Thursday, 10/01/2009 at 2:24 PM

Discovering the Invisible Patient with Pharmacogenetic Testing

Magnified DNAWe are discovering more and more the important role genes play in how our bodies process drugs. Pharmacogenetic testing provides a way to look at a patients’ genes that play a role in drug metabolizing. Identifying unique characteristics of these genes can assist in individualizing pharmacotherapy for chronic pain treatment.1

Clinicians understand that visible differences between patients, such as age and weight, can affect how that patient will respond to pain treatment. What is currently less understood are the important invisible differences that also affect therapy. A primary cause of variation in drug response is interindividual variations in the genes that encode for the “proteins and enzymes involved in the transport and metabolism of drugs”.2 As Meijerman explains, “interindividual differences in the pharmacokinetics (PK) of drugs represent a major clinical problem. Because of these differences, plasma levels of drugs are poorly predictable, which might lead to unexpected toxicities or undertreatment of patients”.2 By identifying these genetic variations through a one-time genetic test, we can better prescribe a pharmacotherapy regimen that is optimal for each individual patient.

Specifically, “it is the role of the highly polymorphic CYP2D6 gene that is of the greatest clinical interest with respect to the observed interindividual variability in the opioid response”.1 The CYP2D6 gene metabolizes many drug classes, including the opioids. Variation in the DNA encoding for these enzymes can cause them to metabolize faster or slower.1 As also illustrated in the UDM handbook:

DNA sequence variations are associated with:

  • Lack of enzymatic activity (poor metabolizer)
  • Reduced enzymatic activity (intermediate metabolizer)
  • Enhanced enzymatic activity (ultra-rapid metabolizer)

“The use of CYP2D6 genotyping to make therapeutic recommendations to improve therapeutic efficacy and to prevent toxicity in patients is promising and clinically relevant”.2 Pharmacogenetic testing can provide us with “invisible” genetic information on a patient’s propensity for a drug reaction that allows us to further objectify each individual’s pain regimen, and thus minimize the practice of trial-and-error prescribing.1

  1. Urine Drug Monitoring: Opioids Handbook
  2. Meijerman Irma, Sanderson Linda M., Smits Paul, Beijnen Jos H., Jan H.M. Schellens. “Pharmacogenetic Screening of the Gene deletion and Duplication of CYP2D6.” Drug Metabolism Reviews, 39: 45–60, 2007.

Posted in: Pharmacogenomics

Friday, 06/05/2009 at 12:54 PM

Using Risk Stratification to Determine Testing Frequency for Patients on Long-Term Opioid Rx

IStock_000004381367resizeOne question I’m frequently asked by other clinicians is, “How often should I be testing my chronic pain patients?”

When I ask how they currently determine testing in their practice, the answers range from “I don’t test because I know my patients” to “We roll dice when the patient registers.”

In my experience, physicians as a group have concerns regarding their ability to distinguish low risk patients from those who will likely require frequent monitoring. This concern can lead to a reluctance in prescribing long-term opioid medication.

A smart and frequently used strategy to establish testing frequency is based on stratifying patients based on risk. There are several risk assessment tools available for clinical use. While most clinicians are aware of these tools, there has been little information on how to implement the results (e.g., determine testing frequency). In February 2009, an article funded by the American Pain Society titled Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain recommends using a risk assessment tool along with a History, Physical Exam and other appropriate testing before initiating chronic opioid therapy (COT). According to these guidelines, “Tools that appear to have good content, face, and construct validity include the Screener and Opioid Assessment for Patients with Pain (SOAPP) Version 1, the revised SOAPP (SOAPP-R), the Opioid Risk Tool (ORT), and the Diagnosis, Intractability, Risk, Efficacy (DIRE) instrument.” Monitoring recommendations for patients at low risk for adverse outcomes is at least once every 3 to 6 months, patients at very high risk could require monitoring on a weekly basis. Those patients falling in between these 2 categories would include those prescribed a change in opioid dosage, patients with an addicting disorder, older adults, those in an occupation demanding mental acuity, patients with an unstable or dysfunctional social environment and those with comorbid psychiatric or medical conditions.

I have personally used the SOAPP-R with good success and have recommended it to others. This 24 question self-report questionnaire is designed to aid in the process of determining which patients are at high risk for opioid misuse. Scores stratify patients into low, moderate and high risk categories. I have recommended UDM intervals as follows:

SOAPP-R ScoreRisk LevelMonitoring Frequency
0-9Low1-2 times per year
10-21Moderate4-6 times per year
22+Highweekly initially, then every visit

Keep in mind, the patient’s level of risk can change over time. It’s important to perform serial risk assessment surveys to restratify your patients. Also, there are differences between the available tools. You should choose the one that works for your practice.

Risk assessment tools like SOAPP-R are a simple, proven way to evaluate a patient’s potential for misuse. However, these tools should not be relied on exclusively as other monitoring techniques may also indicate high risk (e.g., illicit drugs detected in urine drug testing). For those patients who are high risk, combining UDM with pill counts, frequent follow-up visits, use of prescription monitoring programs (PMP) and family member interviews is an effective and reasonable monitoring strategy.

Posted in: Addiction , Patient Surveys

Wednesday, 05/27/2009 at 11:46 AM

4 No-Cost Ways to Break Down the Patient-Clinician Communication Time Barrier

Clinician with alarm clockOpen and thorough patient-clinician communication is important both for efficacy of treatment and efficiency of office visits. Certain barriers can impede this. For patients, these barriers may be psychosocial factors such as personality, beliefs, socio-economic status and/or conceptions about their treatment. Additionally, patients can underestimate their own importance in the outcome of their pharmacotherapy. While certain psychosocial dynamics can also be a factor for clinicians, a commonly cited communication barrier is a lack of time. Studies and research have sought to address these issues in communication by developing methods to improve the clinician-patient relationship. By incorporating these methods with the use of laboratory diagnostics, medical history and pharmacogenetic data, clinicians are able to enhance the quality and efficiency of health care through more accurate diagnostics, improved patient adherence, increased patient satisfaction and decreased malpractice litigations.

Some patients may refrain from openly communicating with their clinicians out of fear that they will be perceived negatively. As demonstrated my blog entitled “Real-Life Opportunities to Improve Pharmacotherapy,” patients may endure needless pain because they do not want to “upset” anyone or be viewed as “a difficult patient.” Patients should understand that by telling us how they are responding to treatment they are contributing in a proactive manner that is important to individualize and improve their pharmacotherapy. The following ideas may help us to portray this to patients:

  1. Build Trust and Encourage Open Communication: According to a comprehensive review of studies on patient-clinician communication and relationships, “A warm greeting, eye contact, a brief non-medical interaction, or checking on an important life event can build rapport in less than 1 minute.”1 These gestures improve the course of treatment for both clinician and patient by developing a mutually beneficial relationship; and, they require virtually no additional time the office visit.
  2. Understand Patients as Individuals: Empathizing with our patients’ concerns about their treatments and understanding them as individuals allows us to take into account what psychosocial factors may be affecting their pharmacotherapy. This in turn improves our ability to create a pharmacotherapy that is specific to them, enhancing its efficacy and reducing the need for future adjustments.
  3. Ensure that Patients Understand Their Treatment: Clinicians can take a preventative approach to improving adherence by eliminating confusion (e.g., complex regimens) and helping patients understand all aspects of their treatment. Opening up this dialogue also aides in creating an environment where patients can candidly discuss any other factors affecting adherence.
  4. Offer Suggestions to Improve Communication: As clinicians, we can also offer patients suggestions to improve communication, such as writing down their questions before they come to their office visit. This helps assure that all of their concerns are addressed, reiterates the importance of their active role in their treatment, and ensures that the office visit is utilized most effectively.

Better communication leads to better treatment, and neither requires any extra time. In effect, establishing an open and communicative patient-clinician relationship can save future time spent adjusting and making changes from miscommunication or factors affecting adherence that could have been addressed if communicated initially. Psychosocial factors or concerns about how their clinician perceives them may inhibit some patients from openly communicating with their clinician. Alleviating these concerns can help to create an environment where patients feel comfortable disclosing all information pertinent to their pharmacotherapy and can help patients to understand the importance of doing so. Employing empathy and education strengthens the patient-clinician relationship and results in better treatment and more satisfied patients. Patient satisfaction has been shown to decrease malpractice litigations. Information provided by patients regarding the effects of their treatment can be used with laboratory diagnostics, medical history and pharmacogenetic data to further individualize pharmacotherapy and improve the quality of health care.

  1. Roxanne Nelson and Charles Vega MD, Improving Communication Skills Enhances Efficiency and Patient-Clinician Relationship. Medscape Medical News 2008.

Posted in: Patient/Clinician Relationship

Tuesday, 05/19/2009 at 2:49 PM

Prescribing Opioids For Chronic Pain Patients Who Use Marijuana - A Clinical Perspective

IStock_000000693469XSmall-resize A recent reader comment asks the question, "What should be done by a primary physician when a patient intended to be on chronic opiates is using marijuana, especially when repeatedly positive on testing or outright admitting that marijuana use is ongoing?" In an effort to respond, I requested a clinical opinion from my friend and colleague, John Femino, MD, FASAM. John’s response, provided below, outlines his clinical experience with this common scenario. John’s approach aims to involve patients in the therapy process to best understand the reasons behind illicit marijuana usage.

As the reader notes, marijuana use is extremely prevalent in society and the drug has historically been labeled as the most commonly used illicit substance. The current trend of medical marijuana widens the use of the drug in clinical settings across the United States. The reader remarks that marijuana usage is not widely covered in research or educational discussions in the field.

John’s response recognizes both illicit and medical marijuana use as common concerns of clinicians. John provides a usable, practical strategy for prescribing physicians of various medical specialties to treat or refer patients in this scenario, rather than deny them necessary treatment.

“David – The situation is quite analogous to the issue of using/abusing opiates from other sources than the doctor who has been prescribing medication. In Rhode Island, we come across this every day with the advent of the Medical Marijuana Law. Although I feel that the issue of the legality and the proximity of the user to other illicit drugs is a valid concern, it is one that is true for all patients and not just the individual patient on prescribed medication.

I prefer to view this problem as one that’s amenable to a risk benefit analysis – whether the person is getting any benefits from the marijuana use, is experiencing any side effects, or is having other co-morbid problems associated with the chronic pain (e.g., depression, anxiety disorder, sleep, cognitive disturbance, memory problems, or other behavioral issues such as isolation and withdrawal). If the chronic marijuana use is worsening or interfering with the management of the underlying condition, then the risk/benefit profile for ongoing marijuana use would suggest that the treating physician should recommend that the marijuana use be stopped. Since marijuana may be helping the pain control issues, I also suggest that the physician utilize pain scales, pain diaries, and any other patient centered data collection devices that might assist in getting a better “movie” of the impact of the marijuana use on these conditions and complaints. In our experience, when we utilize pain scales to document the effectiveness of marijuana on pain relief, we find that it is very short-lived, paralleling the perceived high and often associated with numerous “side effects”. The experienced marijuana abuser usually experiences the “side effects” as the “desired effect”, whereas the marijuana naïve individual experiences the side effects as an undesired effect, representing for them the “stop signal” rather than the “Ah signal”.

Clearly the most significant benefit of this approach is that it is specific to each individual patient, and demonstrates to the patient that the effect of marijuana is interfering with the medical management and overall course of monitoring prescribed medications and other therapeutic approaches. I emphasize that for most patients in this situation that the side effects will confuse the physician’s interpretation of the patient’s symptoms, possibly exposing them to more medications that could have more significant and potentially dangerous side effects than the marijuana itself. I furthermore point out that most chronic marijuana users are also poly substance users and that adding marijuana to chronic opiates could set them up for relapse back to their drug of choice.

I much prefer a dialogue over the medical risks and benefits than a legalistic approach or one that discharges the patient from appropriate medical care, simply because of their use of illegal substances. On the other hand, we frequently discharge patients for chronic marijuana use because the use represents abuse and dependence and has resulted in more complicated clinical course than if the patient was on alternative medications or non medication treatments.

Documentation in the medical record would include these discussions as well as a quantitative creatinine adjusted cannabinoids level. Often we find that these patients have extremely high levels of marijuana in their system, such that presenting it back to the patient can demonstrate to them that their use may be interfering with other prescribed medications. If the patient listens carefully to your concerns as the primary prescriber, they will make adaptations based upon your suggestions to come up with a better therapeutic alternative. If the patient resist these recommendations and refuses to adapt their marijuana usage despite well-documented negative consequences of the marijuana use, then documentation in the medical record will assist in any medical legal challenges. Documentation of this information into the medical record including a diagnosis of marijuana dependence, can now be presented to the patient and coded on the appropriate billing forms. Most patients get quite concerned when their records reflect that their use is being documented as abuse or dependence rather than their personal preference for a drug that they believe should be legalized. For those primary care physicians who are in this situation, we recommend that an addiction medicine evaluation be performed. Documentation of that consultation in the medical record will also assist in the event of a regulatory review.

For the patient who persists in smoking marijuana despite such documentation and refusal of treatment recommendations, then the primary care physician should consider transfer of that patient to an addiction specialist who can manage their chronic pain and addiction to the marijuana itself. Such patients now have to make a choice that can be an opportunity for them to learn more about their marijuana use as well as reflect upon the importance of their therapeutic relationship with their prescribing physician.

We also like to point out to the patient that their choice of jeopardizing an important therapeutic relationship in their life is indicative of the seriousness of marijuana dependence. Those patients who truly have a terminal condition or one in which their use of marijuana truly has a favorable risk benefit ratio, then the physician can decide that continued use of marijuana is acceptable and will be continue to be monitored closely in the future. In this way any time delay that may be necessary to collect for the data is documented, rather than being viewed by a regulatory agency as “looking the other way”. Our experience with this approach has demonstrated that those patients, who have tried marijuana and found it helpful, may now find with a more careful scrutiny, that other side effects that they had attributed to other medications were really from the marijuana, thereby, assisting them in cooperating with the recommendation to cease marijuana use. For those states that have passed medical marijuana laws, this approach allows an individual basis specific recommendations that are based upon each patients set of symptoms, circumstances, and other environmental situations. It also avoids the endless arguments about legalization by focusing completely on the effect of the drug rather than its legal status.

I hope that this information is useful and I would be glad to participate in any further discussions regarding these topics – John Femino, MD, FASAM.”

John provides a usable strategy for approaching patients being treated in primary care, pain management, addiction medicine and other specialties. There are always, of course, individual case scenarios that will require more or less effort than John suggests. This “hot button” topic of marijuana use will continue to present us with challenges in the clinical setting. Ultimately, as the reader suggests, it’s about treating the “whole” patient. We recognize that there are certainly more viewpoints from a clinical perspective. Please add your opinions and case examples from your experience in the comments.

Posted in: Illicits , Medical Marijuana

Tuesday, 05/12/2009 at 3:09 PM

Real-Life Opportunities to Improve Pharmacotherapy

clinician with elderly patient My friend, who is in her eighties, was recently hospitalized for back surgery and then stayed at a nursing home/rehabilitation center after her hospital discharge. Both in the hospital and in the nursing/rehabilitation facility, she was under-treated for her pain. In the hospital, she was prescribed hydrocodone as needed (PRN) and morphine around the clock (ATC). She was not being administered her morphine ATC and was mostly being administered hydrocodone which did not alleviate her pain. Only after I spoke with her clinicians did she receive her morphine as ordered. Even then, her morphine dose would be administered late, leaving her in pain during the intermediate time interval.

When I visited her at the nursing home, a mutual friend informed me that although she was in extreme pain, she did not want to "upset" anybody and was reluctant to inform her physician of her pain. Her prescription regimen was for oxycodone every eight hours PRN, and she would have to ask her nurse for the pain medication every time. With this regimen, she experienced pain during the entire 3-4 hours prior to her next dose. I told her that I would speak to her physician to review her pain medication. At first, she was extremely anxious because she feared she would be perceived as a difficult patient. Later, however, she thanked me. After communicating with her clinicians, she was ordered a slightly lower dose of oxycodone every four hours ATC. This helped better control her pain and contribute to a better quality of life during the post surgical period.

In both my personal and professional experience, it is extremely common that patients are prescribed generic medication regimens that are not individualized for their specific needs compounded by an ineffective follow-through by practitioners for optimizing patient pharmacotherapy. My personal friends and family have been affected by this type of healthcare standard that currently exists. As clinicians, we need to transform the subjective and generic dynamic in which we select, prescribe and monitor medication regimens, especially for our elderly patients, and create a scientific standard founded on objectifying their pharmacotherapy.

If my friend had undergone clinically relevant genetic testing, especially cytochrome P450 (CYP450) 2D6 testing, her team could have obtained objective data to assist in optimizing her pain medication regimen at the initiation of treatment. As a clinician, I wanted to know her CYP2D6 metabolism prior to making my recommendations to her team. In addition, we need to create the environment, communication tools and time needed to help enhance communication with our patients. We need to take into account the various psycho-social and biological factors that can impede our ability to individualize treatment. My friend could have been assigned a regimen that was individualized for her. Instead, she endured weeks of pain until her final regimen adjustment. This situation was worsened by a breakdown in communication and follow through between my friend and those responsible for her care. We need to improve our patients' pharmacotherapy and safety by implementing these tools as the standard of care, especially in our elderly population.

Fortunately, my friend has since recovered from her post surgical pain and is doing well.

Posted in: Patient/Clinician Relationship

Wednesday, 03/18/2009 at 3:03 PM

How Frequently Should I Test My Patients?

AbacusAs the president of a clinical laboratory, I cannot answer this question for you. There are no published guidelines for urine drug testing frequency from any society, academy or association that I am aware of. As a physician, I can tell you about my experiences, the experiences of my colleagues and published research and recommendations.

I practiced pain medicine in a pain & addiction clinic, so most of my chronic pain patients suffered from the disease of addiction. So as not to appear as being biased (which we were often accused of), we tested every patient at every visit. Our three-strikes-and-you’re-out policy seemed to work well to keep motivated patients in the program, and refer others to a higher level of care. This policy of frequent testing allowed us to address relapse issues early, helped to build trust, and confirmed adherence. All of this improved the care that we delivered to our patients. What I learned through this process is to always give my patients the benefit of the doubt, as long as there’s a UDT collected to corroborate the history.

A colleague of mine uses a popular protocol for testing that stratifies patients based upon risk of misuse or addiction. Patients are placed into low, medium or high risk categories and tested accordingly (i.e., low risk - annually, medium risk - quarterly, high risk - every visit or 1-2 months). This strategy allows for early identification of patients who may be at risk of misuse or addiction and limits potentially unnecessary testing for low risk patients who are making progress in treatment.

Recommendations from research articles and pain medicine publications vary widely in specifics. Of those that recommend testing, some suggest testing every patient at every visit1, while others suggest testing as a response to aberrant behavior.2 There is research that indicates urine drug testing in combination with other clinical observations provide more insight into pharmacotherapy than either used separately.3

Until progress is made in guidelines for monitoring pharmacotherapy, it is up to each clinician to determine an appropriate testing protocol for their practice and their patients. I'd like to hear from you about how you determine testing frequency to monitor pharmacotherapy for your patients and what your experience has been (positive and negative). You can comment on this post or send me an email.

  1. Katz NP, Managing Chronic Pain with Opioids in Primary Care. Inflexxion Health Series, 2007.
  2. Hammett-Stabler CA, Webster LR, A Clinical Guide to Urine Drug Testing: Augmenting Pain Management and Enhancing Patient Care. UMDMJ–Center for Continuing and Outreach Education, 2008.
  3. Katz NP, et al., Behavioral Monitoring and Urine Toxicology Testing in Patients Receiving Long-Term Opioid Therapy. Anesth Analg 2003;97:1097-102.

Posted in: Drug Testing

Tuesday, 03/10/2009 at 12:18 PM

Why Determining Drug Dose in Urine is a Myth

Pills-on-calendar200 I have had several conversations where I have been asked if urine levels depict the dose and frequency of drugs detected in the urine. There is concern for both prescription medications (prescribed by that clinician or prescribed by other clinicians) and non-prescribed drugs. Clinicians need and want to determine a patient's adherence and extent of patient adherence. We also want to know if the medication, dose, and frequency prescribed is the best combination for our patient. We need to know how the patient is taking their medication so we can prescribe or adjust their medication accordingly. If a person takes too much or is not taking their medication, they can become ill either because of the medication or because the condition is not being treated appropriately. For these reasons and many more, it is understandable that clinicians are looking for a measurement that tells them specifically the drug dose and frequency that a patient is taking. Unfortunately, drug dose cannot be determined in a urine specimen. The only way you can know exact oral dosage and frequency is if you administer each dose to that patient.

Anne Nafziger, MD, MHS, PhD and Joe Bertino, Jr., PharmD, FCP, two clinicians who both have over 20 years of experience in drug development, clinical pharmacology, and clinical research and are also authors of the UDM: Opioids handbook, have published an exceptional article titled "Utility and Application of Urine Drug Testing in Chronic Pain Management With Opioids" in the January 2009 issue of the Clinical Journal of Pain. The article specifically describes the inability to determine oral drug dose in urine. One primary reason is genetic variations among people. A patient's genetic profile contributes to the rate and extent of ADME (absorption, distribution, metabolism, excretion). The genetic makeup of individuals is unique and therefore drug ADME is unique to that person. The article also states that in addition to differences between individuals, ADME may vary within a single person on a day to day basis. Due to these facts among others covered in the article, the authors state "...without blood concentration data, evaluating quantity of excreted parent drug in urine will not provide unequivocal evidence of patient ...(adherence) with recommended dosing."

So where do we go from here? Ultimately the goal is give our patients optimal pharmacotherapy. Currently, in the clinician-patient relationship, there is information we may collect and analyze to assist in assessing patient adherence. To move even closer to our goal, we need to utilize new tools and state-of-the-art technology. The motivation to write the UDM:Opioids handbook stemmed from the need for clinicians to obtain this information. Because UDM is a comprehensive monitoring strategy, it can provide more clinically relevant information than strictly knowing if the patient is taking the exact dose prescribed at the exact frequency prescribed. This will help shift the focus from drug dose to drug efficacy, and that is what will truly enhance our patients' treatment outcomes.

Posted in: Misconceptions


Welcome to UDM Solutions, the companion blog for the Urine Drug Monitoring: Opioids handbook. Everyone involved in the creation of this handbook is excited about the launch of this new site and the important topics to be covered.

When we were planning the companion site, we thought a blog would be a great way to get readers involved in some of the new ideas presented in the handbook. UDM as defined in the handbook is a comprehensive strategy for monitoring pharmacotherapy. There are many ideas and techniques being integrated to form the complete strategy, and there are many ways to bring them together in a way that is specific to your needs. This blog will provide a forum for the authors to elaborate on UDM and for readers to contribute to the discussion.

To give you an idea of what UDM is about and what you can anticipate reading on this blog, here is a quote from page 8 in the handbook that provides a very basic definition of the UDM strategy.

Urine Drug Monitoring (UDM) is an objective patient-specific pharmacotherapeutic monitoring strategy which logically combines practices and procedures employed in clinical drug trials with current prescribing practices. UDM is a single solution comprised of many complementary parts. Each component scientifically addresses a necessary piece of the drug monitoring equation.

The components of UDM are:

  • Laboratory Diagnostics
  • Clinical Pharmacology
  • Pharmacogenomics and Pharmacogenetics
  • Patient Assessment
  • Medical Informatics

Thanks for visiting this site. We look forward to hearing from you and responding to your comments in the posts ahead.

Posted in: UDM Handbook

Urine Drug Monitoring: Opioids

Urine Drug Monitoring: Opioids

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UDMSolutions is the companion website for the Urine Drug Monitoring: Opioids handbook. The Urine Drug Monitoring (UDM) strategy presents new concepts and new challenges to the way clinicians scrutinize patient pharmacotherapy. We cover the latest developments impacting pharmacotherapy as they relate to UDM and encourage discussion about solutions.

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Clinical Urine Drug Monitoring Laboratory