Adolescent Health Care: A Practical Guide

Chapter 72

Laboratory Testing for Substances of Abuse

Sharon Levy

John R. Knight

Drug Testing in the Primary Care Clinic

Drug testing is a complicated procedure that can be controversial and contentious. When done correctly it can be a useful part of a substance use disorder assessment; however, as with any other laboratory test it is best used in conjunction with and not instead of history and physical examination findings. This chapter discusses indications for drug testing, proper specimen collection and validation techniques, interpretation of results, and follow-up.

Indications for Urine Drug Testing in the Primary Care Clinic

Drug use by teens often presents to medical attention with nonspecific signs and symptoms (such as fatigue, excessive moodiness, school failure) and urine drug testing may be a useful assessment tool when parents notice these signs, yet the teenager denies drug use. Health care providers should consider recommending a drug test if a parent has a reasonable basis for suspicion of drug use, such as decrease in school performance, loss of interest in hobbies or extracurricular activities, change in friends, lying or stealing, or is found with drug paraphernalia. However, a drug test may be unnecessary if the teenager is forthcoming regarding his/her drug use history. The health care provider presented with these concerns should interview the patient alone without the parents present at some point during the visit.

In clinical situations in which a drug test is recommended, health care providers and parents should recognize that a single negative drug test result confirms that a patient has not used drugs detectable by the screen in the past 24 to 48 hours (for most substances), but does not rule out a drug use disorder, and, a positive drug test result does not confirm a diagnosis of drug abuse or dependence (Schwartz, 1993). Therefore, although drug testing can provide useful clinical information it must always be considered within the context of the history and physical findings. Health care providers should proceed cautiously when parents request a drug test based on concerns external to the patient (many drugs available in the neighborhood or school, family history of drug problems, and so on). Most experts agree that drug tests are not a useful screening procedure for general populations as their sensitivity for detecting drug use in unselected populations is low (Hammett-Stabler et al., 2002; Schwartz, 1993).

There is little consensus among physicians regarding the indications for drug testing in adolescents and little consistency in how to proceed when a urine drug test result is positive (Levy et al., 2006). Further evidence-based studies and clinical practice guidelines are needed from health professional organizations (Irwin, 2006).

Consent/Assent

Policy guidelines from the American Academy of Pediatrics state that physicians should obtain assent from competent adolescents before ordering a drug test; parental consent alone is not sufficient (American Academy of Pediatrics, 1996). A health care provider should never order a drug test without explaining the procedure to the patient, as this may decrease trust, impair communication, and make therapeutic alliance between the patient and the health care provider difficult. If a teenager refuses a drug test that is clearly indicated, the health care provider should counsel parents to use appropriate limit setting and consequences. For example, a parent might suspend car privileges or limit socializing with friends until they are reassured that their child is not using drugs. Although drug testing may be an inconvenience to an adolescent, a series of negative drug test results may also present advantages, such as rebuilding trust between parent and child or providing evidence to schools or courts supporting abstinence from drugs.

Confidentiality/Sharing Results

Federal regulations afford information regarding drug use treatment greater confidentiality protection than other information recorded in a medical record. A health care provider should not share drug test results with anyone without the express written consent of the patient (if older than 18 years) or the parent of a minor patient. Drug test results should be omitted from general health summaries or other medical record transmittals as per Health Insurance Portability and Accountability (HIPAA) regulations.

Before ordering a drug test, the health care provider, teenager, and parent(s) should discuss who will receive results. Any patient with a positive drug test result requires

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further assessment and intervention. Some health care providers require permission to share the interpretation of the drug test result with parents whenever a drug test is ordered because adolescent patients are more likely to comply with follow-up appointments when a parent is involved. However, before sharing a positive drug test result, the health care provider should review the results with the teenager privately, as a drug test may be positive even when a teenager has not used illicit drugs. To avoid false accusation, the health care provider should conduct a private interview with the teenager before interpreting the drug test (see subsequent text).

Drug Testing of Trauma Victims in the Emergency Room Department

The Department of Health and Human Services recommends that all adult trauma patients be screened for drug and alcohol use to determine whether they may have a drug or alcohol disorder (CSAT,1995). Recent research has demonstrated that rates of drug tests positive for cannabis, alcohol, and opiates among 14- to 17-year-old trauma patients was 39% (Ehrlich, 2006). Although drug testing did not alter the acute management of these patients, testing helped to identify drug use by these teenagers and allowed referral for further assessment. On the basis of these data, drug screening should be considered in all adolescent trauma patients after obtaining informed consent. All adolescents who present to an emergency department in an unresponsive condition should have a urine drug screen as part of an evaluation for altered mental status.

Types of Drug Tests

Drugs and their metabolites can be detected in several biological matrices, including hair, saliva, breath, blood, and urine (Wolff et al., 1999).

Urine

Urine drug testing has been well studied and standardized. Urine drug concentrations are relatively high and drugs and their metabolites are excreted in the urine for a period of time after acute intoxication, making urine the preferred biological fluid for drug testing in the primary care setting.

There are two principle types of urine drug tests—immunoassays and gas chromatography/mass spectrometry (GC/MS). Immunoassays are relatively nonspecific tests that can detect a variety of drugs. Standard laboratory screening panels are done with immunoassays, as are point of service tests. Immunoassays are quite sensitive and can be used to eliminate samples from further consideration. However, these panels are relatively nonspecific and a number of cross-reacting substances can cause false-positive drug test results (Table 72.1) (Hawks and Chiang, 1986). Therefore, immunoassays are best used as a screen; all positive test results should be confirmed with a second test using a different, more specific testing method such as GC/MS. Requisitions for laboratory tests should include GC/MS confirmation for all positive test results as a separate order. Point of service tests are confirmed by sending the sample to the laboratory for GC/MS. Immunoassay screens should not be repeated for confirmation of an initial positive test result.

Hair/Breath/Saliva/Sweat

1. Hair: Although not a routine method of drug testing, hair testing can provide a longer window of detection (up to 180 days) in patients with long hair and may be useful in some settings. Current drug use can be difficult to distinguish from past use with this testing method. Marijuana use is difficult to confirm by hair testing because of slow deposition into some hair types. Because coarse hair absorbs drugs more readily, the possibility may exist of race/ethnicity inequity in hair testing for drugs (Med Lett Drugs Ther, 2002).
2. Breath tests: Breath tests are available for alcohol, and can give a reliable indication of the blood alcohol level at the time of the test (Gullberg, 2003).
3. Saliva tests: Saliva tests are also available for alcohol, and newer tests for a variety of drugs have recently entered the market. Like breath tests, drug levels in saliva reflect blood levels at the time of testing (Drummer, 2005; Verstraete, 2005). Saliva testing has not been nationally standardized and cutoff levels (the threshold level at which a drug test becomes positive) vary from product to product.
4. Sweat tests: Sweat wipes and patches that can be worn for up to 14 days are available, although they are used infrequently because of the high rate of false-positive results from external sources of drugs (Kidwell and Smith, 2001).

Practical Issues in Urine Drug Testing

Test Selection

Substance abuse panels vary and health care providers should be familiar with the panels offered by the laboratories they use. Standard multipanels include the five classes of drugs that are required in federally mandated tests—cannabis, cocaine, amphetamines, phencyclidine (PCP), and opiates (American College of Environmental and Occupational Medicine, 2003). Many laboratories include additional classes of drugs in multiscreen substance abuse panels. Of note, immunoassay screens detect drug classes such as opiates or benzodiazepines, but may not detect every drug in the class. For example, standard opiate screens may not detect synthetic opioids such as oxycodone and hydrocodone (Gourlay et al., 2002). A test for urinary ethyl glucuronide should be ordered to detect alcohol use, as this metabolite has a longer half-life (up to 5 days) and is more sensitive than tests of urinary alcohol (Skipper et al., 2004). Communication and clarification with laboratory staff can reduce interpretation errors.

Specimen Collection

Because of the multitude of methods for falsifying urines, health care providers who choose to order urine drug tests from their offices must be diligent. Most experts recommend either a directly observed urine specimen (the specimen must be directly observed as it passes

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from the urethra into the specimen container) or using the National Institute on Drug Abuse (NIDA) protocol for specimen collection, which is available online (http://www.drugfreeworkplace.com). The Department of Transportation developed this protocol in compliance with the federal mandate to test transit employees, and many commercial laboratories have the necessary facilities and trained staff for specimen collection. The protocol requires the teen (or an accompanying parent) to present photographic identification before donating the sample. The patient then empties his/her pockets, washes his/her hands, and enters a private specimen donation room with all running water shut off. A blue dye is added to the standing water in the toilet. A laboratory staff member checks the temperature of the urine immediately after donation; specimens with a temperature below 90°F or above 100°F are considered substituted or diluted.

TABLE 72.1 Drugs of Abuse, Common Urine Metabolites, Maximum Window of Detection, Molecules that May Cross-react with Screening Panels and Licit Sources of the Drug

Common Name(s) Urine Metabolite Maximum Window of Detection Included in Standard Panels Substances that Can Cross-react with ELISA Screensa Sources of Clinical False Positivesb ELISA, enzyme-linked immunosorbent assay; NIDA, National Institute on Drug Abuse; OTC, over-the-counter; NSAID, nonsteroidal anti-inflammatory drug; ADHD, attention deficit hyperactivity disorder; MDA,; a Gas chromatography/mass spectrometry (GC/MS) confirmation will be negative. b May result in positive drug test results in the absence of illicit drug use. c Vicks inhaler contains the inactive isomer l-methamphetamine, but trace amounts of the d-isomer may be present, resulting in a positive drug test result. Alcohol · Ethanol · Ethylglucuronide · 24–36 hr · 80 hr Not part of NIDA-5, but alcohol included on some standard panels · OTC cough and cold liquid medications · “Nonalcoholic” beer · Foods prepared with uncooked alcohol (such as rum cake) Marijuana, “weed” Tetrahydrocannabinol (THC) and other cannabinols Infrequent users: 3–4 d Daily users: 4–6 wk Yes · NSAIDs (ibuprofen, ketoprofen, naproxen) · Promethazine vitamin B supplements Prescription Marinol use (uncommon in teenagers) Cocaine Cocaine, benzoylecgonine 2–3 days Yes Amoxicillin Decocainized teas, commonly in use in South America Amphetamine Several members in class 2–4 days Yes · Cold medications that contain ephedrine, pseudoephedrine, propylephedrine, phenylephrine, desoxyephedrine · Phenylpropanolamine (present in OTC diet aids) Prescription use of stimulants (for ADHD or other conditions) including Adderall and Dexedrine Methamphetamine Methamphetamine, p-hydroxymethamphetamine, amphetamine 24–48 hours Yes, detected on amphetamine panel · Methamphetamine from OTC medications such as Vicks inhalerc · Prescription use of Desoxyn, benzphetamine, dimethylamphetamine, famprofazone, fencamine, furfenorex, selegiline Ecstasy, 3,4 methylenedioxymethamphetamine (MDMA) MDMA, methylenedioxyamphetamine (MDA), mono- and dihydroxy derivatives 24–48 hours No Phencyclidine (PCP), “dust” Glucuronic conjugates of 4-phenyl-4-piperidinocyclohexanol and other metabolites 8–10 days Yes Dextromethorphan Lysergic acid diethylamide (LSD), “acid” LSD, n-demethylated, deethylated, and hydroxylated metabolites 24 hours No Opiates · Codeine: norcodeine, morphine · Heroin: 6-acetylmornphine, morphine · Morphine: morphine glucuronide, normorphine 2–3 days Yes, but synthetic opioids are detected only in very high doses Fluoroquinolone antibiotics · Consumption of a large quantity of poppy seeds (poppy seeds contain trace amounts of morphine; typical poppy seed consumption produce urine metabolite concentrations under standard thresholds) · Prescription use of opiate medication for pain Benzodiazepines Oxazepam common metabolite for several, but not all, benzodiazepines Up to 2 weeks, but varies for individual drugs Not part of “NIDA 5”, but included in many standard panels Prescription use of benzodiazepines for anxiety or other conditions Inhalants Many in class <24 hours No Inhalants are largely excreted by the lungs although some metabolites may be excreted in the urine; special testing required for detection

Specimen Validation

All drug tests should be ordered with an accompanying specific gravity and urine creatinine level. A negative screen is of absolutely no clinical usefulness in the absence of evidence of adequate urine concentration. Samples with a creatinine <20 mg/dL and a specific gravity of <1.005 are too dilute for proper interpretation and should be repeated with specific instructions regarding water ingestion before specimen donation (American College of Environmental and Occupational Medicine, 2003). In general, patients should be instructed to ingest no more than 20 oz of fluid in the 3 hours preceding donation of a specimen. Although it is impossible to protect against all the possible methods of falsifying urine substances, proper specimen collection and validation significantly decrease the possibility of tampering.

TABLE 72.2 Interpretation of Negative Urine Drug Test Results

Screen Result Laboratory Interpretation Possible Clinical Interpretations Next Step Negative Substance in question not detected in the urine Substance may be either present at a concentration below the sensitivity level set for the test, or not present · Patient has not used the substance in question within the window of detection (24–48 hours for most substances) · Adulterated or substituted samples should be considered clinically positive · Patient has diluted, substituted or adulterated the urine sample causing a false-negative result · Dilute samples should be repeated; multiple dilute samples should be considered positive

Interpretation

1. Negative test results

Drug test results have both laboratory and clinical interpretations. The laboratory reading of a drug test result will be negative whenever the drugs in the test panel are not detected in the sample provided. Negative drug test results must be interpreted with caution (Table 72.2). A drug test result will be negative in the context of drug use in the following circumstances:

• The patient stopped using the substance in question within the window of detection (24–48 hours for most substances). Teens who know they will be drug tested may be able to stop long enough in advance to have a negative result.
• The patient has diluted the urine sample. Specimens with creatinine levels between 5 and 20 and specific gravity <1.005 are dilute, and should be repeated after limiting fluid ingestion immediately preceding the test. A repeated dilute specimen should be considered clinically positive.
• The patient has substituted the urine sample. Laboratory specimens with creatinine <5 should be considered substituted (not urine), and the clinical interpretation of the drug test result is positive. Samples may also be substituted with synthetic urine or urine provided by an individual who had not used drugs.
• The patient has adulterated the urine sample. Bleach, soap, acid, and other chemicals interfere with drug screens and cause false-negative test results. These substances may be detected by laboratory personnel if the sample has an unusual odor or other unusual characteristics. Tests for specific adulterants may be ordered separately (in consultation with laboratory personnel) if adulteration is suspected.
• The patient has used a drug that is not detected by the panel ordered. Synthetic opioids (such as oxycodone, hydrocodone, and hydromorphone), some benzodiazepines, inhalants, and some hallucinogens are not included on most standard drug testing panels, and the inclusion of alcohol is variable. These drugs must be ordered separately in consultation with the laboratory toxicologist if use is suspected.

2. Positive test results

The laboratory reading of a drug test result will be positive whenever a molecule in the urine specimen reacts with the test panel, and this also must be interpreted with caution (Table 72.3). A drug test result will be positive in absence of illicit drug use in the following circumstances:

• A chemical other than an illicit drug has cross-reacted with the drug test panel (Table 72.1). Confirmatory testing with GC/MS will be negative.
• The patient has consumed the drug in the context of licit use of a prescription or over-the-counter medication, or consumed in a food. A careful patient history, including review of all prescription medications, recently used over-the-counter medications and unusual food consumption may provide an explanation for the positive drug test result if the history is consistent with the result observed.

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3. Specimens positive for cannabis

Cannabis is lipid soluble and, with chronic use, significant stores can accumulate in fat tissue. Daily users of cannabis can have detectable urine cannabinoid levels for 1 to 2 months after discontinuing use (Schwartz, 1993). The absolute level of urinary cannabinoid excretion varies with urine concentration. Once use is discontinued, however, the ratio of urinary cannabinoids to urinary creatinine will fall over time, and a decreasing ratio supports a history of discontinued use even in a patient with positive urine test results.

Presenting Drug Test Results to Adolescent Patients

All patients with positive, dilute, adulterated, or substituted urine specimens should have a return appointment to interpret drug test results. Teens should be interviewed privately to determine whether an explanation other than illicit drug use might account for the laboratory findings. After the interview, the health care provider should have enough information to determine whether the drug test result is the result of illicit drug use or whether an alternative explanation is realistic.

Table 72.3 Interpretation of Positive Urine Drug Test Results

Screen Result Laboratory Interpretation Possible Clinical Interpretations Next Step GC/MS, gas chromatography/mass spectrometry. Positive Substance in the urine has reacted with the substrate in the test panel · True positive—patient has absorbed substance in question · False positive—chemical from an over-the-counter medication, prescribed medication, or food has cross-reacted with substrate in the test panel · Order GC/MS to confirm result · If GC/MS is positive, discuss with the patient to determine if licit use of prescription or over-the-counter medications, or food consumption would explain a positive test result

Some teens will acknowledge drug use when a drug test result is positive, and this may provide an opportunity to have an honest conversation. The health care provider may elicit further drug history in an attempt to clarify diagnoses. If the teenager is willing to abstain from drug use, repeat testing may be useful for monitoring and to help rebuild trust between parent and child. Some teens will deny drug use and insist that the laboratory is in error or offer another inconsistent explanation. The health care provider should avoid arguments, but remain firm in interpretation. Repeat testing and further visits may be required before the teen is ready to give an honest history.

Approach to the Patient Interview When a Drug Test is Positive

Whenever a laboratory drug test result is positive the health care provider should interview the patient privately to determine if an explanation other than illicit drug use might account for the laboratory findings. The following may serve as an interview guide for these clinical encounters:

• If the test was not done in the office, confirm the date and location, and whether there were problems at the test site.

Did you have a drug test on (date) at (location)?

Were there any problems in the lab when you were there?

• Inform the teen that you have received an unexpected drug test result.

I have the received the results of your drug test and the test was (positive/dilute/adulterated/substituted).

• For positive specimens:

Are you taking any prescription or over-the-counter medications that might account for a positive drug test result?

Did you consume any foods that might have interfered with a drug test?

Determine whether medications or foods listed would account for the positive test result observed. For example, the use of Adderall for attention-deficit hyperactivity disorder (ADHD) would account for a positive amphetamine test result, but not a positive opioid test result.

• For dilute specimens:

Was there anything unusual about that day? Can you explain why your test was so dilute?

Tell the teen that a repeat test will be required and give specific parameters for fluid ingestion (such as no more than 8 oz of fluid in the 2 hours preceding the test). If repeated tests have been dilute inform the teenager that further renal assessment may be required.

• Ask directly about drug use:

Did you use drugs or alcohol before giving a urine test?

Presenting Urine Drug Test Results to Parents

Parental involvement is an important part of intervention for many teens with substance use disorders and disclosing a teen's drug test results to parents may be therapeutically useful, particularly when a teen has not given an honest history. It is, however, important to respect the teen's burgeoning autonomy and, when possible, to protect the therapeutic alliance between the teen and the clinician.

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A few guidelines are helpful in deciding what information to share with parents.

Approach to Sharing Urine Drug Test Results with Parents

• Obtain assent or consent (as appropriate) from the teenager to share drug test results beforeordering the drug test.
• When a drug test result is positive, dilute, adulterated, or substituted always interview the patient privately to interpret drug test results before sharing information with parents.
• Discuss with the teenager exactly which information will be shared with parents. Avoid sharing details that do not impact further assessment or treatment, such as how drugs were obtained or who else used them.
• Offer the teenager the opportunity to speak with parents first (with the clinician present for support and to confirm that information was correctly conveyed).
• If the teenager has not acknowledged the drug use, discuss the teen's alternative explanation for the positive drug test result, but, explain that the explanation offered is inconsistent with laboratory results.

Negative results of drug tests done with proper collection and validation techniques provide good support for a history of no drug use, at least within the window of detection of the substances detected. Health care providers must recognize, however, that even carefully done urine tests have limitations and cannot completely rule out drug use. Parents should understand the limitations of urine drug testing. Continued monitoring by parents, repeat drug testing, or referral to a mental health or substance abuse expert may be indicated if the teenager continues to demonstrate signs and symptoms consistent with drug use, even in the context of a negative drug test result.

Web Sites

For Teenagers and Parents

http://www.helpguide.org/mental/drug substance abuse addiction signs effects treatment.htm. This site lists signs and symptoms of drug use in adolescents.

For Health Professionals

http://www.drugfreeworkplace.com. This site lists regulations for federally mandated workplace testing programs.

http://www.acoem.org/ This site provides information on medical review officer training.

http://www.hipaa.samhsa.gov/Part2ComparisonClearedTOC.htm. This site discusses the confidentiality of alcohol and drug abuse patient records and the HIPAA Privacy Rule.

References and Additional Readings

Ahrendt DM, Miller MA. Adolescent substance abuse: a simplified approach to drug testing. Pediat Ann 2005;34:956.

American Academy of Pediatrics. Testing for drugs of abuse in children and adolescents. Pediatrics 1996;98:305.

American College of Environmental and Occupational Medicine. Medical review officer drug and alcohol testing comprehensive/fast track course syllabus. Arlington Heights, IL: American College of Environmental and Occupational Medicine; 2003.

Center for Substance Abuse Treatment. Treatment Improvement Protocol 16: Alcohol and Other Drug Screening of Hospitalized Trauma Patients. Available at http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat5.chapter.36481.

Drummer O. Review: pharmacokinetics of illicit drugs in oral fluid. Forensic Sci Int 2005;150:133.

Ehrlich PF, Brown JK, Drongowski R. Characterization of the drug-positive adolescent trauma population: should we, do we and dose it make a difference if we test?. J Ped Surg2006;41:927.

Gullberg R. Breath alcohol measurement variability associated with different instrumentation and protocols. Forensic Sci Int 2003;131:30.

Gourlay G, Heit H, Caplan Y. Urine drug testing in primary care: dispelling the myths and designing strategies. San Francisco: California Academy of Family Physicians; 2002.

Hammett-Stabler C, Pesce A, Cannon D. Urine drug screening in the medical setting. Clin Chim Acta 2002;315:125.

Hawks RL, Chiang CN, eds. Urine testing for drugs of abuse. Rockville, MD: NIDA Research Monograph 73.; 1986.

Irwin CE Jr. To test or not to test: screening for substance use in adolescents. J Adol Health 2006;38:329.

Kidwell D, Smith G. Susceptibility of PharmChek drugs of abuse patch to environmental contamination. Forensic Sci Int 2001;116:89.

Levy S, Harris SK, Sherritt L, et al. Drug testing of adolescents in general medical clinics, in school and at home: physician attitudes and practices. J Adol Health 2006; 38:336.

Med Lett Drugs Ther. Tests for Drugs of Abuse. 2002;44:71.

Schwartz R. Testing for drugs of abuse: controversies and techniques. Adolesc Med 1993;4:353.

Skipper GE, Weinmann W, Thierauf A, et al. Ethyl glucuronide: a biomarker to identify alcohol use by health professionals recovering from substance use disorders. Alcohol Alcohol 2004;39(5):445.

Verstraete A. Oral fluid testing for driving under the influence of drugs: history, recent progress and remaining challenges. Forensic Sci Int 2005;150:143.

Wolff K, Farrell M, Marsden J, et al. A review of biological indicators of illicit drug use, practical considerations and clinical usefulness. Addiction 1999;94:1279.