Polypharmacy rarely announces itself. It accumulates one reasonable prescription at a time, and when a claims professional pulls the injured employee’s full medication list, no single line item looks like a problem on its own.
Polypharmacy, broadly defined, is the concurrent use of multiple medications by a single patient, typically five or more once a claim is underway. Not all polypharmacy carries equal risk. General polypharmacy simply describes a higher medication count, and plenty of regimens at that count are appropriate and well managed. High-risk polypharmacy is a narrower and more clinically significant concept: combinations whose pharmacologic effects interact or accumulate, particularly among central nervous system (CNS) depressants such as opioids, benzodiazepines, muscle relaxants, and sedative-hypnotics. The medication count is a starting point. The combination, and how those drugs interact, is what drives the level of concern.
Consider an injured worker who is already taking daily medications for blood pressure and anxiety before a workplace injury occurs. That starting point is common, not unusual: among adults aged 45 to 64, 67.1% report taking at least one prescription drug in any given month, and 18.0% are already taking five or more.1 After the injury, the medication list can grow quickly. A soft-tissue strain may bring a muscle relaxant. Persistent nerve pain may add gabapentin. Disrupted sleep may introduce a sedative. An opioid may appear somewhere in that sequence, or it may not; many regimens reach three, four, or five concurrent medications without one. The concern is not which drug class appears first. It is the pattern that follows: how many medications accumulate, how quickly the regimen expands, and whether anyone is looking at the full medication picture instead of reviewing each prescription in isolation.
In a workers’ compensation context, it usually means a combination of analgesics, muscle relaxants, gabapentinoids, sedative-hypnotics, and psychotropics prescribed to manage pain, sleep, and mood in the aftermath of an injury, often layered on top of a regimen an injured worker may already be taking for unrelated chronic conditions, which for a meaningful share of workers already meets the five-medication threshold on its own.
Polypharmacy Doesn’t Just Slow Recovery. It Multiplies Everything Downstream.
Polypharmacy is associated with claim costs, but the more immediate concern is its effect on care, function, and return to work. The clinical risk appears well before a claim reaches six figures. When sedating medications are stacked, whether the combination includes an opioid, benzodiazepine, muscle relaxant, or gabapentinoid, the burden extends beyond overdose risk. Cognition can slow, coordination can decline, and energy can drop. The injured worker may be less able to attend physical therapy consistently or participate fully once there. Better pain control does not necessarily mean faster recovery; when oversedation limits movement and engagement, function can stall, deconditioning can set in, and an injury expected to resolve in weeks can stretch into months.
Much of the strongest claims research focuses on opioid-involved combinations, but the broader concern is not limited to opioids. The same underlying mechanism, cumulative central nervous system (CNS) burden and unmonitored drug interactions, can affect recovery even when an opioid never appears in the regimen. Viewed through that lens, the cost data below reflects the same clinical pattern from another angle.
A cohort study out of Johns Hopkins and the Louisiana Workers’ Compensation Corporation followed 11,394 lost-time claims for seven years post-injury. Benzodiazepines, the researchers found, were almost never prescribed on their own; they showed up layered on top of an opioid regimen in most cases. After controlling for attorney involvement, marital status, and diagnosis, the odds of a claim reaching $100,000 or more were 2.74 times higher with benzodiazepine use alone, 4.69 times higher when combined with a short-acting opioid, and 14.24 times higher when combined with a long-acting opioid.2
Translate that into practice and the message is simple: a benzodiazepine showing up next to a long-acting opioid on a medication list isn’t a footnote, it’s a signal to review the claim with a clinician while also increasing reserves.
A related analysis from the same research group looked at the broader psychotropic category, not just benzodiazepines, against claims from the same Louisiana cohort. Sedative-hypnotics carried an odds ratio of 2.8 for a $100,000+ claim, antipsychotics 2.6, antidepressants 2.9, and long-acting opioids alone 8.6, all independent of each other.3 The pattern holds across drug classes: the more central-nervous-system-active medications stacked into a regimen, the higher the claim cost trend, and that trend appears early. These first-year and second-year prescribing patterns are associated with outcomes that play out over the life of the claim.
An updated analysis of the same Johns Hopkins and Louisiana Workers’ Compensation Corporation cohort, expanded and followed for ten years post-injury, found that gabapentin, antipsychotics, antidepressants, and sedatives used in the first three months after injury were each independently associated with a higher likelihood of a claim reaching $100,000 or more, regardless of whether an opioid was ever part of the regimen.4
The takeaway is not any one odds ratio. It is the speed at which risk compounds. When CNS-active medications begin stacking early in a claim, the cost trajectory is often visible in the pharmacy data long before it appears in the reserve.
The Litigation Connection Is Not Coincidental
Litigation isn’t just a cost factor, it’s often a signal that an injured worker’s recovery has gone off track. Here’s where the cascade tightens. Prolonged, complex, medication-heavy claims are exactly the claims that attract plaintiff’s attorneys, and attorney involvement is associated with some of the strongest cost increases in the entire system. WCRI’s 2024 research found that attorney involvement is associated with a 284% increase in lost-time days by and a 200% increase in expense payments.5
The relationship moves in both directions. Claims that drag on are more likely to invite attorney involvement, and once representation enters the picture, the claim often becomes harder to resolve. Bernacki and Tao’s foundational 2008 study linked legal representation directly to longer claim duration and higher cost.6 For an injured worker who is not improving and is taking an escalating, multi-drug regimen, outside advocacy can begin to feel necessary. Once that happens, treatment decisions slow, independent medical exams may be contested, and the claims professional has fewer opportunities to redirect care. Long-acting opioid use alone has been associated with temporary disability duration more than three times that of claims without opioids.5 When benzodiazepines, sedatives, or multiple psychotropics are added to that picture, the delayed-recovery signal becomes even stronger.
For claims professionals, the practical point is straightforward: a growing medication list can be an early warning sign that a claim is moving toward representation, sometimes before the injured worker calls an attorney. If the prescribing pattern is addressed while it is still a clinical conversation, the claims team may still have a meaningful opportunity to support recovery, clarify the treatment plan, and reduce the likelihood of litigation.
And Yes, There Is a Mortality Risk
A study by NIOSH and West Virginia University followed 14,218 injured workers with workers’ compensation low-back injury claims through 2015. The median age at injury was just 37.7, which makes the findings especially important: the higher mortality risk was tied less to age than to how long disability lasted. Injured workers with lost work time had more than twice the expected rate of death from accidental poisoning compared with the general population. Those with permanent disability had nearly three times the expected rate, and opioids were involved in the large majority of those deaths.7 The point is not that mortality risk tells the whole story. It does not. But it reinforces the broader pattern: the same prescribing and recovery signals that raise safety concerns are also linked to delayed recovery, higher costs, and litigation risk. Interventions that shorten disability duration, improve medication oversight, or redirect care earlier are also likely to support better outcomes.
Where the PBM Fits In
Workers’ compensation pharmacy benefit managers (PBMs) play an important role in helping manage polypharmacy. Concurrent drug utilization review flags dangerous combinations, opioid plus benzodiazepine, opioid plus gabapentinoid, multiple CNS depressants, at the point of dispensing rather than months later when a claim file review surfaces the pattern. Morphine equivalent dose (MED) monitoring catches escalation before it reaches the thresholds most state guidelines treat as red flags. Peer-to-peer outreach gives the treating physician a chance to explain the clinical rationale behind a regimen, or reconsider it, before it becomes entrenched. Prior authorization and formulary controls slow down the reflexive addition of a second or third drug class, forcing that same clinical conversation instead of an automatic fill. Red-flag identification around multiple prescribers or multiple pharmacies picks up on patterns a busy adjuster juggling a full caseload may not have the bandwidth to catch alone. It’s important for claims professionals to act on the red flags and pull in appropriate clinical resources to support each claim concern before it’s too late.
Where it gets murky is that workers’ compensation PBMs don’t always have the full picture. For example, your PBM partner typically doesn’t know what medications the patient is taking outside of those being processed for the claim, and they may also be missing the medical diagnosis or up to date medical files. In these cases, it’s important that the claims system provides additional clinical oversight. Appropriate use reviews should question whether a regimen still matches the diagnosis and the stage of recovery. An injured worker six weeks past an acute strain who is still filling a muscle relaxant, a gabapentinoid, and a sedative alongside an opioid should prompt a clinical conversation about whether that combination is supporting recovery or working against it.
The goal is recovery. The medication regimen should manage pain and symptoms without suppressing the function an injured worker needs to participate in therapy, maintain sleep, regulate mood, and stay active in daily life. When the clinical picture is managed in real time, reserve accuracy and reduced litigation exposure often follow. The earlier that review happens after the date of injury, the more options remain for everyone involved: the treating physician, adjuster, nurse case manager, and PBM.
What This Looks Like on a Claim File
These signals are not instructions for a claims professional to make clinical decisions. They are practical prompts to pause, look more closely, and bring in the right clinical resource while there is still time to influence the claim’s direction.
- Count the CNS-active medications, not just the opioids. A muscle relaxant, a gabapentinoid, and a sedative carry cumulative sedation burden with no opioid anywhere on the list.
- Treat a benzodiazepine sitting next to a long-acting opioid as the highest-priority combination on the list. The associated odds of a claim reaching $100,000 or more are 14.24 times higher; that warrants a clinical review and a reserve conversation in the same week.
- Watch the rate of growth, not only the count. Two additions in six weeks tells you more than a stable regimen of four.
- Ask whether the regimen still matches the diagnosis and the stage of recovery. An injured worker six weeks past an acute strain, still filling what was prescribed in week one, is a conversation trigger.
- Assume the pharmacy data is incomplete. Medications for pre-existing conditions typically fall outside the claim, and multiple prescribers or multiple pharmacies fragment the picture further; what the PBM can see is rarely the full list the injured worker is taking.
- Read a growing medication list as an early litigation indicator. The prescribing pattern often precedes the attorney call, and that gap is the window where a claims team still has options.
Polypharmacy is only one red flag on an injured worker’s path to recovery, but it is one claims teams cannot afford to overlook. Multiple medications do not always mean something is wrong; many regimens are appropriate, intentional, and well managed. But when medications begin to accumulate, the pattern deserves a closer look. The earlier the claims team and PBM review what the medication list is showing, the better positioned they are to support recovery, reduce avoidable risk, and intervene before the claim’s direction becomes harder to change.
1 National Center for Health Statistics. Health, United States, 2019: Table 39. Prescription drug use in the past 30 days, by sex, race and Hispanic origin, and age: United States, selected years 1988-1994 through 2015-2018. Hyattsville, MD: National Center for Health Statistics; 2021. https://www.cdc.gov/nchs/data/hus/2019/039-508.pdf 2 Lavin RA, Tao XG, Yuspeh L, Bernacki EJ. Impact of the combined use of benzodiazepines and opioids on workers’ compensation claim cost. J Occup Environ Med. 2014;56(9):973-978. https://pubmed.ncbi.nlm.nih.gov/25046322/ 3 Tao XG, Lavin RA, Yuspeh L, Weaver VM, Bernacki EJ. The association of the use of opioid and psychotropic medications with workers’ compensation claim costs and lost work time. J Occup Environ Med. 2015;57(2):196-201. https://pubmed.ncbi.nlm.nih.gov/25654521/ 4 Tao XG, Lavin RA, Yuspeh L, Tsourmas NF, Kalia N, Leung N, Williams L, Hunt DL, Green-McKenzie J, Bernacki EJ. Early drug prescription patterns as predictors of final workers’ compensation claim costs and closure: an updated analysis on an expanded cohort. J Occup Environ Med. 2022;64(12):1046-1052. https://pubmed.ncbi.nlm.nih.gov/35902352/ 5 WCRI data, cited in: The Current State of Complex Claims in Workers’ Compensation: Understanding the Drivers of Rising Costs and Duration. Risk & Insurance. 2025. https://riskandinsurance.com/the-current-state-of-complex-claims-in-workers-compensation-understanding-the-drivers-of-rising-costs-and-duration/ 6 Bernacki EJ, Tao XG. Attorney involvement, claim duration, and workers’ compensation costs. J Occup Environ Med. 2008;50(9):1013-1018. https://pubmed.ncbi.nlm.nih.gov/18784549/ 7 Martin CJ, Jin C, Bertke SJ, Yiin JH, Pinkerton LE. Increased overall and cause-specific mortality associated with disability among workers’ compensation claimants with low back injuries. Am J Ind Med. 2020;63(3):209-217. https://stacks.cdc.gov/view/cdc/125201/cdc_125201_DS1.pdf