Pharmacogenomics Explains Unusual Prescribing: A Clinical Pearl for PI Attorneys

Amar Lunagaria — Co-Founder & Chief Pharmacist, LienScripts | March 4, 2026 | 8 min read

When defense counsel attacks a plaintiff's medication regimen as unusual or excessive, pharmacogenomic variation may explain why standard drugs failed and alternatives were necessary. Learn how genetic differences in drug metabolism justify non-standard prescribing in personal injury cases.

Pharmacogenomics -- the study of how genetic variation affects a patient's response to medications -- explains why some personal injury plaintiffs require non-standard drug regimens that defense counsel may characterize as excessive, unusual, or unnecessary. When a plaintiff metabolizes a standard medication too quickly to achieve therapeutic benefit, or too slowly and experiences severe side effects, the prescriber must deviate from textbook prescribing. That deviation is not excessive prescribing -- it is precision medicine, and attorneys who understand this science can dismantle defense attacks on their client's medication regimen.

• Pharmacogenomics explains why some patients do not respond to standard medications or experience severe side effects at normal doses
• Genetic variation in drug-metabolizing enzymes (primarily CYP450 family) causes some patients to be ultra-rapid metabolizers (medication clears too fast to work) or poor metabolizers (medication accumulates and causes toxicity)
• LienScripts tracks every medication dispensed and generates a MERIT (Medication Evaluation & Rationale for Injury Treatment) report that can contextualize medication changes within a pharmacogenomic framework
• Defense attacks on "unusual" prescribing patterns collapse when the clinical explanation is genetic variation, not prescriber error or plaintiff exaggeration
• Pharmacogenomic evidence transforms a perceived weakness (non-standard regimen) into a strength (documented treatment complexity)

The Science: Why One Size Does Not Fit All

The human body processes medications through enzyme systems, primarily the cytochrome P450 (CYP450) family. Genetic variations in these enzymes create four metabolizer phenotypes:

Normal metabolizers -- process medications at the expected rate. Standard doses produce standard effects. Most prescribing guidelines are written for this population.

Poor metabolizers -- process medications slowly. Standard doses accumulate to higher-than-expected blood levels, causing increased side effects or toxicity. These patients often need lower doses or alternative medications that use different metabolic pathways.

Intermediate metabolizers -- process medications somewhat slowly. They may experience more side effects than normal metabolizers at standard doses and may require dose adjustments.

Ultra-rapid metabolizers -- process medications so quickly that standard doses are cleared before achieving therapeutic effect. These patients may appear to be "not responding" to treatment when in reality the medication is being eliminated before it can work. They often need higher doses or alternative medications.

As Amar Lunagaria, PharmD, LienScripts' Chief Pharmacist explains, "When I review a case and see a plaintiff who cycled through three or four medications in the same class before finding one that worked, or who required a dose significantly above the typical range, my first thought is not that the prescriber was being reckless. My first thought is that the patient likely has a pharmacogenomic variation that explains the treatment course. The prescriber was responding to clinical reality, not prescribing blindly."

How Pharmacogenomics Affects PI Medication Regimens

The CYP2D6 Example

CYP2D6 is one of the most clinically significant drug-metabolizing enzymes. It metabolizes approximately 25% of all commonly prescribed medications, including many drugs used in personal injury treatment:

• Tramadol -- a prodrug that CYP2D6 converts to its active metabolite. Ultra-rapid metabolizers convert tramadol too quickly, risking toxicity. Poor metabolizers cannot convert tramadol effectively, getting minimal pain relief at standard doses.
• Codeine -- similarly a prodrug activated by CYP2D6. Poor metabolizers get almost no analgesic effect from codeine.
• Cyclobenzaprine -- metabolized by CYP2D6. Poor metabolizers may experience excessive sedation at standard doses.
• Amitriptyline and nortriptyline -- tricyclic antidepressants used for neuropathic pain, metabolized by CYP2D6.

When a plaintiff is a CYP2D6 poor metabolizer and does not respond to codeine, the prescriber must switch to an alternative analgesic that does not rely on CYP2D6 activation. This switch is not evidence of drug-seeking or treatment failure -- it is pharmacogenomically appropriate prescribing.

The CYP2C19 Example

CYP2C19 metabolizes several medications relevant to personal injury treatment:

• Diazepam and clobazam -- benzodiazepines sometimes used for acute muscle spasm
• Citalopram and escitalopram -- SSRIs prescribed for post-traumatic anxiety or depression
• Omeprazole -- a proton pump inhibitor used to manage GI side effects from NSAIDs

Poor CYP2C19 metabolizers may experience excessive sedation from benzodiazepines or excessive drug levels from SSRIs, requiring dose reductions or alternative medications.

Rebutting Defense Attacks on Prescribing

"The plaintiff's medication regimen is excessive."

Rebuttal: The regimen reflects the prescriber's response to the plaintiff's individual pharmacology. Genetic variation in drug-metabolizing enzymes means that standard single-agent therapy may be ineffective for this patient. The prescriber tried standard approaches, they failed, and the current regimen represents the clinically necessary solution for this individual. The pharmacy record documents the sequential medication switches that led to the current regimen.

"The prescriber should have used a simpler treatment plan."

Rebuttal: The prescriber likely started with a simpler plan and escalated when it proved inadequate -- a pattern documented in the pharmacy fill history. The topical-to-systemic progression, the dose escalations, and the medication switches all reflect a prescriber who followed standard clinical practice: start simple, escalate as needed. The current regimen is not the starting point -- it is the endpoint of a documented treatment course.

"The plaintiff is taking unusually high doses."

Rebuttal: Dose requirements vary based on pharmacogenomic profile. An ultra-rapid metabolizer may require doses above the typical range to achieve therapeutic blood levels that a normal metabolizer achieves at standard doses. Higher-than-usual dosing in the context of documented treatment failure at lower doses is clinically appropriate, not excessive.

"The medication changes suggest the plaintiff is doctor-shopping."

Rebuttal: Medication changes are the hallmark of a prescriber who is actively managing a patient's condition. Each change represents a clinical decision to try a different approach when the prior approach was inadequate. The pharmacy record shows these changes occurring under the same prescriber or a coordinated prescriber transition -- not the multiple unrelated prescriber pattern that characterizes doctor-shopping. LienScripts' dispensing records and the MERIT report document the continuity of care across prescriber changes.

Presenting Pharmacogenomic Context in Demand Packages

You do not need pharmacogenomic testing results to invoke this defense. The clinical evidence of medication switches, treatment failures, and dose adjustments speaks for itself. Present it as follows:

1. Document the treatment course using pharmacy fill records: initial medication, date of switch, replacement medication, date of next switch, and so on
2. Note that the sequential trial-and-failure pattern is consistent with pharmacogenomic variation in drug metabolism, a well-established clinical phenomenon
3. Explain that each switch represents the prescriber's clinical response to inadequate efficacy or intolerable side effects at the prior medication or dose
4. Conclude that the current regimen is the clinically necessary result of an individualized treatment approach, not excessive or unusual prescribing

If pharmacogenomic testing was actually performed, include the results. CYP450 genotyping is increasingly common and provides definitive evidence of metabolizer status.

The Strategic Value

Pharmacogenomic context transforms a perceived weakness into a strength. What defense counsel frames as "unusual" or "excessive" prescribing becomes evidence of treatment complexity, injury severity, and individualized medical necessity. A plaintiff whose genetic makeup requires a non-standard medication regimen has suffered a more complex, harder-to-treat injury than a plaintiff who responded to first-line therapy -- and that complexity supports higher damages.

LienScripts generates a MERIT (Medication Evaluation & Rationale for Injury Treatment) report for every case, providing pharmacist-signed documentation for demand packages that contextualizes medication changes and non-standard regimens within the clinical framework of individual patient response.

Related Resources

• Medication Switches Prove Treatment Failure -- Using therapy changes as severity evidence
• Off-Label Prescribing and Treatment Complexity -- Explaining non-standard drug uses
• What Is a MERIT Report? -- Understanding the pharmacist-authored clinical summary