with physical comorbidity: a systematic literature review. BMC Psychiatry