A warehouse worker falls from a forklift and sustains a traumatic brain injury (TBI). In the emergency department, he receives pain medication for his headaches. The hospital prescribes an antiepileptic for seizure prophylaxis. A psychiatrist adds an antidepressant for post-injury mood changes. His primary care physician prescribes a sleep aid for insomnia. The neurologist adds a different medication for persistent headaches.
Six months later, this injured worker is taking seven different medications and struggling with fatigue, cognitive fog, and difficulty returning to work. The medications treating his TBI symptoms may now be creating new barriers to recovery.
This is the polypharmacy trap in traumatic brain injury management, and it’s more common than most workers’ compensation stakeholders realize.
The Scope of the Problem
Research shows that 45-85% of TBI patients are prescribed psychotropic and pain medications following their injury.1 A recent population-based study found that TBI patients were nearly twice as likely to experience polypharmacy, defined as using five or more different medication classes simultaneously, compared to matched controls.2
In workers’ compensation, these statistics translate to complex claims with escalating pharmacy costs, prolonged disability, and recovery hindered by the very treatments intended to help.
The challenge stems from TBI’s wide-ranging effects. Brain injury doesn’t present as a single problem requiring a single solution. Instead, injured workers may experience headaches, sleep disturbances, mood changes, cognitive difficulties, behavioral dysregulation and pain from associated injuries, each potentially prompting a separate prescription.3
How TBI Leads to Polypharmacy
The path to polypharmacy in TBI claims typically follows a predictable pattern:
Acute Phase (Emergency/Hospital): Antiepileptics for seizure prophylaxis, opioids for pain, antiemetics for nausea, medications for intracranial pressure management
Subacute Phase (Weeks 1-4): Continuation of acute medications, addition of sleep aids, antidepressants for emerging mood symptoms, stimulants for cognitive function
Chronic Phase (Beyond One Month): Persistent medications from earlier phases, plus treatments for headaches, anxiety, vestibular symptoms, and any concurrent injuries4
Each specialist encounter may add another medication. The emergency physician, neurologist, psychiatrist, pain management specialist, and primary care provider each address their domain rarely with comprehensive awareness of the complete medication regimen.
The Recovery Paradox
Here’s where medication management becomes critical for workers’ compensation outcomes: many medications prescribed to treat TBI symptoms can actually impair the recovery they’re meant to support.
Sedating medications, including antipsychotics and opioids, cloud cognition and slow rehabilitation progress. Benzodiazepines warrant particular caution: they are generally discouraged in TBI recovery due to their potential to interfere with neuroplasticity, worsen balance and increase fall risk, compounding the deficits the injured worker is working to overcome.5 An injured worker already struggling with impaired attention, memory, and processing speed doesn’t benefit from additional cognitive suppression.
Antiepileptics are not indicated for mild TBI; however, in moderate‑to‑severe TBI, these medications are used for early post‑traumatic seizure prevention, but guidelines recommend discontinuation after seven days in patients without a seizure history. 6 Despite this, continuation is common. These medications carry significant side effects including cognitive slowing and drug interactions.
Multiple antidepressants may be layered as symptoms persist, despite limited evidence for combining agents and significant potential for adverse effects when multiple psychotropic medications interact.
The cumulative effect: medications create a sedated, cognitively impaired state that delays return-to-work. Critically, medication side effects, especially with polypharmacy, may be misattributed to permanent brain injury severity, complicating impairment assessment and prolonging disability determination long after the underlying injury has stabilized.
Appropriate Medication Use in TBI
This doesn’t mean TBI patients shouldn’t receive pharmacological treatment. Many medications serve important roles:
Antidepressants (particularly SSRIs like sertraline) show evidence for treating post-TBI depression and may support cognitive recovery.7
Stimulants (methylphenidate, amantadine) demonstrate benefit for attention, processing speed, and arousal in select patients. Importantly, amantadine and other neurostimulants should be used on an individualized basis. Their benefits in appropriately selected patients are real, but broad or reflexive prescribing is not supported by evidence.8
Targeted headache treatment addresses one of the most common and disabling consequences of a TBI.
Sleep medications (when used judiciously and short-term) can address the sleep disruption that perpetuates other symptoms.
The key is strategic, evidence-based prescribing rather than reflexive symptom-chasing with multiple agents.
Red Flags for Claims Management
In partnership with your pharmacy benefit manager, workers’ compensation teams should be alert to:
- Antiepileptics beyond 7 days in patients without documented seizures
- Multiple sedating medications used concurrently (opioid + benzodiazepine + antipsychotic)
- Indefinite continuation of medications prescribed acutely without reassessment
- Concurrent prescribing from multiple providers without coordination
- Lack of medication trials adding new agents without discontinuing ineffective ones
Practical Intervention Strategies
- Medication Reconciliation at Transition Points When TBI patients move from hospital to outpatient care, work with your PBM to conduct a comprehensive medication review. Which acute-phase medications still serve a purpose? Which were time-limited interventions that should be discontinued?
- Clear Therapeutic Goals Every medication should have a defined purpose and measurable outcome. “For headaches” is insufficient—specify the type, frequency, and expected improvement. If the goal isn’t met after appropriate trial, discuss discontinuation with the treating provider rather than adding another agent.
- Deprescribing Protocols Actively reduce medications as recovery progresses. Many TBI patients improve significantly in months 3-12, yet medication regimens often remain unchanged from the acute phase.
- Provider Coordination Ensure someone—ideally a primary provider or rehabilitation physician—owns the complete medication regimen. Multiple specialists should communicate rather than prescribe in isolation.
- Non-Pharmacological Alternatives Cognitive rehabilitation, vestibular therapy, sleep hygiene, psychological counseling, and gradual return to activity often address TBI symptoms more effectively than additional medications.
The Pharmacy Benefits Management Role
Your PBM can provide a level of oversight through their utilization management protocols by:
- Flagging claims with 5+ concurrent CNS-active medications for clinical review
- Questioning indefinite antiepileptic use without seizure documentation
- Monitoring for duplicative therapy (multiple agents from same class)
- Supporting deprescribing by facilitating provider communication
- Recommending specialist consultation when medication management becomes complex
A Case Study Approach
Consider the forklift operator from our opening scenario. After comprehensive medication review, his treatment team discovered:
- The antiepileptic could be discontinued (no seizures, beyond prophylaxis window)
- Two of his three headache medications were duplicative
- The sleep aid was creating morning grogginess affecting cognition
- The antidepressant was appropriate and should continue
Reducing from seven to three medications, his cognitive function improved markedly. Within six weeks, he successfully returned to modified duty.
The pharmacy savings were modest, approximately $300 monthly, but the claim outcome transformed: faster return-to-work, avoided permanent disability and preserved earning capacity. That’s where thoughtful medication management creates value.
The Bottom Line
Traumatic brain injury is complex, and affected workers genuinely need medical support. But more medications do not necessarily equal better recovery. Often, they create new obstacles.
Workers’ compensation stakeholders, from adjusters to pharmacy managers to medical directors, should view TBI medication management as an active intervention, not passive prescription approval. The goal isn’t restricting appropriate treatment; it’s ensuring that every medication serves recovery rather than hindering it.
Because the injured worker taking seven medications and unable to return to work may not need more treatment. They may need better medication management and someone willing to ask whether each prescription is still serving its purpose.
1 Frontiers in Neurology. Medication utilization in traumatic brain injury patients. 2024;15:1339290.
2 Frontiers in Neurology. Medication utilization in traumatic brain injury patients—insights from a population-based matched cohort study. 2024.
3 BC Medical Journal. Pharmacological interventions for traumatic brain injury. December 2019.
4 Centre for Neuro Skills. Polypharmacy in Traumatic Brain Injury. August 2025.
5 Psychiatric Times. Best Practices for Polypharmacy in Traumatic Brain Injury. January 2025.
6 Brain Trauma Foundation. Guidelines for the Management of Severe Traumatic Brain Injury, 4th Edition.
7 BC Medical Journal. Pharmacological interventions for traumatic brain injury. December 2019.
8 BC Medical Journal. Pharmacological interventions for traumatic brain injury. December 2019.