Journal of Addictive Diseases, 30:110–115, 2011 Copyright c Taylor & Francis Group, LLC ISSN: 1055-0887 print / 1545-0848 online DOI: 10.1080/10550887.2011.554778

Ingestions of Hydrocodone, Carisoprodol, and Alprazolam in Combination Reported to Texas Poison Centers
Mathias B. Forrester, BS

ABSTRACT. The combination of hydrocodone, carisoprodol, and alprazolam is subject to abuse. Ingestions of this drug combination reported to Texas poison centers during 1998–2009 were identified (totaling 1,295 cases) and the distribution of ingestions by selected factors was determined. The number of cases increased from 0 in 1998 to 200 in 2007, and then decreased to 132 in 2009. The counties in eastern and southeastern Texas accounted for 80.9% of the cases. Of the patients, 57.3% were women and 94.6% were age 20 or older. Suspected attempted suicide accounted for 59.3% of the cases and intentional misuse or abuse for 27.3%. KEYWORDS. Alprazolam, carisoprodol, hydrocodone, poison center

INTRODUCTION
Abuse of prescription drugs is increasing in the United States. Rates of overdose deaths involving prescription drugs increased during 1999–2006.1 Emergency department visits involving the nonmedical use of opioid analgesics increased during 2004–2008.2 There has also been an increase in prescription drug abuse among adolescents.3,4 Hydrocodone is a prescription narcotic pain reliever sold alone or in combination with other medications known by the brand names Vicodin (Abbot Laboratories, North Chicago, IL), Lorcet (Forest Pharmaceuticals, St. Louis, MO), Lortab (Mallinckrodt Inc., Hobart, NY), and Norco (Watson Pharmaceuticals, Corona, CA). Carisoprodol is a prescription muscle relaxant

known by the brand name Soma (Meda Pharmaceuticals, Inc., Somerset, NJ). Alprazolam is a prescription anti-anxiety medication known by the brand name Xanax (Pfizer, Inc., New York, NY).5,6 Taking these three drugs in combination is not usually medically justified.6 When taken together, these medications may give users a feeling of euphoria similar to heroin.5,7 As a result, this prescription drug combination, which may be referred to by such slang terms as “Houston Cocktail,” “Holy Trinity,” or “Trio,” is subject to abuse and has resulted in deaths.5−7 All three of these medications are often dispensed at pain management clinics, some of which have dubious prescribing practices.5 The city of Houston, Texas, has been reported to have become a national sales hub and regional distribution center for the drug combination.6,7

Mathias B. Forrester is affiliated with the Texas Department of State Health Services, Austin, TX. Address correspondence to: Mathias B. Forrester, BS, Environmental Epidemiology and Disease Registries Section, Texas Department of State Health Services, 1100 W 49th Street, Austin, TX 78756 (E-mail: mathias.forrester@dshs.state.tx.us). Funding for this research was provided by a contract with the Commission on State Emergency Communications in Texas. The author would like to thank the staff of the six poison control centers of the Texas Poison Center Network (Central Texas Poison Center, North Texas Poison Center, Texas Panhandle Poison Center, South Texas Poison Center, Southeast Texas Poison Center, West Texas Regional Poison Center) who collected the data.

Mathias B. Forrester

111

According to the Texas Department of Public Safety Prescription Program, more than 144,000 prescriptions for the drug combination were dispensed in Texas in 2009, 70% of which came from Harris County, where Houston is located.6 Review of the literature failed to find published data on ingestions of this drug combination. The intent of this investigation was to describe the pattern of ingestions of this drug combination reported to Texas poison centers.

METHOD
This retrospective study used data from the Texas Poison Center Network (TPCN), a statewide poison center system comprised of six poison centers that service the entire state. Texas poison centers receive calls from the public, health care providers, and law enforcement on how to manage potentially adverse exposures and for information requests. These calls cover a variety of substances, such as medications, illicit drugs, home and industrial chemicals, plants, animals, and food. All of the Texas poison centers use a single electronic database to collect demographic and clinical information in a consistent manner. The data field definitions and allowable variables are defined by the American Association of Poison Control Centers. Cases were all ingestions reported to the TPCN during 1998–2009 that included hydrocodone, carisoprodol, and alprazolam. Multiple-drug formulations that included the medications of interest were eligible for inclusion. For example, Vicodin contains acetaminophen in addition to hydrocodone and would be eligible for the study. Ingestions involving just one or two of the medications of interest were excluded from the investigation; an ingestion must involve all three of the medications. The distribution of cases was calculated for year, caller county, patient gender and age, circumstances of or reason for the ingestion, exposure site, presence of coingestants, management site, final medical outcome, and most commonly reported adverse clinical effects. Because the presence of coingestants might affect the management and outcome of a patient, management

site, final medical outcome, and most commonly reported adverse clinical effects were evaluated for total cases and those cases not involving coingestants. The caller county is the county from which the call originated. If the call originated from a health care facility, then the caller county was recorded as the county where the health care facility was located and not necessarily where the patient resided. Texas poison center agents often do not collect information on the patient’s residence if it differs from the caller’s location. The final medical outcome is assigned by the agent managing the case and is based on the known or expected adverse clinical effects. Medical outcome is classified according to the following criteria: no effect (no symptoms due to exposure), minor effect (some minimally troublesome symptoms), moderate effect (more pronounced, prolonged symptoms), major effect (symptoms that are life threatening or cause significant disability or disfigurement), and death. A portion of exposures cannot be followed to a final medical outcome because of resource constraints or the inability to find subsequent information on the patient. The Texas Department of State Health Services institutional review board considers this investigation exempt from ethical review.

TABLE 1. Number of Ingestions of Hydrocodone, Carisoprodol, and Alprazolam in Combination Reported to the Texas Poison Center Network During 1998–2009
Year 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Number 0 0 47 70 76 105 160 168 187 200 150 132

112

JOURNAL OF ADDICTIVE DISEASES

FIGURE 1. Ingestions of hydrocodone, carisoprodol, and alprazolam in combination reported to the Texas Poison Center Network during 1998–2009 by caller county.

Number of cases 60-434 38-59 15-37 6-14 1-5 0 Houston (Harris County)

RESULTS
A total of 1,295 ingestions of the drug combination were reported to the TPCN during 1998–2009. This represented 3.9% of the 33,365 hydrocodone, 9.3% of the 13,946 carisoprodol, and 4.7% of the 27,598 alprazolam ingestions reported to the TPCN during this time period. Table 1 presents the annual number of ingestions. No ingestions were reported in 1998 or 1999. The number of ingestions increased each year during 2000–2007 then decreased during the following 2 years. The caller county was known in 1,289 of the ingestions. Figure 1 shows the number of cases by caller county. Harris County accounted for 434 (33.7%) of the cases. Texas Public Health Regions 5 and 6, the counties in eastern and southeastern Texas, accounted for 1,043 (80.9%) of the cases.

The distribution of cases by patient gender was 742 (57.3%) female, 548 (42.3%) male, and 5 (0.4%) unknown. Sixty-three (4.9%) of the patients were aged 0 to 19, 1,225 (94.6%) were age 20 and older, and 7 (0.5%) were of unknown age. Of those adult patients with a known age, the mean age was 37 years (range: 20 to 79 years). The distribution of ingestions by the circumstances of the ingestion were 768 (59.3%) suspected attempted suicide, 354 (27.3%) intentional misuse or abuse, and 173 (13.4%) other and unknown circumstances. The exposure site was 1,171 (90.4%) in the patient’s own residence, 38 (2.9%) in a public area, 15 (1.2%) in another residence, 4 (0.3%) in the workplace, 4 (0.3%) in a health care facility, 3 (0.2%) in a restaurant or food service facility, 2 (0.2%) in a school, 13 (1.0%) in an unspecified other site, and 45 (3.5%) in an unknown site.

Mathias B. Forrester

113

Substances other than products containing hydrocodone, carisoprodol, or alprazolam were reported in 484 (37.4%) ingestions. The most frequently reported other substances were alcohol (n = 118), diazepam (n = 35), cocaine (n = 33), zolpidem (n = 29), quetiapine (n = 25), oxycodone (n = 21), marijuana (n = 20), and trazodone (n = 20). Table 2 contains the distribution of cases by management site, final medical outcome, and most frequently reported adverse clinical effects. The majority of patients was already at or en route to a health care facility when the poison center was contacted. A small number of patients were managed on site (e.g., at home). Few patients were known or expected to have no effects. The most commonly reported adverse clinical effects affected the neurological, cardiovascular, and respiratory systems. The distribution of cases with and without coingestants was similar.

DISCUSSION
This investigation examined the pattern of ingestions of a combination of hydrocodone, carisoprodol, and alprazolam reported to Texas poison centers. There is little published information on the demographics and outcome of ingestions of this drug combination. Abuse of this drug combination appears to be a particular problem in Texas. Reporting of exposures to the TPCN is generally voluntary. However, in 1999 the 76th Texas Legislature passed Texas Health and Safety Code 161.042, which requires physicians to report overdoses of controlled substances in Penalty Group 1 of the Texas Controlled Substances Act to the Texas Department of State Health Services. It was decided that this reporting would occur via the TPCN. According to Texas Health and Safety Code 481.102,

TABLE 2. Ingestions of Hydrocodone, Carisoprodol, and Alprazolam in Combination Reported to the Texas Poison Center Network During 1998–2009 by Selected Variables
All Cases Variable Management site Already at/en route to health care facility Referred to health care facility On site Unknown Final medical outcome No effect Minor effect Moderate effect Major effect Death Not followed - minimal effects expected Not followed - potentially toxic Unrelated effect Most common reported clinical effects Drowsiness Slurred speech Tachycardia Coma Respiratory depression Confusion Agitation Hypotension Hypertension Ataxia Total Number % Cases Without Other Coingestants Number %

1,213 68 12 2 109 550 313 146 9 20 144 4 845 271 179 168 113 111 79 70 66 58 1,295

93.7 5.3 0.9 0.2 8.4 42.5 24.2 11.3 0.7 1.5 11.1 0.3 65.3 20.9 13.8 13.0 8.7 8.6 6.1 5.4 5.1 4.5

767 40 3 1 68 355 188 84 8 14 93 1 531 169 98 97 69 67 39 43 31 31 811

94.6 4.9 0.4 0.1 8.4 43.8 23.2 10.4 1.0 1.7 11.5 0.1 65.5 20.8 12.1 12.0 8.5 8.3 4.8 5.3 3.8 3.8

114

JOURNAL OF ADDICTIVE DISEASES

hydrocodone is in Penalty Group 1, although carisoprodol and alprazolam are not. It is not known how thoroughly physicians comply with Texas Health and Safety Code 161.042. Variations in compliance might bias the results of the study. No ingestions of the drug combination were reported to TPCN prior to 2000. Afterward, the number of reported ingestions increased each year through 2007 then decreased in 2008 and 2009. One potential explanation for the recent decline is that a new Texas monitoring requirement went into effect in 2008. According to this requirement, pharmacies now reported all prescriptions that physicians wrote for these controlled substances. Investigators used these records to examine pain management clinics to identify individuals who were writing large numbers of prescriptions for the drug combination, and prosecutions of physicians occurred.5 Eighty-one percent of the ingestions were reported in eastern and southeast Texas, and the county with the highest number of ingestions was Harris County, where Houston is located. This is consistent with reports that Houston has become a national sales hub and regional distribution center for the drug combination.6,7 This suggests that TPCN data may be useful for tracking where prescription drug abuse is occurring in the state. Eighty-seven percent of the ingestions were reported to have occurred as a result of suspected attempted suicide or intentional misuse or abuse with 13% due to other reasons. That the majority of the ingestions were for nonmedical purposes might be expected considering that the particular combination of medications is usually medically unjustified.6 The majority of the ingestions were known or expected to involve at least minor clinical effects. In addition, few patients were managed on site (e.g., at home), with most of the patients already at or en route to a health care facility when the poison center was contacted. Because the drug combination usually is associated with some form of abuse, individuals might be reluctant to contact poison centers about potentially adverse ingestions. As a result, most of the ingestions might be expected to be reported by

health care facilities, which are primarily likely to see ingestions when the patient is experiencing some adverse effect to the drug combinations. Exposures to the illicit drugs cocaine, heroin, and marijuana that were reported to Texas poison centers exhibit a similar pattern with respect to management site and final medical outcome.8 The most frequently reported adverse clinical effects were neurological (drowsiness, slurred speech, coma, confusion, agitation, ataxia), cardiovascular (tachycardia, hypotension, hypertension), and respiratory (respiratory depression). These particular clinical effects have been reported with the individual drugs in the combination, with some of the same effects reported with more than one of the medications.9 Ingestions of hydrocodone, carisoprodol, and alprazolam in combination reported to Texas poison centers have been increasing until the past few years. The majority of ingestions were reported from eastern and southeastern Texas, with the highest number of ingestions reported from Harris County. Most of the patients were female, adult, and managed at a health care facility and their use of the combination of drugs resulted in some sort of adverse clinical effects, particularly neurological, cardiovascular, or respiratory.

REFERENCES
1. Warner M, Chen LJ, Makuc DM. Increase in fatal poisonings involving opioid analgesics in the United States, 1999–2006. NCHS data brief, no 22. Hyattsville, MD: National Center for Health Statistics; 2009. 2. Centers for Disease Control and Prevention. Emergency department visits involving nonmedical use of selected prescription drugs: United States, 2004–2008. MMWR Morb Mortal Wkly Rep 2010; 59:705–9. 3. Setlik J, Bond GR, Ho M. Adolescent prescription ADHD medication abuse is rising along with prescriptions for these medications. Pediatrics 2009; 124:875–80. 4. Fadel S. Prescription drug abuse on rise for teens. Fort Worth StarTelegram. November 26, 2004. 5. Horswell C. Harris County a hot spot for potent drug trio. Houston Chronicle. May 31, 2010. Available from: http://www.chron.com/disp/story.mpl/ metropolitan/7029413.html.

Mathias B. Forrester

115

6. Olsen L. The other drug war. Houston Chronicle. July 19, 2010. Available from: http://www.chron.com/ disp/story.mpl/headline/metro/7114116.html. 7. Horswell C. Drug scam may lead to a view that has bars. Houston Chronicle. July 5, 2010. Available from: http://www.chron.com/disp/story.mpl/metropolitan /7095170.html.

8. Forrester MB. Impact of legislation on illicit substance surveillance by poison centers in Texas. J Registry Management 2005; 32:118–23. 9. Olson KR, editor. Poisoning & drug overdose, 5th ed. New York: The McGraw-Hill Companies; 2007.