A Healthesystems publication

Fall 2013

Deadly Drug Combinations Escaping Notice

This potentially deadly drug mixture may not be on every payer’s radar screen because of the relatively low AWP for each drug. But when abuse is involved, payers need to seriously consider the additional costs of the consequences of abuse of this drug combination — detoxification and rehabilitation — as well as the real potential for loss of life.

The challenge for workers’ compensation payers is to identify and monitor risky drug combinations before they endanger the injured worker or are diverted to the street.  The risks inherent in opioid therapy have been well documented and significant efforts are being made by legislators, federal agencies, PBMs, payers and others to reduce opioid use in the workers’ compensation population. But opioid use alone is not the only concern.

What is escaping the notice of many payers is a popular but dangerous drug combination of short-acting opioids, muscle relaxants and anti-anxiety drugs. The combination is called the holy trinity by drug abusers because of the feeling of euphoria that it can produce — similar to that of heroin. There is a ready street market for these drugs, making them ripe for diversion. This led Healthesystems to dub the combination the unholy holy trinity.

C.S. Schade, MD, PhD, a past president of the Texas Pain Society, said he could “conceive of no legitimate medical reason” that the three medications would be prescribed together.1 Though only a small number of claimants are prescribed this potentially deadly combination, payers should be aggressive in managing these outliers.

Identifying Problem Claims is the First Step

The challenge for PBMs and payers is to spot abusive drug behaviors before a claim spirals out of control. Opioid drug therapy is a major cost driver in workers’ compensation and is well known to pose high risks for abuse, drug diversion and accidental or intentional drug overdoses. Each component of the combination carries its own risk for abuse and addiction.

It is becoming more well-known that drug overdoses seldom involve one agent. Opioid abusers learn to predict the effect of an opioid dose and can easily overdose when they seek to augment the euphoria with alcohol and/or other medications. When they augment it with carisoprodol and benzodiazepine, the risk for overdose is raised exponentially. 

Escaping Notice

Individually, opioids, carisoprodol and benzodiazepine have low average wholesale prices (AWP), costing pennies to about $1 per tablet. However, when abuse is involved, payers need to seriously consider the additional costs of the consequences of abuse of this drug combination — detoxification and rehabilitation — as well as the real potential for loss of life.

Common Components of the Holy Trinity

Short-Acting Opioids
Vicodin®, Lortab® and Opana®
Muscle Relaxants
Carisoprodol marketed as
Anti-Anxiety Drugs
Benzodiazepines marketed as
Xanax®, Valium® and Klonopin®

Taking the Next Steps

The Healthesystems clinical and technology teams worked together to create complex system logic and edits that identify claimants who have been prescribed all three types of drugs at some point in their treatment.  The information is shared with claims professionals along with clinical guidance on best practices for achieving an optimal outcome for the injured worker.

Healthesystems recommends that payers and PBMs clearly identify claimants who have been prescribed the opioid/ carisoprodol/ benzodiazepine combination so aggressive strategies can be implemented.  This could include clinical outreach to the prescriber(s), requests for justification of medical necessity, escalation for review to a clinical professional or a combination of efforts. 

Celebrity Deaths Involving Prescription Opioids in Combination

The use of opioids in combination with alcohol and other prescription drugs was a factor or direct cause of death for several high profile actors and athletes.

  Heath Ledger
Actor, 28
Oxycodone, hydrocodone, diazepam, temazepam, alprazolam and doxylamine7
  Dana Plato
Actress, 34
Carisoprodol and hydrocodone8
  Derek Boogaard
Professional hockey player, 28
Alcohol and oxycodone11
  Edward Fatu “Umaga”
Professional wrestler, 36
Hydrocodone, carisoprodol and diazepam10
  Erica Blasberg
Professional Golfer, 25
Butalbital, temazepam, alprazolam, codeine, hydrocodone and tramadol9




1 -Horswell C, Houston Chronicle. Harris leads state in doctors doling out potent drug combo. May 31, 2010. http://www.chron.com/news/houston-texas/article/Harris-leads-state-in-doctors-doling-out-potent-1712372.php.. Accessed August 16, 2013.
2 - Lipton B, Laws C, Li L. August 2011. Workers Compensation Prescription Drug Study: 2011 Update. NCCI. https://www.ncci.com/documents/2011_ncci_research_rxdrug_study.pdf. Published September 12. 2011. Accessed August 13, 2013.
3 - Drug Enforcement Administration. Schedules of Controlled Substances: Placement of Carisoprodol into Schedule IV. http://www.deadiversion.usdoj.gov/fed_regs/rules/2011/fr1212_10.htm. Published December 12, 2011. Accessed August 20, 2013.
4 - Drug Abuse Warning Network. National Estimates of Drug-Related Emergency Department Visits, 2011.  http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#5.1. Published May 2013. Accessed August 20, 2013.
5 -Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality (formerly the Office of Applied Studies). The DAWN Report: Highlights of the 2009 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. http://www.oas.samhsa.gov/2k10/DAWN034/EDHighlights.htm. Published December 28, 2010. Accessed August 12, 2013.
6 -Policy Impact: Prescription Painkiller Overdoses. Atlanta, GA: Centers for Disease Control and Prevention; 12/19/2011. Available at: http://www.cdc.gov/homeandrecreationalsafety/rxbrief/ . Accessed August 21, 2012.
7 - Lieberman P., 6-Drug Combo Blamed, Los Angeles Times, February 8, 2008 accessed at www.latimes.com on October 30, 2013
8 -Associated Press, Doctor Rules Dan Plato’s Death Suicide, May 22, 1999, Lubbock Avalanche-Journal, accessed at www.lubbockonline.com October 2, 2013.
9 -http://www.drugs.com/celebrity_deaths.html, accessed October 2, 2013.
10 -Middleton M., Report on Edward “Umaga” Fatu’s Death, March 1, 2010, AllWrestling.com, accessed October 2, 2013.
11 -Associated Press, Derek Boogaard death ruled accidental, May 20, 2011, accessed at http://sports.espn.go.com/new-york/nhl/news/story?id=6570143 October 2, 2013.
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