Urine Drug Testing -

What Do the Results Mean

and What Do I Tell the

Patient?

Andrea Trescot, MD, FIPP

Disclosure

Andrea Trescot, MD, FIPP

Pain and Headache Center

Eagle River, AK

President, Alaska Society of Interventional

Pain Physicians

Medical Director: Pinnacle Lab Services

Urine toxicology and genetic testing

Objectives

In this lecture, we will discuss:

Why do we test?

Who do we test?

When do we test?

How do we test?

What are the ethical issues involving testing?

What do I ask the patient?

What do I tell the patient?

Actual PatientCurrent Medication List

DURAGESIC 100 mg q3d – days, 10, Ref: 0

METHADONE 10 mg 1 tid – days, 90, Ref: 0

OXYCONTIN 20 mg 1 bid 30 days, 50, Ref: 0

OXYCODONE 5 mg 2-4 tabs qid – days, 196, Ref: 0

OXYCODONE/APAP 10/325 1-2 tabs qid prn, 240, Ref: 0

LORCET 10/500 1 prn, 60 Ref: 0

ALPRAZOLAM 5 mg 1 bid – days, 60, Ref: 0

KLONOPIN 0.5 mg 1 tid – days, 90, Ref: 0

CARISOPRODOL 350 mg 1-2 tabs tid – days, 180, Ref: 0

AMBIEN 10 mg ½-1 hs prn, 30, Ref: 0

BACLOFEN 10 mg 1 tid – days, 90, Ref: 0

LIDODERM 5% 700 mg 1-3 pat – days, 60 Ref: 0

DICYCLOMINE 20 mg 1 qid prn, 30, Ref: 0

POTASSIUM 20 meq 2 qd – days, 60, Ref: 0

AXERT 12.5 mg – days, 12, Ref: 4

FLONASE 2 puffs qhs – days, 1, Ref: 5

Courtesy of: Dr. Manchikanti

UDT: Positive for Cocaine and Marijuana

Negative for ALL Controlled Substances listed above

Urine Drug Testing in

Clinical Practice

Why do we test?

To evaluate patients

To support assessment & diagnosis

To monitor adherence

To identify use of undisclosed substances

To be a patient advocate

To uncover diversion

Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Urine Drug Testing

To confirm the medicines prescribed are present Depends on timing and absorbsion

To identify the presence of medicines not prescribed Need to understand the metabolism of these

medicines

Toxicology confirmation

No different than following HbA1C for diabetes, LFTs and cholesterol levels for statins, or blood pressure for anti-hypertensives

Federally Regulated Urine Drug

Testing

Most established use of urine testing

“Federal Five” marijuana (THC) cocaine (benzoylecgonine) opiates phencyclidine (PCP) amphetamine/methamphetamine

Mandated cutoff concentrations too high to be of value in clinical practice

Requirements of federally regulated testing not always applicable to clinical practice

Shults TF. Medical Review Officer Handbook. 8th ed. 2002. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Drug Detection Test in

Urine

Cutoff Level

(ng/mL)

Morphine 1 to 3 days (2 wks) 300

Methadone 2 to 4 days ( 2 wks) 300

Hydrocodone 2 to 4 days ( 2 wks) 50,000

Oxycodone 2 to 4 days ( 2 wks) 100

Benzodiazepines Up to 30 days 300

Barbiturates (short-acting) 2 to 4 days 300

Barbiturates (long-acting) Up to 30 days 300

Marijuana (chronic use) Up to 30 days 50

Cocaine (benzoylecgonine-cocaine metabolite) 1 to 3 days 300

Amphetamine or methamphetamine 2 to 4 days 1000

Typical Detection Times for Urine Testing of

Common Drugs of Abuse

Note that detection times can vary considerably, depending upon acute versus

chronic use, the particular drug used within a class, individual characteristics

of the patient, and the method used to test for a substance.

Urine Drug Testing in

Clinical Practice

Who do we test?

New patients already on controlled substances

Any patient for whom you are considering

prescribing controlled substances

Patients who are resistant to full evaluation

Patients who display aberrant behavior

Patients in recovery

Patients who request a specific drug(s)

Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

“All of my patients take their

medication as prescribed…”

BMC Health Services: 32% of

patients in primary care practice

committed opioid misuse. Negative for prescribed opioid

Positive for controlled substances not prescribed

Multiple prescribers (doctor shopping)

Diversion of opioids

Prescription forgery

Cocaine and/or amphetamines in urine (40%)

Timothy J. Ives, etal. BMC Health Services Research 2006

Urine Drug Testing in

Clinical Practice

When do we test?

Considering controlled substances treatment

Making major treatment changes

Support decision to refer

Treatment agreements

Any aberrant drug-related behavior

Third-party reports about aberrant drug-related

behaviors (family, friends, insurers, law enforcement,

etc)

Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Urine Drug Testing in

Clinical Practice How do we test?

Hair

Blood Alcohol blood levels

Saliva No point of service, no metabolites

Urine Easy, less invasive

Point of service is available

Metabolite analysis is available

Urine Drug Testing - UDS vs UDT

Urine drug screening (UDS)

Point of service (POS) or point of care (POC)

Immunoassay

Rapid, inexpensive

Table top analyzer

Chromotographic

Laboratory

Qualitative (positive or negative), no

metabolites

Multiple drug interactions

Qualitative Testing

Initial Drug Test Methods

EIA: Enzyme Immunoassay

KIMS: Kinetic Interaction Microparticulates in Solution

CEDIA: Cloned Enzyme Donor Immunoassay

FPIA : Fluorescence Polarization Immunoassay

RIA: Radioimmunoassay

ELISA: Microplate Enzyme-Linked Immunosorbent

TLC: Thin-Layer Chromatography

Baxter 2003

Urine drug toxicology (UDT)

Quantitative evaluation

Gas chromatography (GC), or mass

spectrophotometry (MS)

Metabolites

Very accurate

Urine Drug Testing - UDS vs UDT

Quantitative Testing/Toxicology

“No lower limit” allows for reporting of

results below a standard cut off

“Trough levels”

Evaluated metabolites and potential drug-

drug interactions

Can correlate with patient symptoms

Identifies “pill scraping”

Very expensive

POC vs GC/LC/MS

Urine toxicology takes time, and POC is instant

UDT Performance

Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques,

and utility. Pain Physician 2008;11:S155-180

Interpretation of Urine Testing

Results

Patient has

taken drug

Patient has

not taken

drug

Positive result True positive False positive

Negative

result

False

negativeTrue negative

Wolff K, et al. Addiction. 1999;94:1279-1298.Haddox 2005

Detection of a particular drug by a drug-class

specific immunoassay depends on

The structural similarity of that drug or its metabolites

to the reference drug

The urine concentration of that drug

The ability of the assay to detect

semisynthetic/synthetic opioids differs among

the various assays

Pitfalls of Urine Drug Screening

Opiate Screens

Natural

(from opium)

Semisynthetic

(opium-derived)

Synthetic

(man-made)

• codeine

• morphine

• thebaine

• hydrocodone

• oxycodone

• hydromorphone

• oxymorphone

• buprenorphine

• meperidine

• fentanyl

• sufentanil

• propoxyphene

• methadone

Most semisynthetic & synthetic opioids not reliably detected by commonly used screens

Shults TF. Medical Review Officer Handbook. 8th ed. 2002.

Interpretation of Urine Drug

Testing Results

Requires that you know

How specimen is collected

What is prescribed

Metabolism of drugs

Alternative medical explanations

Scams

Laws, regulations, & guidelines

Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid

analgesia. Pharmgenomics Pers Med. 2012;5:73-87.

Codeine

Codeine is

metabolized by

CYP2D6 to its

active

metabolite -

Morphine

Morphine

Morphine is

metabolized by

UGT2B7 to

M6G

(analgesic) and

M3G

(hyperalgic)

Hydrocodone

CYP2D6 CYP3A4

Oxycodone

Oxycodone is

metabolized by

CYP2D6 to its

active

metabolite -

oxycodone

Oxycodone

Oxycodone is

metabolized by

CYP3A4 to its

inactive metabolite -

noroxymorphone

Tramadol

Tramadol is

metabolized by

CYP2D6 to its

active

metabolite – O-

desmethyl-

tramadol

Fentanyl

Fentanyl is

metabolized by

CYP3A4 to its

inactive

metabolite -

norfentanyl

1901

Any recent cough medication?

Heroin

6-MAM

Heroin

Methadone is metabolized by

CYP3A4 to the inactive EDDP.

Secondary metabolism by 2B6, 2D6

Diazepam

THC -- Marijuana

THC Testing

Marinol (A synthetic THC) is prescribed for nausea

and weight gain- tests positive

Casamet ( a synthetic cannabinoid) is marketed in

Canada, tests NEGATIVE

Sativex (also Canada) contains THC—will test

positive.

CBD (now available OTC) may or may not contain

THC – depends on the source (marijuana vs hemp)

Poppy Seeds Causing Morphine?

UDS Cross Reactions

Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques,

and utility. Pain Physician 2008;11:S155-180

Additional Methadone False

Positives

Verapamil (Calan®)

Doxylamine (Unisom®)

Cyamemazine (Tercian®)

Alimemazine (Nedeltran®)

Levomepromazine (Nozinan®)

Thiordazine (Mellaril®)

Olanzapine (Zyprexia®)

Lancelin F et al. False positive results in the detection of methadone in urines of

patients treated with psychotropic substances. Clinical Chem 2005;51:2176-

2177

UDT PCP Cross Reaction

Roche DAT Handbook 1.1

UDT THC Cross Reaction

Roche DAT Handbook 1.1

Amphetamine

Medical Explanations for Positive

Results: Amphetamine/Methamphetamine

Prescription medication

Adderall®

Cross-reaction with structurally similar

prescription drugs for Parkinson’s disease &

OTC diet agents & decongestants

dopamine, isoxsuprine, ephedrine, phenmetrazine,

phentermine, fenfluramine, mephentermine

Drugs metabolized to amphetamine/

methamphetamine

Selegiline (for Parkinson’s), benzphetamine,

dimethylamphetamine, fenproporexShults TF. Medical Review Officer Handbook. 8th ed. 2002.

Screen and Confirm

Urine Results Reported as

“None Detected” May mean any of following

Patient Does not use drug

Has not recently used drug

Excretes drug/metabolite faster than normal

“Peak and trough” levels

Urine testing used was not sufficiently sensitive to detect drug at concentration present Ask for “no threshold” testing (GCMS)

Clerical error (wrong sample)

In adherence testing, may raise concerns about misuse/diversion

Wolff K, et al. Addiction. 1999;94:1279-98. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph].

2004.

Common Errors of Interpretation

Patient taking hydrocodone

Urine screen for opiates is listed as “morphine”; result reported as positive

Patient accused of not adhering to treatment plan & discharged

GC/MS confirms hydrocodone & hydromorphone

Solution: understand POC testing

Explaination: Some cups label “opiates” as “morphine”

Haddox 2005Added by Jordan

Common Errors of Interpretation

Patient taking oxycodone

Urine screen for “opiates” reported as

“none detected”

GC/MS not performed

Patient accused of not adhering to

treatment plan & discharged

Solution: order GC/MS

GC/MS=gas chromatography/mass spectrometry

Von Seggern RL, et al. Headache. 2004;44:44-7.

OXYCODONE

The “Federal Five” screen does NOT include oxycodone

Standard POCT immunoassay will NOT reliably detect oxycodone under the

OPIATE group

Specialized oxycodone immunooassay now available

Urine Toxicology - Metabolites

Urine Toxicology

- Stopped Taking Meds

Methadone and Buprenorphine

Other Testable Drugs

Urine Drug Testing in

Clinical Practice

What are the ethical issues involved in urine drug testing?

Ethical Perspectives

A false-negative or false-positive result

can have a significant impact on a

patient’s access to pain management.

Prescribing physicians should always be

cognizant of the limitations that urine drug

screens present.

The results of these tests should not be used

in isolation to diagnose addiction nor should

they dictate management decisions without

clinical context.

Ethical Perspectives

The most common scenarios faced when

interpreting urine drug test results are 1) the urine sample is positive for prescribed drugs and

negative for all other prescribed or illicit drugs

2) the urine sample is positive for illicits or non-

prescribed opioids

3) the urine sample is negative for the prescribed

opioids

4) the urine is negative for the prescribed opioids and

positive for ilicits

Ethical Perspectives

The immense magnitude of the revenue

streams associated with drug screens may

potentially influence prescribing physicians

to routinely incorporate screening into their

practice.

Diagnostic laboratories have benefited

from the growth in urine screens with

revenues purported to have surpassed $2

billion in 2013

Pain Physicians, and Testing

Labs, Have Been at the Center

of the Increase in Urine Testing

Medicare data demonstrates that the total number of drug tests

reimbursed at physicians’ offices increased from 101 tests

performed in 2000 to over 3.2 million in 2009

Urine Testing Costs are

Increasing and Threatening

Access

Fraud Comes at a Steep Price

Random Testing vs Routine Testing

No evidence to support either

First visit, any unexpected problems, dose

escalation, early refill request, periodic.

Patients at higher risk for abuse might

require more frequent screening.

Screening consistently helps to normalize

the routine nature of providing a specimen.

It makes the request less awkward during an

encounter that is complicated by subversion

and otherwise warrants a UA.

How Often is Enough but Not

Too Much?

Some specialists recommend 3 random

screens (POC) within the first 12 – 15

months of therapy and once annually

afterwardsOwen GT, Burton AW, Schade CM, Passik S. Urine drug testing:

Current recommendations and best practices. Pain Physician 2012;

15:ES119-E133.

However, that does not assess “pill

scraping” and adulterated urines

Deception Techniques

How Often is Enough but Not

Too Much?

Consider intermittent toxicology

Initial assessment

When medications “stop working”

With “red flags”

Medical necessity

How will this change your treatment?

“My Meds Stopped Working”

Drug-Drug Interactions

Diagnostic Dilemmas

Morphine > 6400

Norhydrocodone 36

Hydromorphone 57

Oxycodone >6400

Noroxycodone >6400

Oxymorphone 148

MSER 120mg TID

Oxycodone 30mg q 4 hrs pain score 9/10

Morphine With Hydromorphone

Drug Impurities

Urine Drug Testing in

Clinical Practice

What do we ask the patient?

How well is the medication working? “How long before you notice an an effect?”

“How much relief do you get?” % improvement

“How long does it last?”

This helps to create a “dose/response curve”

6 12 18 24

analgesia

toxicity

8

Other Things to Ask…

What is going to be in your urine today?Establishes trust and allows for “on-the-spot” counseling

“Tell me about how you are taking the

medication”

“Tell me about times that you miss or don’t

take the medication”

“Tell me about how you secure the

medication and who has access to it.”

Urine Drug Testing in

Clinical Practice

What do we tell the patient?

If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.

If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will not be any consequences)

If no active metabolites, consider changing medications

Diagnostic Dilemmas

Morphine > 6400

Norhydrocodone 36

Hydromorphone 57

Oxycodone >6400

Noroxycodone >6400

Oxymorphone 148

MSER 120mg TID

Oxycodone 30mg q 4 hrs pain score 9/10

Morphine >64000

Urine Drug Testing in

Clinical Practice

What do we tell the patient?

If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.

If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will less consequences)

If no active metabolites, consider changing medications

No Metabolites

What Do You Do Now?

Discuss why they adulterated the urine.

Consider the risk of continued opioid

prescribing.

Closer monitoring

Consider buprenorphine

Based on the therapeutic relationship, an

alternative to immediate discharge may be

referring the patient to an addiction

specialist.

“A cry for help”

Urine Drug Testing in

Clinical Practice

What do we tell the patient?

If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.

If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will be less consequences)

If no or low active metabolites, consider changing medications

Diagnostic Dilemmas

Morphine > 6400

Norhydrocodone 36

Hydromorphone 57

Oxycodone >6400

Noroxycodone >6400

Oxymorphone 148

MSER 120mg TID

Oxycodone 30mg q 4 hrs pain score 9/10

Changed to oxymorphone

Alcohol Toxicology – A Chance

to Discuss

Acc VTA

FCXAMYG

VP

ABN

Raphé

LC

GLU

GABA

ENK OPIOID

GABAGABA

GABA

DYN

5HT

5HT

5HT

NE

HIPP

PAG

RETIC

To dorsal horn

END

DA

GLU

Opiates

ICSS

AmphetamineCocaineOpiatesCannabinoidsPhencyclidineKetamine

OpiatesEthanolBarbituratesBenzodiazepinesNicotineCannabinoids

OPIOID

HYPOTHALLAT-TEG

BNST

NE

CRF

OFT

I would suggest quantitative UDT

(or UDT)

Consider addiction referral/discharge

Continue opioids

Nonopioid treatment

Addictionology referral

Discharge

Their Conclusion

Summary:

Before You Order a UDT

Ask patient

Are you taking any prescribed, OTC, or

herbal drugs?

When was last dose? Quantity?

Drug misuse/addiction history

Let laboratory know what you are looking for

Illicit substance

Prescription drug misuse

Presence of prescribed medication

Summary

Give the patient the benefit of the doubt

Minimize doubt through education and

collaboration, but understand that drug

testing remains an evolving field and there

are several aspects (specific metabolites,

metabolite concentrations, metabolite

ratios, assay limitations, interferences) that

are incompletely understood.

Summary (continued)

False accusations of abuse or diversion

are unacceptable and may impact the

patients’ ability to receive appropriate

present and future care.

The diseases of abuse and addiction are

chronic and often progressive, and are

rarely (if ever) made on the basis of a

urine drug test.

Place drug testing data in the context of

the total clinical picture.

Summary - Continued

Finally, have an action plan. What will you

do with the results?

Depending on the situation, this may entail

no special action; close observation;

challenges to change behavior; tightening

of treatment boundaries; consultation with

an addiction medicine specialist; or referral

to a drug treatment center.

Reisfield G. Pitfalls in urine drug test interpretation. The Pain

Practitioner 2009;19(3):16-24

Thank you!

Andrea Trescot

DrTrescot@gmail.com