Introduction Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 References

The Patient Scenario
A female patient is newly referred to the pain management practice. At her initial visit, the patient’s risk assessment scores indicate she is at high risk for substance abuse, misuse and addiction. The patient states she is currently prescribed controlled-release morphine sulfate 100 mg, twice daily for chronic pain. The patient is in recovery from heroin addiction for five years.

As part of the assessment of the patient, an immunoassay urine drug test (UDT) sample is collected in the office and sent to your outside lab. The UDT is to assist in assessing patient compliance with her prescribed therapy and to rule out relapse to her previous drug of choice, heroin.

The Test

Laboratory immunoassay testing with triggered confirmatory testing of positive results.

The Test Results
Her immunoassay was positive for “opiates” which were identified as morphine, trace hydromorphone and codeine by confirmatory testing.

Results do not show the presence of 6-monoacetylmorphine (6-MAM). Trace hydromorphone is consistent with high-dose morphine use through a minor metabolic pathway or less likely, through use of hydromorphone containing products.

The Test Interpretation

Given the UDT results (which include codeine), which of the following best explains these results?




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What do you believe should happen next?





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While it is wise to avoid the chronic use of any medication which would make identification of relapse difficult/impossible, in cases where the patient genuinely is doing well, many experts would be reluctant to make a change to another drug simply based on this fact alone.

What if the urine drug test results were reported positive for 6-MAM?
Is this patient:




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Heroin, a semi-synthetic opiate, is rarely detected in its pure form in body fluid samples, as heroin’s elimination half-life is 3-6 minutes. 6-Monoacetyl morphine (6-MAM/6-AM) is a short lived intermediary that is considered definitive evidence of exposure to heroin.

Heroin use is detected by presence of its metabolite: 6-monoacetylmorphine (6-MAM) in low concentrations; morphine; and codeine (codeine may be a component of illicitly manufactured heroin formulation; 5%-10%).

6-MAM is formed only by metabolism of heroin. It is a definitive marker of recent heroin use if detected in the urine sample.

Absence of 6-MAM does not rule out heroin use. 6-MAM has a short half-life (t½=25-30 minutes) and so is frequently absent from even recent heroin use.

A urine sample that tests positive for 6-MAM should be considered positive for heroin use.

The Physician’s Next Step
The patient has slipped to the use of some Tylenol #3 that was previously prescribed to her for dental pain.  Given the confusion that this has caused, the patient and prescriber agree to a trial of methadone for the treatment of her pain with more frequent UDT to successfully optimize analgesic effect and to manage risk. After successful rotation to methadone for analgesia, a follow-up UDT sample is collected from the patient two weeks later.

Although urine test results are not always definitive markers of compliance status, test results can provide additional data in an objective patient-centered fashion.

It may be easy to project bias toward the patient due to her past report of heroin addiction, and the prescriber may choose not to continue prescribing an opioid analgesic.

As a general rule, it is unwise to chronically prescribe specific members of classes of drug which have previously been misused by the patient. In this case, morphine is a common metabolic endpoint for heroin use and so will always complicate the interpretation of the UDT of a former heroin user.

Additional unbiased diagnostic information is necessary to optimize future decision making.

Confirmatory Urine Drug Test Results
Repeat test results from comprehensive/confirmatory urine drug testing are reported as positive for codeine, morphine and EDDP* (methadone metabolite).

How do you interpret these new urine drug test results?




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Test Interpretation
The absence of 6-MAM makes definitive statements about heroin relapse unwise; however, the ongoing presence of morphine/codeine, two weeks after discontinuing controlled-release morphine and initiating methadone is not consistent with adherence to the agreed upon treatment plan.

A lab urine immunoassay test will not provide all of the information needed to understand what is really going on with this patient.

Unless the urine sample tests positive for 6-MAM, further exploration is required. A physical exam looking for stigmata of active drug misuse, such as needle track marks and further assessment of the patient’s risk for drug abuse, misuse, and addiction is suggested.

The ongoing presence of unprescribed drugs (morphine/codeine) makes continued prescription of any controlled substance unwise. Given her past history of heroin dependency, a dominant substance use disorder must now be considered. While this diagnosis does not negate the patient’s complaints of pain, it complicates treatment.

The differential diagnosis for ongoing use of morphine-containing products includes inadequate treatment of pain (ie, pseudoaddiction), however the resources and experience needed to safely assess and manage this problem may be beyond the scope of most primary care clinicians.

As described in “Universal Precautions in Pain Medicine,” this patient fits the “Group III” category of high risk, active user and should be formally referred on to someone with greater experience and more resources in treating such complex patients.

While it is useful to try and avoid previously misused drugs, especially when used chronically, the decision to change medications in an otherwise stable patient must be made on a patient-by-patient basis.
UDT is only one piece of information necessary to properly diagnose and treat aberrant behavior.
As a rule, it is unwise to prescribe therapeutic agents which make the identification of relapse difficult or impossible. For this reason, morphine was a poor choice of analgesic, given the patient's past drug history. For similar reasons, codeine is to be avoided.

The Final Outcome
After reviewing the lab results with the patient, she acknowledged supplementing her pain relief with heroin. She was referred to an addiction medicine specialist for assessment. After conversion to sublingual buprenorphine maintenance therapy, her pain is now well managed with non-opioid adjuvant therapies.

*EDDP= 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine


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Case 1:
Low back pain

Case 3:
Activity-related pain

Case 4:
Escalating opioid doses

Case 5:
Opioid-dependent
pain patient

Case 6:
Comorbid depression & anxiety