We often receive inquiries asking if quantitative drug metabolite levels reported for a particular drug screen result can show whether or not a client has abused a prescription by taking more than a therapeutic level. There is universal agreement among toxicologists that urine drug screen results should only be used to determine whether a particular specimen is positive or negative. While metabolite levels are reported on those results, those values are indicated purely to demonstrate that the concentration of metabolite exceeds the cut-off level and can therefore be indicated as positive. However, as the question has been coming up more and more frequently we decided to investigate the matter further. To do so we engaged the services of a nationally known specialist in addiction medicine, Mark Weiner, MD.
Because we have also been asked by clients if oral fluid metabolite levels could be used to make that same kind of determination, we asked Dr. Weiner to look into that as well. Following is his White Paper on the subjects, developed through an extensive literature review, and consultation with fellow addiction medicine physicians and toxicologists. I hope you find it as interesting and informative as we did.
As an experienced clinician who routinely treats patients with chronic pain and addiction, I am often asked by the referring doctors whether a particular patient is taking their medication as prescribed. The purpose of this paper is to clarify my opinion and experience by responding to four questions that commonly arise.
What is the best methodology to determine if an individual is taking prescription medication as prescribed or abusing that medication?
In clinical practice, this is often rather challenging. In some cases of active addictive illness, the patient is unwilling or perhaps incapable of being forthcoming and honest regarding his or her use of medication. The generally accepted practice of determining if abuse or addiction is taking place, involves a careful interview by an experienced clinician. This is considered the “gold standard.” In general, if a patient is suspected of exceeding their prescribed limit of medication, one would pay careful attention to several factors. These factors include timing of medication refills, whether there are additional providers prescribing medications, evidence of running out of medications earlier than expected, or the presence or absence of signs of withdrawal consistent with abrupt discontinuation of a medicine for which a patient may be dependent.
Toxicology of body fluids can play an important role in both determining whether a patient has run out of their medication early or is on medications other than prescribed. The most commonly used fluid for testing is urine. Urine has a significantly longer detection window compared to blood or oral fluid. It can clarify whether a patient has discontinued intake of their medication if it is absent upon urine testing. It could also identify other substances that would not be recommended or are unauthorized. Obtaining confirmation by the court room-accepted method, gas chromatography/mass spectroscopy, is particularly helpful as the standard screen (immunoassay) is not very specific. It is helpful for the clinician to be appropriately trained in interpreting the results of these tests. In general, the most expert professionals in interpreting fluid toxicology are the medical review officer (MRO), clinical pathologist, and addiction medicine specialist.
Due to a significant variance in drug levels after ingestion as well as differences in drug metabolism, the literature suggests that, at present, it is not possible to determine if a patient is abusing medication or taking it as prescribed by using ANY form of fluid testing. I have discussed this with clinical laboratory specialists who agree that observed urine or oral fluid testing can only be used qualitatively and not quantitatively. Because of its shorter detection window, oral fluid is known to detect very recent usage (within 24 to 36 hours) but neither saliva nor urine can conclusively identify quantitative abuse.
Most states offer a controlled substance monitoring system to help identify if patients are receiving multiple controlled substances from different providers. In Michigan, this is the Michigan Automated Prescription System or MAPS. Any licensed practitioner can receive a login for the MAPS System and can quickly identify exactly when patients are having their prescriptions filled and if there are additional prescribers. Often this provides more accurate information than that which is obtained in the patient record, as the patient record only identifies when a prescription is created and distributed. Receiving multiple controlled substances from different providers is particularly concerning and sometimes dangerous. Many practitioners involve the use of a treatment agreement that clearly identifies only one authorized prescribing practitioner for controlled substances.
When interviewing the patient, certain techniques are more helpful in identifying use of medications outside the prescribed regimen. For instance, patients may not quickly respond in the affirmative to a question such as, “Do you overuse your medications?” They may respond better to, “Do you sometimes find that you do not have enough medications to make it until the end of the month?”
Another important distinction to make is between the overuse of a medication due to addiction versus “pseudo addiction.” In “pseudo addiction”, patients are not using the medication addictively, but are running out early as they are attempting to treat their pain, and have developed tolerance such that the prescribed regimen is ineffective. In many ways, teasing out true addiction versus “pseudo addiction” is difficult to delineate.
What is the best methodology to determine if an individual has achieved but not exceeded therapeutic levels of a particular medication?
To answer the next question, it is important to note that the therapeutic level of most drugs is normally not determined, nor would it have any practical meaning in the treatment of most patients for most conditions. There are some notable exceptions and these are usually drugs that have a long half-life, an easily determined serum level, a known therapeutic level or an untoward effect if the level is exceeded. Common examples of antibiotic exceptions include gentamicin and vancomycin. Anticonvulsants that can be monitored include phenobarbital, phenytoin, and carbamazepine. For pain management, the only drug that is commonly measured is methadone. This is because methadone has a sufficiently long half-life such that a stable state is encountered after the medication has been taken consistently for five to seven days. There are also commonly accepted levels for analgesia as well as other levels for methadone important for the treatment of opiate addiction. It is also important to note when methadone is at a toxic level. At that point, the only commonly accepted measurements involve the use of serum levels. Although advances have been made in oral fluid testing, there is not, as of yet, any generally accepted use of oral fluid levels for methadone in clinical practice.
A review of the literature combined with long professional experience suggests that there is no generally accepted method for determining the therapeutic efficacy of short-acting opiates, sustained-release opiates, or similar medications based on any particular fluid level.
What is the value of oral fluids test results in determining proper use or abuse of a prescribed medication?
Depending on the particular clinical presentation and history, a clinician can either select oral fluid or urine drug testing as the method of choice. A benefit of oral fluid testing is that it is convenient to administer and –-resistant (although not immune) to adulteration. Although a properly conducted observed urine collection procedure coupled with validity and adulterant testing at the lab could be said to be equally resistant to adulteration. . An additional benefit is that in certain cases, patients may be unable to provide a urine sample, yet oral fluid sampling is usually readily available. In regard to determining whether or not a drug is being used, oral fluid and observed urine are both effective, although the longer window of detection inherent to urine testing is a definite advantage in cases involving the need for ongoing random compliance or where testing is in any way predictable. . The quantitative levels of either cannot conclusively determine whether a substance is being used within the prescribed regimen or not. However, complete absence of substances that should be present or the identification of substances that should not be present are extremely important pieces of information in determining medication compliance and identifying patient risk.
What are commonly accepted practices in medicine or toxicology in regard to determining if medications are at therapeutic levels through oral fluid testing?
At present, the levels identified through oral fluids testing are not clinically significant, nor can they be used to quantitate the amount of medication taken by a particular patient. Although oral fluid testing levels may indicate very recent usage, there exists no generally recognized application for these levels in clinical practice. Oral fluid testing results can only be used qualitatively and not quantitatively.
Mark A. Weiner, M.D.
Board Certified Internal Medicine
Board Certified Addiction Medicine
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Mark Allen Weiner, MD, earned his undergraduate degree from the University of Michigan, his Doctorate of Medicine degree from Cornell University, and completed both his Internship and Residence in Internal Medicine at Northwestern University Medical Center. He is Board Certified by both the American Board of Internal Medicine and the American Board of Addiction Medicine.
Dr. Weiner currently serves as Medical Director of Pain Recovery Solutions, PC., in Ypsilanti Michigan, and also provides treatment and consultation in Internal Medicine, Addiction Medicine, and Pain Management at St. Joseph Mercy Hospital, Ann Arbor, Michigan, where he serves as Section Chief of Addiction Medicine.
A nationally recognized expert in Addiction Medicine, Dr. Weiner is the editor of the American Society of Addiction Medicine Pain and Addiction Management Handbook (to be published in 2015), and is co-chair of the planning committee of the American Society of Addiction Medicine course, Pain and Addiction: Common Threads. Additionally, he serves on the board of Dawn Farm Treatment Centers, and is the chairman of the treatment subcommittee.