The ABCs of Pain Management

The ABCs of Pain Management
A World of Pain The ABCs of Pain Management Paul Martin MD Asheville Addiction Consultants

Objective Optimal utilization of medication to improve patient’s function while minimizing untoward consequences to the patient, the patient’s family and the community

Workshop Agenda Demographics and Neurobiology
Addiction and assumptions How to think about pain patients What to do before starting pain tx Risk stratify, stages of pain tx, opioid tx prep Medication pharmacology Functional pharmacology

PAIN Chronic pain alone affects approximately 100 million U.S. adults over the age of 18, estimated to be as high as 43% of the adult population This likely to increase as population ages 30% of surgeries result in chronic pain Greater than combination of heart disease, diabetes, CA, stroke

Pain Can Be Acute or Chronic
Acute Pain Chronic Pain < 3 Months ≥ 3-6 Months Usually obvious tissue damage Pain resolves upon healing Protective function Pain lasts for 3 months or more Pain beyond expected period of healing No protective function 10/12 text SP We all hear about acute and chronic pain but what do we mean by these terms? Acute, as you can see from she slide, is usually pain that is from an obvious source, resolves as the tissue damage resolves and is seen as protective in function. Chronic pain on the other hand is pain that has been present for at least 3 months, does not necessarily correlate with tissue damage, has lasted longer than clinically expected and eventually has no protective function. How, why and in whom acute pain transitions into chronic pain is under intense study, with many opinions as to the mechanism for this transition. At this point it looks most like a variety of neuroimmune modulators that are acting in the periphery and centrally that lead to chronic pain. What is well known is that, once the transition to chronic pain has occurred, then the ongoing pain is reinforced as a disease unto itself. It does not depend on continued tissue damage, it is self supporting and progressive. “Chronic pain can be a disease in its own right” IOM Report on Pain, 2011 1. Cole. Hosp Physician. 2002;38:23-30. 2. Turk, DC, Okifuji A. J Consult Clin Psychol 2002;70(3): 3. Chapman CR, Stillman M: Pathological Pain, Handbook of Perception: Pain and Touch. Edited by Krueger L. New York, Academic Press, 1996, pp 4. Kehlet et al. Lancet 2006; 367:

Pain Physiology

Pathophysiology guides selection of optimal pharmacologic intervention
This slide is a bit busy but it nicely pulls apart the different categories of chronic pain. Nociceptive pain, seen on the left, is the classic pain we all understand from our own experiences on a daily basis. This is the pain that comes from tissue damage of some type. In nociceptive pain the nervous system is intact, doing what it is supposed to be doing and nothing more. It has a clearly protective function, helping us stay safe and informed about our surroundings. This is the most common acute pain. Nociceptive pain also occurs most commonly in chronic pain. It is still the system at work in Rheumatoid or Osteo arthritis. It is commonly the largest contributor to chronic low back pain. It is involved in most chronic pain conditions. The quality of this pain is commonly aching or throbbing. It can be sharp at times. Neuropathic pain is pain caused by damage to, or dysfunction of, the nervous system. This is most commonly seen in post herpetic neuralgia (PHN) and diabetic peripheral neuropathic pain (DPNP). Other chronic conditions such as HIV, post stroke pain, spinal cord injury, phantom limb pain, complex regional pain syndrome (CRPS) or chemotherapy induced pain. This pain is harder to localize and tends to be more burning and electrical. It also has the capacity to show up as allodynia. Allodynia is the presence of severe pain caused by a nonpainful stimuli (such as the severe pain felt just touching the skin of a CRPS patient). Sensory Hypersensitivity is the pain of a nervous system that has become sensitized to pain inputs. This is at times referred to as “wind-up pain” or “central sensitization”. This type of pain usually follows chronic pain inputs that, due to neuroplasticity, change and enhance the CNS’s neurochemical response to pain. This type of pain follows clear neurochemical changes and at times even anatomical changes caused by chronic pain. This type of pain in particular is why pain becomes a disease.

Central Sensitization Sensory Hypersensitivity
Neurophysiologic adaption to chronic pain inputs Neuroplasticity Spinal cord and brain both adapt. Wide dynamic range interneurons, glial cells, NMDA receptor Can occur independently Fibromyalgia, CRPS, IBS, IC Enhanced by stressors, emotional and physical Can co-occur with any chronic pain input How does this occur? How are we to understand this? So what is central sensitization? As noted briefly in the last slide this is a very important pain entity, the core to pain being a disease unto itself. There is substantial research in animals and humans that documents the neurophysiologic changes occurring due to chronic pain inputs. We have all heard about neuroplasticity, the capacity for the brain to continue to change in response to the environment. Pain is a hall mark disease model for neuroplasticity, with a large number of changes in both the spinal cord and brain that occur with ongoing pain inputs. Research indicates that the spinal cord and brain both adapt. In the spinal cord there are cells between the first and second order neuron called wide dynamic range neuron that are part of the pain modulating system. Following chronic pain inputs they that actually begin to enhance the reception and transmission of pain to the brain. In addition there are changes in opioid receptors and glial cell function at the level of the cord. In the brain there are so many sites of potential sensitization that it would take days of lectures to present. These changes are too numerous to discuss but involve changes in glial cell function, NMDA receptors, opioid receptors and more. These changes can lead to independent pain diseases such as fibromyalgia, Complex regional pain syndrome, interstitial cystitis, irrritable bowel and others. We also know that stress increases the release of activating neuromodulators and these interact with this central sensitization to further enhance pain levels. These stressors can be emotional or physical, this leading to confusion clinically. The practitioner can be left with the belief that the stressors are the cause of the pain rather than a factor that stimulates the response to pain. Treating the stressors will still improve pain response though the stressor is not the central etiology of the pain. One of the other very confusing aspects central sensitization is that it is co-occuring with other chronic pain conditions. It becomes a part of the pain picture of other more mechanical pain generators.

Patients with Chronic Pain Often Present with More Than One Type of Pathophysiology
• Fibromyalgia • Irritable Bowel Syndrome • Functional Dyspepsia • Interstitial Cystitis • Neck & Back Pain (without structural pathology) • Myofascial Pain (TMJ) • Pelvic Pain Syndrome • Restless Leg Syndrome • Headaches • Complex Regional Pain Syndrome • Osteoarthritis • Rheumatoid Arthritis • Tendonitis, Bursitis • Ankylosing Spondilitis • Gout • Inflammatory Myositis • Sjogren’s Syndrome • Cushing’s Disease • Tumor-related nociceptive pain • Neck & Back Pain with structural pathology • Sickle-cell Disease • Inflammatory Bowel Disease • Postherpetic neuralgia • Diabetic Peripheral Neuropathy • Sciatica / Stenosis • Entrapment Syndromes • Spinal Cord Injury Pain • Tumor-related neuropathy • Chemotherapy-induced neuropathy • Small fiber neuropathy • Post-Stroke Pain • MS Pain This diagram illustrates this concept best. I like this as a Venn diagram because it represents more accurately the three types of pain and how they relate clinically. It is believed that many patients with chronic pain have more than one type of pathophysiology contributing to their pain. Even though we can identify a pain pathology as having a primary physiologic pain type there is commonly overlap of other pain physiologies. There are not just comorbid pain conditions (like low back pain and fibromyalgia), but syndromes that are causative of each other (spinal pain with a radiculopathy). The most under diagnosed and hard to determine is the level of “hypersensitivity” that is contributing to a chronic pain of another type. How much of low back pain is driven by a central sensitization? This could rise to the level of fibromyalgia and full body pain following a period of chronic back pain, or the sensory hypersensitivity could just augment the low back pain alone. I believe these “mixed pain states” are very common and as clinicians we need to consider these when we are confused about the level of pain reported by individuals. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2-S15.; Dworkin 2011

Psychiatry and Pain

Chronic Pain Partners Sleep disorders Substance Use Disorders
Depression/Anxiety PTSD Bipolar Disorders Personality Disorders

Mood Disorders in Pain Depression rates in USA population
5% current, 9.5 % yearly, 17% lifetime Depression rates in pain 30-54% current, up to 65-80% lifetime Increased suicidal thoughts in depressed pain patients, up to 3 fold in CPP. Anxiety rates in USA population % yearly Anxiety rates in pain Overall prevalence in pain ranges from 16.5% to 50% Fishbain 1999, Tang 2006, Raison 2009, Bair 2004, Knaster 2012

Relative Prevalence of Misuse, Abuse, and Addiction
Total Pain Population Addiction CORE POINT: So, before we go further into talking about problematic behaviors, it is important to pause…take a deep breath and put these problematic behaviors or patients in perspective: We all tend to remember the worrisome or aggravating or infuriating patients…but as already stated… the majority (generally the large majority) of patients who are prescribed opioids for chronic pain use them appropriately without problematic behavior. Evidence indicates it is a small percentage of patients who demonstrate the persistent, dramatic problems associated with out-and-out addiction to these medications. In between, however, there may be a not insignificant minority of patients who misuse or even abuse their medications. Obviously, all of these aberrant medication behaviors are concerning and need to be addressed but this perspective reinforces the need to not overreact and overly limit access to medications that may proof useful and safe for many individuals. Webster LR, Webster RM. Pain Med. 2005;6(6): 15 15

SUBSTANCE ABUSE EPIDEMIOLOGY
Lifetime prevalence in USA 16.7%, with ETOH at 13.5% and other drug use at 7% Prevalence in pain patients is quite varied, % current and 23-41% lifetime. Most commonly cited range is 4-26%. Some ways to predict and contain this risk There are ways to predict and contain this risk to some degree, which we will detail in later modules. Previous notes 51% Americans >12 y/o use ETOH, only 6.7% are heavy drinkers (5 drinks on 5 days in last 30 days) SAMHSA 2002 12-15% ETOH uses are dependent (Anthony 1994 and SAMHSA 2002) COMORBID substance use was 32.6% of heavy drinkers in last 30 days, 16.6% of binge drinkers in last 30 days (binge is 5 drinks one day last 30 days), 5.8% non binge drinkers and 3.6% nondrinkers. (SAMHSA 2002) Any mental disorder had lifetime prevalence of 29% (22% for ETOH and 15% for all other drugs). The most common comorbid condition was affective disorder. (Rosenthal 1995, Fishbain 1999) Fishbain 1999 shows cannabis 6.2% and cocaine 2.2% at admission to clinic. Numbers may be off due to knowing they are being admitted, half life of meds. Rafii 1990 showed 12.5% for MRJ and cocaine total All ETOH dependent have 37% comorbid psychiatric disease. All other non ETOH have 53% MI. This is in contrast to the 5.3% of American non ETOH use dependence life time Alcohol = 13.5%, Drugs = 7% (ECA Study) Personality disorders with substance abuse. In non CPP population the substance users have PD that are borderline (43%) and antisocial (21%). Brown 1996, Cowan 2003, Michna 2004, ECA, Sehgal 2012,

Substance Related Disorders
Pharmacological indicators Tolerance withdrawal Impaired control Greater amount and longer use Unable to quit Time to obtain extensive Craving Social impairment Role failure Use with known social harm Social loss due to use Risky use Use in spite of physical danger Use with continued psych/social harm These are the main categories needed to make a diagnosis in DSM 5. this is similar to the DSM 4 in many ways. Looking at the first 2 and you can see that this is a very easy hurdle to make for “mild” Substance Related Disorder in DSM 5 or the previous dx of “abuse” in DSM 4. . Much of the research into SUD in pain has used this definition, making the outcome skewed in the direction of higher levels of addiction in the pain population than likely appropriate.

CHANGING DEFINITIONS DSM IV DSM V
Abuse defined as 2 elements to meet criteria. Dependence as 3 elements to meet criteria. DSM V Substance Use Disorders, no abuse vs dependence Mild (2-3), Moderate (4-5) Severe (6 and more) Research impact of DSM IV and V criteria

Genetics Twin studies showing 40-70% genetic contribution (ETOH 50%, cocaine 60% and opioids 70%). 4-8 fold increased risk with first degree relative with SUD 1500 genes linked Ho MK, Goldman D, Heinz A, et al. Breaking barriers in the genomics and pharmacogenetics of drug addiction. Clinical Pharmacology and Therapeutics. 2010;88(6):779–791. 3.1. Genetic Links to Dependence Addiction is a complex disease that is multifactorial and polygenic, thus it does not follow a clear Mendelian pattern of gene expression. Unlike disorders such as Down’s syndrome, no single gene has been identified that predisposes individuals to develop addictive behaviours. However, genetic background is believed to influence addiction liability with mutations in certain genes believed to increase an individual’s vulnerability to addictive behaviours should they engage in drug use (see [120]). Twin and adoption studies indicate the heritability of genes that predispose an individual to becoming addicted ranges from 40% to 70% (alcohol: 50%, cocaine 60%, and opiates 70%) [121]. That is up to 70% of the risk for addictive behaviours can be attributed to heritable influences, with a 4–8-fold increase in the risk of developing an addictive behaviour if a first-degree relative has a substance abuse disorder (see [122]). To date 1,500 genes have been linked to an “addiction” phenotype in humans [123] which can further be classified as those related to the initial stages of experimentation, those related to neuroadaptations following continued exposure, and those that influence outcome including the age of onset and patterns of use. The influence of genetic background over addiction appears additive; the more mutations an individual has, the greater their vulnerability to becoming addicted with different genes contributing to addictive behaviours in different individuals is (see [124]). However environment may also exert considerable influence over the development of addiction, which is further confounded by gene-environment interactions [125]. Many psychiatric disorders including depression, stress, and anxiety coexist with substance abuse disorders, as such heritable factors that influence these disorders may be perpetuated by adverse environmental exposures which may act as a trigger to activate a genetic predisposition and influence behavioural outcome, that is, it increases the risk of substance use (see [122]). Ho MK, Goldman D, Heinz A, et al 2010

Why Are We Here?

National Overdose Deaths Number of Deaths from Opioid Drugs
National Overdose Deaths—Number of Deaths from Opioid Drugs. The figure above is a bar chart showing the total number of U.S. overdose deaths involving opioid drugs from 2002 to Included in this number are opioid analgesics, along with heroin and illicit synthetic opioids. The chart is overlayed by a line graph showing the number of deaths of females and males. From 2002 to 2015 there was a 2.8-fold increase in the total number of deaths. Source: National Center for Health Statistics, CDC Wonder

As heroin use has increased, so have heroin-related overdose deaths:
Heroin-related overdose deaths have more than quadrupled since 2010. From 2014 to 2015, heroin overdose death rates increased by 20.6%, with nearly 13,000 people dying in 2015. In 2015, males aged had the highest heroin death rate at 13.2 per 100,000, which was an increase of 22.2% from 2014. Increased availability, relatively low price (compared to prescription opioids), and high purity of heroin in the U.S. also have been identified as possible factors in the rising rate of heroin use. According to data from the U.S. Drug Enforcement Administration, the amounts of heroin confiscated each year at the southwest border of the United States were approximately ≤500 kg during 2000–2008. This amount quadrupled to 2,196 kg in 2013. References Centers for Disease Control and Prevention. Vital Signs: Today’s Heroin Epidemic – More People at Risk, Multiple Drugs Abused. MMWR 2015. Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep. ePub: 16 December DOI: Compton WM, Jones CM, and Baldwin GT. Understanding the Relationship between Prescription Opioid and Heroin Abuse. NEJM. CDC Rudd 2016

Opioid involvement in benzodiazepine overdose
National Overdose Deaths—Number of Deaths from Benzodiazepines, with and without opioids. The benzodiazepines from 2002 to 2015, with the red line representing the number of benzodiazepine deaths that also involved opioids, and the purple line representing benzodiazepine deaths that did not involve opioids. From , benzodiazepine deaths involving opioids increased two fold more than those not involving opioids. Source: National Center for Health Statistics, CDC Wonder

Fig 2 Unadjusted incidence of opioid overdose for patients using opioids with or without benzodiazepines in stratified by intermittent v chronic opioid use and concurrent benzodiazepine/opioid use. BMJ 2017; 356 doi: (Published 14 March 2017) Cite this as: BMJ 2017;356:j760 Fig 2 Unadjusted incidence of opioid overdose for patients using opioids with or without benzodiazepines in stratified by intermittent v chronic opioid use and concurrent benzodiazepine/opioid use – emergency room or hospitalization. Eric Sun, MD, PhD, an assistant professor of anesthesiology, perioperative, and pain medicine at Stanford University in California, and colleagues collected data on 315,428 privately-insured patients, aged 18 to 64, who were prescribed an opioid between 2001 and 2013. Eric C Sun et al. BMJ 2017;356:bmj.j760 ©2017 by British Medical Journal Publishing Group

PAIN CLINIC PATIENTS -80% of CPP are prescribed low doses (<100 mg morphine equivalent dose per day) by a single practitioner and they account for only 20% of all prescription drug overdoses. -10% of patients are prescribed high doses (≥100 mg morphine equivalent dose per day) of opioids by single prescribers and they account for 40% of prescription opioid overdoses. -The remaining 10% seek care from multiple doctors, are prescribed high daily doses, and account for 40% of opioid overdoses. So can we figure out who those at risk actually are? Who are these people dying from these meds? The most simple and clear graphic I have found that parses out the groups most at risk is this one. 80% of CPP are prescribed low doses (<100 mg morphine equivalent dose per day) by a single practitioner and they account for only 20% of all prescription drug overdoses. 10% of patients are prescribed high doses (≥100 mg morphine equivalent dose per day) of opioids by single prescribers and they account for 40% of prescription opioid overdoses. The remaining 10% seek care from multiple doctors, are prescribed high daily doses, and account for 40% of opioid overdoses.

DRUG SUPPLY NMU -70% From friend/relative in some fashion (free + bought/stolen) -65%of all meds nonmedical are from 1 MD -5% of all nonmedical are Drug dealer/stranger -3% of all nonmedical are More Than 1 MD SO the supply problem is difficult, friends primarily and that from appropriate tx 70% From friend/relative in some fashion (free + bought/stolen) 65%of all meds nonmedical are from 1 MD {45% of FREE is 1 MD (56% free is 80% 1MD) + 20% as 1MD} 5% of all nonmedical are Drug dealer/stranger 3% of all nonmedical are More Than 1 MD

Approach to Pain Patient

International Association for the Study of Pain
"Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."

Constant aversive message that your body is damaged or being harmed.
SOMATIC REALITY Constant aversive message that your body is damaged or being harmed. No other medical condition like it due to Persistence Intrusiveness Behavior change unavoidable moment to moment Self perpetuating and self enhancing Constant sensory input implying risk or presence of ongoing bodily damage.

FELT SENSE OF CONTROL Central need for ongoing function
A primary force for keeping egos intact Pain is the antithesis of “felt sense of control” Taunting, distracting, limiting behavior, mood modifying

Maslow’s Hierarchy of Needs
Health is base Abandonment of higher level needs Dysfunctional behaviors Normal to be struggling for control Regression predictable Maslow and Hierarcy of Needs TRYING TO GIVE A SENSE OF WHY PAIN PATIENTS MAY HAVE BAD BEHAVIORS….. A system that is based on building the next level only after you have succeeded at the previous level. Physiology (HEALTH) is at the base. Health is the base on which all other things rest. If you don’t have that then the upper levels, such as safety, belonging, esteem and finally self actualization are abandoned. You won’t care as much about safety, belonging to a group, how you appear to others, you will just want your health under control. “I just want to get some control of this pain” leads to behaviors that appear dysfunctional to the outside world and but make sense to the person committing them in the name of control. THEY ARE TRYING TO REBUILD THE FOUNDATION TO THEIR WORLD, and will do what feels appropriate at the time. The person no longer cares in the same way about being liked by the MD, the nurses, the pharmacist. The regaining of some control is primary. Regression….. All of us in pain would regress to some degree. No personality predicts chronic pain, we would all go through these changes

Basic Problem Personality based Emotional dysregulation
Feels personal Not about you, same with others predictable Emotional dysregulation Poor affective constancy Practitioners emotional response Filling in missing pieces Don’t’ believe everything you think So all of that was the set up, and now, at the core of this is that it is Personality based this is about the patient, it is their structure, it is not about you, feels personal but they do this particlar thing with everyone, NOT JUST YOU they will not be substantially changed by your intervention. LET ME GIVE AN EXAMPLE…...is there something about your PARTNER THAT YOU DON’T LIKE? It happens over and over and it still keeps coming up? In the same way there are things about you your partner does not like, things you have even tried to change or work on. For only 99% of the people these things don’t change substantially, even with GREAT EFFORT WHY would you think you patient is going to change substantially, at core, by your interventions? They are still going to be the same basic person. This can seem HOPELESS but actually it just makes them predicatable, you know what you have. You just need to add it to the formula of your treatment. EMOTIONAL dysregulation. the worst of the difficult patients have poor emotional regulation, they tend to be more mood labile, irritable They tend to be filled with the feelings of the moment, LEADING TO poor AFFECTIVE CONSTANCE. NOT TRYING TO LIE TO YOU, JUST CAN’T KEEP THE PROMISE they made yesterday when they felt differently. ------EXAMPLE OF 7 Y/O WITH CHOCLATE PRACTITIONERS RESPONSE adds to the picture. when you see someone doing these things and DON’T KNOW WHY, YOU WILL FILL IN THE MISSING PIECES. Normal human behavior to fill in missing data with stories, things that make sense to you personally, DIFFERENT FROM PRACTITIONER TO PRACTITIONER DEPENDING ON THE PERSONALITY OF THE PRACTITIONER. You are part of the mix, how you respond will have a very large impact on the behavior of your patient. My undelying truism about this is DON’T BELIEVE EVERYTHING YOU THINK. DONT FORGET that you need to get all the facts, that being curious about what is going on will serve you better than feeling you are the ONLY ONE THAT IS RIGHT.

Normal Psychological Structure 101
Everyone makes mistakes Everyone has difficult personality features Everyone has hidden behaviors Everyone has some level of anxiety that shapes behavior Everyone has aggression, direct or indirect Everyone feels two ways about nearly everything they do, ambivalence Everyone tends to regress, get more primitive, when stressed

Optimal Approach Avoid playing “gotcha” Be curious rather than right
Patient hiding in response Be curious rather than right Educating in response Share control Power mutual, not struggled with Establish clear limits Trust and no surprises yet responsible So how do we roll these items into an optimal approach to these difficult patients? We know that patients worry that we will not believe them when they discuss their pain, or that we will not understand when they use their meds too quickly during a pain flare, or fear we will judge them when they are not functioning well. They fear their own mistakes, hidden behaviors, and difficult parts of their personalities. If we, as practitioners, come from a place of “catching” them in these normal behaviors we risk setting up a dynamic that is counterproductive to our intentions. If we take on the role of playing “gotcha” they will naturally (just as we would in that same situation) take the role of “hiding”. In addition, if your task is to catch them at something then you are done with your task once you have caught them. You are not treating them, you are “catching” them. Commonly the “treatment” stops after the “catch”. At that point the patient looses, it feels like you win, but there is no treatment and the situation starts again somewhere else. In the coming ACO environment this will be a small catastrophe since the patient will not be able to be discharged from your groups responsibility or bottom line. This has been a workable and in some ways appropriate approach in the past but in the likely future of medicine we have to find a different way out of this conundrum. I suggest a different approach, which some of you already apply most likely. I suggest, and as much as possible I practice, an approach that is “curious not right” (as much as I can). It is easy to be right, it just requires ignoring the input from other people, other inconvenient facts, other viewpoints…. and you can win by just getting louder and larger. Just look at politics in America these days. It is much harder to be curious, to ask more questions, to actually ask to be taught something you may not know or fully understand. But this moves the dynamic from a response all about hiding to a response more about educating the one that is curious. It naturally opens the channel we need open to get the information required for us to make an optimal medical decision. What may be surprising to some is that I am not just being touchy/feely. I am not just trying to “understand” everyone (though that happens more readily and is helpful). I am not some simple bleeding heart or only a patient advocate. My purpose is purely to get the information I need to prepare the optimal path of treatment in a complex case. I am being TACTICAL, some may even say manipulative. But I do this to optimize treatment and my only purpose is the patients’ long-term function. Another stance, derivative of another axiom, is to share control. Paraphrasing, “the best way to gain power is to give it away”. Share control and power. If the dynamic is to keep power for yourself then the other person in the relationship will tend to fight you so as to retain some power. This fight, natural aggression, can be passive or active, both of which can be surprising. A derivative of this is “make it about them”. “My whole intention is for you to have better function. I am not doing any of this for me”. The final leg of this approach is to have clear limits, with plenty of warning about when they are coming close to them. I use a football field metaphor that goes like this……. Working with this group of patients is time consuming and challenging. There ware many ways we tend to protect ourselves as humans, most of them due to reasonable fears we as practitioners feel. We fear for the time used that we don’t have, the potential we are being lied to, the concern about opioids and safety, all to name a few. Out of our fears come defenses, again all natural, some that are less helpful than others when applied to the clinical dynamic when treating pain. We know that patients worry that we will not believe them when they discuss their pain, or that we will not understand when they use their meds too quickly during a pain flare, or fear we will judge them when they are not functioning well. If we, as practitioners, come from a place of “catching” them in these behaviors we risk setting up a dynamic that is counterproductive to our intentions. We we have the role of playing “gotcha” they will naturally (just as we would in that same situation) take the role of “hiding”. In addition, if your task is to catch them at something then you are done with your task once you have caught them. You are not treating them, you are “catching” them. Commonly the “treatment” stops after the “catch”. At that point the patient looses, it feels like you win, but there is no treatment and the situation starts again somewhere else. In the coming ACO environment this will be a small catastrophe since the patient will not be able to be discharged from your groups responsibility or bottom line. MORE CONTENT TO COME, iterative of the above.

Case Discussion: Applying Safe Opioid Strategies in Your Clinical Setting
Ok, have some background, now how do we start to think about how to apply some of this to a patient. Lets start with a casses

Case Discussion 42-year-old male with h/o total L hip arthroplasty (THA) presented for 1st time visit with c/o left hip pain One year ago displaced left femoral neck fracture requiring THA with subsequent chronic hip pain Pain managed by his orthopedist initially with oxycodone and more recently with ibuprofen MRI of Lumbar Spine done 1 month ago revealed mild RIGHT foraminal narrowing with intact disks Let’s review a case which will highlight many important issues around the management of chronic pain using long-term opioids. A 42-year-old man with a history of total hip arthroplasty presented for first-time visit with complaints of hip pain. One year ago he had a displaced left femoral neck fracture requiring total hip arthroplasty with subsequent chronic hip pain. His pain was managed by his orthopedist, originally with oxycodone and more recently with ibuprofen. Recent extensive reevaluation of his hip pain was negative. Daniel Alford, MD, MPH 39

Case Continued: Requested that his orthopedist prescribe something stronger like “oxys” for his pain as the ibuprofen was ineffective Told to discuss his pain management with his primary care physician (you) but presented initially to the ER. What would your local Emergency Dept. policy/response likely be? He requested that his orthopedist prescribe something stronger like “Oxys” for his pain, as the ibuprofen was ineffective. He was told to discuss his pain management with his primary care physician (you). He’s been on disability since his hip surgery and lives with his wife and two children. He denies current or history of alcohol, tobacco or drug use. Daniel Alford, MD, MPH 40

Case continued: Meds: Ibuprofen 800 mg TID intermittently
Walks with a limp, uses a cane, vitals normal, 6 ft, 260 lbs Large well-healed scar over the left lateral thigh/hip with no tenderness or warmth over the hip, full range of motion Doesn’t want to return to his orthopedist because “he doesn’t believe that I am still in pain.” Pain 8/10 disturbs sleep/activity Currently, he’s on ibuprofen 800 mg three times per day. He walks with a limp and uses a cane. His vitals are normal. He’s 6 foot, 230 lbs. He has a large, well-healed scar over the left lateral thigh and hip area with no tenderness or warmth over the hip, full range of motion. He doesn’t want to return to his orthopedist, because “he doesn’t believe that I’m still in pain.” Daniel Alford, MD, MPH 41

Initiation of Pain Therapy
Pain Assessment Risk Assessment Psych, SUD, family hx UDS Review NC Controlled Substance Reporting System Informed Consent/ Treatment Agreement Patient education “Trial” of opioids Functional goals Put in the EPIC assists or give web site to them

Case continued: One pain is an aching/throbbing pain over the left hip joint Another pain is a burning sensation over the left lateral thigh Intermittently he has tingling pain that begins in his left lower back and goes down the side of his leg to his foot. Currently, he’s on ibuprofen 800 mg three times per day. He walks with a limp and uses a cane. His vitals are normal. He’s 6 foot, 230 lbs. He has a large, well-healed scar over the left lateral thigh and hip area with no tenderness or warmth over the hip, full range of motion. He doesn’t want to return to his orthopedist, because “he doesn’t believe that I’m still in pain.” Daniel Alford, MD, MPH 43

Case continued: On disability since his hip surgery and lives with his wife and 2 children Largely inactive and wife reports: “kind of mopey”, “ill and irritable much of the time.” Cigarette smoker – 1-2 PPD Denies current or prior history of alcohol or drug abuse (“Just a few beers while watching the tube”) In summary: 42 yo man on disability with chronic hip pain who is requesting “oxycodone”

Case continued: Family History – mother had depression, father & paternal uncle were “stoners” in past Wife is secretary at local high school Second marriage for both He worked construction prior to non-work-related injury Two kids ages 16 and 12 – both of this marriage 16 year old son is “running with wrong crowd”

Case continued: Pain Risk Factors:
Family History – mother had depression, father & paternal uncle were “stoners” in past “Kind of mopey” Smoker / ? alcohol Disability for a year / manual labor job Obesity 16 year old son is “running with wrong crowd” Age

Pathophysiology guides selection of optimal pharmacologic intervention
This slide is a bit busy but it nicely pulls apart the different categories of chronic pain. Nociceptive pain, seen on the left, is the classic pain we all understand from our own experiences on a daily basis. This is the pain that comes from tissue damage of some type. In nociceptive pain the nervous system is intact, doing what it is supposed to be doing and nothing more. It has a clearly protective function, helping us stay safe and informed about our surroundings. This is the most common acute pain. Nociceptive pain also occurs most commonly in chronic pain. It is still the system at work in Rheumatoid or Osteo arthritis. It is commonly the largest contributor to chronic low back pain. It is involved in most chronic pain conditions. The quality of this pain is commonly aching or throbbing. It can be sharp at times. Neuropathic pain is pain caused by damage to, or dysfunction of, the nervous system. This is most commonly seen in post herpetic neuralgia (PHN) and diabetic peripheral neuropathic pain (DPNP). Other chronic conditions such as HIV, post stroke pain, spinal cord injury, phantom limb pain, complex regional pain syndrome (CRPS) or chemotherapy induced pain. This pain is harder to localize and tends to be more burning and electrical. It also has the capacity to show up as allodynia. Allodynia is the presence of severe pain caused by a nonpainful stimuli (such as the severe pain felt just touching the skin of a CRPS patient). Sensory Hypersensitivity is the pain of a nervous system that has become sensitized to pain inputs. This is at times referred to as “wind-up pain” or “central sensitization”. This type of pain usually follows chronic pain inputs that, due to neuroplasticity, change and enhance the CNS’s neurochemical response to pain. This type of pain follows clear neurochemical changes and at times even anatomical changes caused by chronic pain. This type of pain in particular is why pain becomes a disease.

Questions: Do you believe the patient? How confident are you in deciding between “drug seeking” and seeking pain relief? Are opioid analgesics indicated? What else would you want to know or do to help decide? Would you prescribe opioids? At this visit? What other treatment options do you have? Summary: a 42-year-old man on disability with chronic hip pain who is requesting oxycodone. The questions are: is he drug seeking and are opioid analgesics indicated? Daniel Alford, MD, MPH 52

Step Treatment of Pain Diet Exercise Restorative Sleep
Smoking Cessation Our patients BMI = 31.2

Step Treatment of Pain Physical modalities Topical agents Massage
Relaxation exercises Elevation / splints / compression Physical modalities – heat/ice, TENS, accupuncture, dry needling Topical agents - Lidoderm 5% $400/30 OTC 4% - $2 each

Pharmacologic Treatments
Alpha-2-delta ligands, SNRI’S, tricyclics, beta-blockers, antidepressants NE agents, etc. Tramadol, Avoid opioids in Migraine and Fibromyalgia NSAIDS oral Topical Duloxetine Tramadol Opioids last option Alpha-2-delta ligands SNRI’s Tricyclics Anticonvulsants NMDA antagonists Etc Tramadol Opioids last option Once you move into pharmacologic treatments it is helpful to once again consider the type of pan condition you are treating. On the Left of this slide you see nociceptive pain (LINK to nociceptive pain tx). As you know, classically the treatments are NSAIDS. Duloxetine has indications for nociceptive pain related to back and knee and is worth considering. (LIND to duloxatine indications). Tramadol has minimal opioid function, mostly working through serotonin norepinephrine. It has minimal addictive potential. Tapentadol has clear opioid function but also works through norepinephrine. It has less addictive potential clinically. Both of these are unique and tend to be less problematic than opioids relative to abuse. I commonly use them as a half step up the ladder towards regular opioids, avoiding some degree of risk. On the Right you can see some of the pharmacologic options for neuropathic pain (LINK to neuropathic pain tx). These range from agents such as gabapentin all the way to ketamine. Again you see tramadol and tapentadol as mid way options. On the Top you again see many of the same agents used for neuropathic pain. In many ways sensory hypersensitivity (AKA central sensitization) can be considered a special subset of neuropathic pain, thus the same meds are applicable. Noted here is the caveat that most protocols state that opioids should be avoided in headache or fibromyalgia due to the potential for progression of the disease or other unhelpful outcomes.

Assessment of the Pathophysiology of Pain Can Help Guide Appropriate Medication Therapy
Neuropathic Pain and Sensory Hypersensitivity Mild Moderate Severe Nociceptive Pain NSAIDS, Acetaminophen1,2 AEDs, SNRIs, TCAs3,4 <<Presenter: Lecture notes must be read verbatim>> Let’s say you have successfully used the tools to asses the type of pain pathophysiology in a particular patient… So why IS it so important? Because it can help guide rational selection of pharmacologic treatment and a treatment plan that is appropriate and specific for the pain type, the patient, and the treatment goals. Here’s a schematic representation of the nociceptive pain, neuropathic pain, and sensory hypersensitivity (or fibromyalgia-like pain). Pain of any type can be mild, moderate, or severe. Nociceptive pain of various severities can be effectively managed by medications such as NSAIDS or acetaminophen. In contrast, NSAIDs are neither intended nor indicated for the treatment of neuropathic pain or fibromyalgia-like pain (sensory hypersensitivity), and there are no data to suggest that they are efficacious in conditions with this pathophysiology For painful conditions with neuropathic pathophysiology or that of sensory hypersensitivity, the first-line treatment options are antiepileptic drugs (AEDs), serotonin–norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs). AEDs, antiepileptic drugs; SNRIs, serotonin–norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants. Hochberg M et al. Arth Care Res. 2012;64(4): Chou R et al. Ann Intern Med. 2007;147(7): Dworkin RH et al. Pain. 2007;132(3): Attal N et al. Eur J Neurol. 2010;17(9):

Step Treatment of Pain Acetaminophen NSAIDs / COX II
SSRIs/SNRIs Antidepressants Muscle Relaxants Anticonvulsants Steroids

First Level Treatment Non pharmacologic Low risk pharmacology
Diet, PT, graded exercise, stress management, DBT, biofeedback, acupuncture, etc Interventional Low risk pharmacology NSAIDS - nociceptive Adjunctives – neurogenic/hypersensitization AED’s, TCA’s, etc SNRI’s Low level pharmacology NSAIDS, adjunctives, etc make sure you are not contributing to lack of function due to increasing sedation or odd med reaction re eval med reactions at all times mood tx, SNRI’s for dual dx effect, pain and mood both Pain

Tricyclic Antidepressants: Adverse Effects
Commonly reported AEs (generally anticholinergic): dry mouth sedation cognitive changes (concentration, memory, confusion) constipation orthostatic hypotension blurred vision tachycardia urinary retention1,2 Most AEs Amitriptyline Doxepin Imipramine Trazodone* Nortriptyline Desipramine2,3 Adverse effects (AEs) commonly reported with tricyclic antidepressants (TCAs) are anticholinergic effects, which are listed on the left side of the slide. The AEs include sedation, cognitive changes, dry mouth, constipation, orthostatic hypotension, blurred vision, tachycardia, and urinary retention. All TCAs report these AEs in varying degrees of frequency and severity.1,2 The TCA agents listed on the right side of the slide are organized in decreasing order of producing AEs, starting with amitriptyline (most AEs), and continuing with doxepin, imipramine, and nortriptyline, to desipramine (fewest AEs).2,3 Because the TCAs appear to be almost equally efficacious, a commonsense approach for physicians is to start with the agents with the fewest AEs, unless they want to produce a specific “side effect” such as nighttime sedation. 1. Galer BS, Dworkin RH. A Clinical Guide to Neuropathic Pain. Minneapolis, Minn: McGraw-Hill Companies, Inc.; 2000:72-73. 2. Mackin GA. Medical and pharmacologic management of upper extremity neuropathic pain syndromes. J Hand Ther. 1997;10: 3. Tunali D, Jefferson JW, Greist JH. Depression and Antidepressants: A Guide. Madison, Wis: Information Centers, Madison Institute of Medicine; 1999. Fewest AEs 1.Galer BS, Dworkin RH. A Clinical Guide to Neuropathic Pain. McGraw-Hill Companies; 2000. 2. Mackin GA. J Hand Ther. 1997;10: 3. Tunali D et al. Depression and Antidepressants: A Guide. Madison Institute of Medicine; 1999.

Antidepressants SNRI’s Venlafaxine 37.5-300mg (Effexor)
Least NE SNRI’s Venlafaxine mg (Effexor) HTN, norepinephrine at higher doses some pain literature support Duloxetine mg (Cymbalta) Stimulation, norepinephrine at all doses FDA approved for 2 mood and 3 pain conditions Levomilnacipran (Fetzima) mg Most NE of any SNRI, from Milnacipran (Savella) Duloxetine - $22 with Good RX coupon; Venlafaxine – same. Brintellix – no longer available Vortioxetine is a so-called "serotonin modulator and stimulator".[19] It has been shown to possess the following pharmacological actions:[1][20][21] SSRI 5ht1A, strong partial to nearly full agonist NE some Many other 5HT receptors B1 adrenergic and may give SE (check on Meisner’s work with this). Serotonin transporter (SERT) blocker (i.e. serotonin reuptake inhibitor (SRI)) — Ki (binding affinity) = 1.6 nM, IC50 = 5.4 nM Norepinephrine transporter (NET) blocker — Ki = 113 nM 5-HT1A receptor high-efficacy partial agonist/near-full agonist — Ki = 15 nM, IA = 80% 5-HT1B receptor partial agonist — Ki = 33 nM 5-HT1D receptor antagonist — Ki = 54 nM 5-HT3A receptor antagonist — Ki = 3.7 nM 5-HT7 receptor antagonist — Ki = 19 nM Vortioxetine also has affinity for the β1-adrenergic receptor (Ki = 46 nM), though any actions at this site are unlikely to contribute to its therapeutic effects and likely only to contribute to side effects.[20] fetzima Relative to other SNRIs, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine.[5][6][7] To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 10:1, milnacipran = 1:1, and levomilnacipran = 1:2.[5] The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear,[5] but may include improved effectiveness, though also increased side effects.[7][8][6] the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 10:1, milnacipran = 1:1, and levomilnacipran = 1:2.[5] Most NE

Anticonvulsant Drugs and Neuropathic Pain
First Generation Carbamazepine (Carbatrol®, Tegretol®)A and C Phenytoin (Dilantin®)A Valproic acid (Depakene®, Depacon® injection)B Clonazepam (Klonopin®)B PhenobarbitalB Second Generation Gabapentin (Neurontin®)A and C Lamotrigine (Lamictal®)A Levetiracetam (Keppra™)B Oxcarbazepine (Trileptal®)A Tiagabine (Gabitril®)B Topiramate (Topamax®)A Zonisamide (Zonegran®)A Pregabalin (Lyrica®)A and C Anticonvulsant medications have been used in the treatment of neuropathic pain for many years without FDA approval (except for carbamazepine’s indication for trigeminal neuralgia).1,2 These drugs are among the most frequently used treatments for neuropathic pain. This widespread usage is based on the efficacy of carbamazepine in trigeminal neuralgia and on the results of several studies of carbamazepine and phenytoin in patients with painful diabetic neuropathy conducted in the 1960s and 1970s.2 More recently, well-controlled double-blind trials of gabapentin have established the efficacy of this second-generation aniticonvulsant in treating postherpetic neuralgia and painful diabetic neuropathy.2 The first-generation anticonvulsant drugs sometimes provoke serious side effects and drug-drug interactions that do not occur among all second-generation anticonvulsants.2 The slide lists anticonvulsants that have been reviewed in the medical literature as potential treatments for neuropathic pain. The superscript A indicates that published randomized controlled trials provide evidence of efficacy in the treatment of one or more neuropathic pain syndromes; the superscript B reflects clinical anecdotes and/or published case series suggesting that the drug may be effective in these patients. McQuay H, Carroll D, Jadad AR, Wiffen P, Moore A. Anticonvulsant drugs for management of pain: a systematic review. BMJ. 1995;311: 2. Ross EL. The evolving role of antiepileptic drugs in treating neuropathic pain. Neurology. 2000;55(suppl 1):S41-S46. GABAPENTIN Most common first line treatment for neuropathic pain. Indication for Postherpetic Neuralgia. Studies showing efficacy in PHN and diabetic neuropathy (Backonja 1998, Rowbotham 1998) Mechanism of action stated as “unknown”, but evidence supports the following. Binds a subunit of voltage-dependent Ca++ channel Increases GABA in the brain (increased glutamate synthesis?) Partially inhibits glutamate production enzymatically (Upton 1994, Chadwick 1994, Petroff 1996, Goldlust 1995) LAMICTAL Sodium channel blocker with inhibition of glutamate release Effective in trigeminal neuralgia Effective in trial treating HIV or diabetic related neuropathy Some mixed results in recent study (McCleane 1999 and 2000, Canavero 1997, Zakrxewska 1997, Lunardi 1997, Simpson 2000, Eisenberg 1998) TOPAMAX Action of sodium and calcium blockade and GABA activation Few studies but looks promising Helpful with weight reduction in some Begin 25mg per day, increasing by 25mg per week. Up to mg per day. (Bwaja 1999) GABITRIL GABA activation Promising in animal models Appears helpful in anxiety Sedating and need to start at low doses (2-4mg per day, increasing by same every 5-7 days). Up to 56mg per day. (Tremont-Lukats 2000) “A” randomized controlled trials. “B” anecdotes and/or published case series. “C” FDA approved for pain indication

Case Continued: You get a ROI for old records and you decide against opioids at the initial visit: You continue the ibuprofen, putting him on a running dose of 800 mg tid with food as well as a lidocaine patch to apply to the specific area of greatest pain. You also begin a titration of gabapentin 300 mg up to 1800 mg/day You refer to PT for education and treatment and schedule follow-up in 4 wks. You put him on notice that smoking cessation will be a future goal Back in 2005, the FDA warned that taking nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen increased the risk of having a heart attack or stroke. In July 2015 it took the unusual step of further strengthening this warning. People who have cardiovascular disease, particularly those who recently had a heart attack or cardiac bypass surgery, are at the greatest risk for cardiovascular adverse events associated with NSAIDs. Gabapentin 600 mg TID = $28.00/month.

Case Continued: one month later
He reports using the ibuprofen, the lidocaine patch, and gabapentin but states his pain is unimproved (“I told you it wouldn’t work”). Besides the ibuprofen upset his stomach. He went to PT twice but then stopped: “It made the pain worse.” Plus “I can’t afford the $100 copay” PHQ-9 done today = 9 (Mild Depression) Old records from the surgeon are c/w patient’s report. What other non-narcotic approaches might you take?

1-4 Minimal depression; 5-9 Mild depression; Moderate depression; Moderately severe depression; Severe depression

Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively. When used as a screening tool, further evaluation is recommended when the score is 10 or greater. Using the threshold score of 10, the GAD-7 has a sensitivity of 89% and a specificity of 82% for GAD

Case Continued: one month later
You discontinue the ibuprofen & lidocaine patch and begin meloxicam 15 mg qD You continue the gabapentin 600 mg TID You advise him to do his PT at home – and walk around his neighborhood for 20 minutes a day You begin Trazodone 50 mg QHS Follow up in 2 weeks He follows up and says his sleep is some better but his pain is 10/10 most of the day. Why can’t I just try what worked before?

Initiation of Opioid Therapy

Risk Stratification Prior to Prescribing
Low Risk High Risk Etiology of Pain Clear/Identified Vague/Non-specific Substance Abuse Negative family or personal history Past history but stable recovery Active abuse or addiction Psychiatric History None Few/stable Multiple/unstable Environment Stable/Supportive Resources Unstable/ Few resources Activity Engagement Employed/Active/ Engaged in tx. Unemployed/ Inactive/Med only CSDB One prescriber/Opioids low dose/no bz One prescriber/Moderate dose/Benzos Multiple prescribers/High dose/Benzos/irregularities Long vs short acting opioids Tamper resistant meds Speaker Notes: As noted by the most recent guidelines from the American Pain Society, risk stratification is an integral part of patient selection for chronic opioid therapy.1 The chart presented here demonstrates the different levels of abuse risk based on specific patient characteristics.2 The purpose of the chart is to recommend appropriate monitoring for patients by indicating the healthcare settings that should be involved in patient management based on risk levels.2 References: Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2): Gourlay DL, Heit H, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):

Opioid Risk Tool (ORT) Mark each box that applies Female Male
1. Family Hx of substance abuse Alcohol Illegal drugs Prescription drugs 2. Personal Hx of substance abuse 3. Age between 16 & 45 yrs 4. Hx of preadolescent sexual abuse 5. Psychologic disease ADD, OCD, bipolar, schizophrenia Depression 1 3 On initial visit Prior to opioid therapy 2 3 4 4 3 3 4 4 5 5 0-3: low 4-7: moderate ≥ 8: high 1 1 Pain Med Nov-Dec;6(6): Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Webster LR, Webster RM. Author information Abstract OBJECTIVE: To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain. DESIGN: One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool (ORT). The ORT measured the following risk factors associated in scientific literature with substance abuse: personal and family history of substance abuse; age; history of preadolescent sexual abuse; and certain psychological diseases. Patients received scores of 0-3 (low risk), 4-7 (moderate risk), or >or= 8 (high risk), indicating the probability of their displaying opioid-related aberrant behaviors. All patients were monitored for aberrant behaviors for 12 months after their initial visits. RESULTS: For those patients with a risk category of low, 17 out of 18 (94.4%) did not display an aberrant behavior. For those patients with a risk category of high, 40 out of 44 (90.9%) did display an aberrant behavior. The authors used the c statistic to validate the ORT, because it simultaneously assesses sensitivity and specificity. The ORT displayed excellent discrimination for both the male (c = 0.82) and the female (c = 0.85) prognostic models. CONCLUSION: In a preliminary study, among patients prescribed opioids for chronic pain, the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related, aberrant behaviors. Further studies in a variety of pain and nonpain settings are needed to determine the ORT's universal applicability. 3 2 2 1 1 Scoring Totals: Accessed Jan 2014. Webster LR, et al. Pain Med. 2005;6:

Risk Stratification Prior to Prescribing
Low Risk High Risk Etiology of Pain Clear/Identified Vague/Non-specific Substance Abuse Negative family or personal history Past history but stable recovery Active abuse or addiction Psychiatric History None Few/stable Multiple/unstable Environment Stable/Supportive Resources Unstable/ Few resources Activity Engagement Employed/Active/ Engaged in tx. Unemployed/ Inactive/Med only CSRS One prescriber/Opioids low dose/no bz One prescriber/Moderate dose/Benzos Multiple prescribers/High dose/Benzos/irregularities Long vs short acting opioids Tamper resistant meds

AUDIT - C How often did you have a drink containing alcohol in the past year? How many drinks did you have on a typical day when drinking? How often did you have 6 or more drinks on one occasion in the past year? Positive screen: Women >3, Men >4 Each question 0-4 points. In men a score of 4 or more is considered positive. In women 3 or more is positive. Scores >8 indicates dependence. Scores 4-7 in folks with no prior alcohol treatment: Brief Intervention. >8 (in anyone) or any positive answer in folks with prior treatment should be referred.

Full AUDIT Positive Considered >8
1st 3 Questions constitute AUDIT-C Women >3 Men> 4 = Positive

AUDIT - C Your patient scored a 5 on the AUDIT-C, so the full AUDIT was done which resulted in a 7. With the Full Audit 4-7 calls for Brief Intervention With the Full Audit > 8 should be referred Each question 0-4 points. In men a score of 4 or more is considered positive. In women 3 or more is positive. Scores >8 indicates dependence. Scores 4-7 in folks with no prior alcohol treatment: Brief Intervention. >8 (in anyone) or any positive answer in folks with prior treatment should be referred.

Risk Stratification Based on Risk Assessment, can my practice provide sufficient structure to allow this patient to safely take controlled substances?

Monitoring Individuals on CS
Periodic drug screening Family monitor Pill counts Controlled Substance Reporting System Patient Eval– Analgesia, Activity, Adverse Effects, Aberrant Behavior, Affect (Five A’s) Discussion with therapist

Screening vs Definitive Testing
Liquid chromatography/tandem mass spectrometry

Recent Billed Charges $1,480.30 Millennium Labs
$3, Oaktree Medical Centre $1, Physician Choice Lab Dx – long-term (current) use of other medications, encounter for therapeutic drug monitoring.

How Many Panels? One Panel Fifteen Panels
Saliva fluid samples may be collected under direct supervision without bathroom facilities, More difficult to adulterate, but Short detection time (12 – 24 hours), limited number of drugs available for screening. Hair - Long detection time (3 to 6 months) Easy to handle and store Less susceptible to tampering, limited number of drugs, does not reveal recent use Sweat Tests prospectively, not retrospectively, for one to three weeks Non-invasive collection Relatively tamper-proof adhesive patch, but Limited number of drug tests available Accidental removal during monitoring period Environmental contamination possible before application or after removal Blood - Difficult to adulterate but Short detection time (12 – 24 hours) Invasive collection One Panel Fifteen Panels

How Many Panels? Drug being prescribed Marijuana Cocaine
Amphetamine/Methamphetamine Oxycodone Buprenorphine Methadone Opiates (Morphine, codeine, hydrocodone) Alprazolam (Xanax) / clonazepam (Klonopin) Others based on local drug use/availability No, codeine is NOT a metabolite of hydrocodone

NC Medicaid / Medicare Reimbursement
G0477 – Medicaid old code 80305 (As of January 2017) $13.52 HCPCS G0431 and G0434 were end- dated effective Dec 31, 2015 Providers should select the most appropriate code from the lab section of the 2016 CPT manual that describes the service performed. Clinical Policy and Programs DMA, G0478 (immunoassay with machine read result) - $18.03 GO477 ended January 2017

You Tube Narrated Slide Set On Office-Based Urine Drug Screening
Part 1 Part 2

Family Monitor

Symptoms of DCS Prescription Drug Monitoring Programs
Guam is 30 miles long Prescription Drug Monitoring Programs

Case continued: You decide that patient deserves a “trial” of a controlled substance. Your designated representative queries the CSDB and determines no new information has been added since your previous query. You continue the patient on gabapentin and meloxicam and begin tramadol 50mg QID and dispense 60 tablets and reschedule patient in two weeks. You present your treatment agreement which he quickly signs

Patient Case What is this patient’s risk of abuse, misuse, or other aberrant behavior? Low Medium High 1 2 3 4 5 6 7 ⃝

Set Realistic Goals Functional improvement
Not lack of pain. 50% pain relief in 50% of patients As best outcomes Will take substantial time One change at a time “Trial” of opioids What I hope to do Primary, atypical reactions to med How to think about pain patients How to start (or not) tx Non pharm, light pharm, medium pharm, opiates Function first, may be add stim, take something away

Treatment Agreements Only one physician/practice prescribes
Patient uses only one pharmacy Patient does not change dose without prior discussion with physician Clear policy on refills Patient agrees to consultations as needed Patient does not use illegal drugs Patient does not misuse legal drugs/alcohol Patient agrees to urine drug testing and/or pill counts Patient identifies a responsible person to confirm behavior related to medication use Elements of a typical therapeutic agreement include… Covenant vs contract God promises never again to destroy all life on Earth by flood[9:11] Covenant A covenant is a sacred agreement between God and a person or group of people. God sets specific conditions, and He promises to bless us as we obey those conditions. When we choose not to keep covenants, we cannot receive the blessings, and in some instances we suffer a penalty as a consequence of our disobedience. 89

Best Treatment Agreements
Office will call back within a specific time frame Patient will be seen in a timely fashion if pain flares Cost effective monitoring will be utilized If designated provider is not available, an associate will see patient and prescribe in accordance with the care plan Patient will be treated respectfully and confidentially If patient cannot comply with treatment agreement, opiates will be discontinued and other options will be offered Elements of better agreements include… Shared Power, sense of control 90

CDC Guidelines CDC recommendations for prescribing opioids for chronic pain outside of active cancer, palliative, and end-of-life care 1. Determining When to Initiate or Continue Opioids for Chronic Pain 2. Opioid Selection, Dosage, Duration, Follow-Up, and Discontinuation 3. Assessing Risk and Addressing Harms of Opioid Use

Second Level Tools Pain Issues Tramadol Butrans Nucynta
Serotonin syndrome This clearly depends on insurance coverage, but…… ma

TRAMADOL Weak Mu agonist, reuptake inhibitor 5HT/NE
Similar to levorphanol, is NMDA antagonist May be no different than acetaminophen Seizure and serotonin syndrome potential 75% bioavailability, 5-6 hr half life Metabolism 2D6, 3A4, 2B6, C19 2D6 metabolite O-desmethyltramadol is 200x more affinity for mu receptor and 9 hr half life

TAPENTADOL Mu agonist, weak (50 x less than MS but 30% of analgesic effect of MS) NE reuptake inhibitor 600mg max dose Half life of 4 hrs Metabolism by 2C9, 2C19 and 2D6.

TAPENTADOL Nucynta ER 50, 100, 150, 200, and 250 mg 12 hr medication

BUPRENORPHINE Partial agonist with very high affinity for Mu, is weak antagonist at Kappa, 25-50x more potent than morphine. High first pass metabolism, high lipophilic, thus SL and transdermal helpful. 95% protein bound Incomplete reversal by naloxone QT prolongation Bioavailable 30%SL, 70%IM, 15% transdermal. Metabolism CYP3A4 to norbup and glucouronidation Half life hrs

Buprenorphine Addiction treatment Pain treatment Suboxone Subutex
SL buprenorphine/naloxone tabs or films Subutex SL buprenorphine Pain treatment Butrans Transdermal patch, 7days, 10-20mcg/hr Belbuca Buccal patch, mcg bid

Butrans Transdermal patch MCG doses of 5, 7.5, 10, 15, 20
Starting dose: 5 mcg if <30mg MEQ 10mcg if MEQ <30 mg30-80 mg Recommended BUTRANS Starting Dose5 mcg/hour10 mcg/hour

Belbuca Buprenorphine buccal film
MCG doses of 75, 150, 300, 450, 600, 750, 900 For bid dosing

Buprenorphine Pharmacology Remember!!
Very high affinity for Mu Will kick other opioids off of the receptor Partial Agonist Will turn the receptor on only part way Half life hrs Incomplete reversal by naloxone 95% protein bound Incomplete reversal by naloxone QT prolongation Half life hrs

Case continued: He returns and even though initially it seemed to be working he finds his pain has returned to previous higher levels, still wants to “try what has worked, no more of this fancy stuff”. You one again have your designated representative queries the NC CSRS and it is consistent with your assumptions. You continue the patient on gabapentin and meloxicam and begin oxycodone 5 mg /acetaminophen 325 mg QID and dispense 60 tablets and reschedule patient in two weeks.

Pain Assessment Risk Assessment Psych, SUD, family hx UDS Review Controlled Substance Database Informed Consent/ Treatment Agreement Patient education “Trial” of opioids Functional goals Put in the EPIC assists or give web site to them

Step Treatment of Pain Controlled Narcotics

Third Level Tools

Opioids Short-Acting Opioids Hydrocodone/APAP Hydromorphone Morphine
Long-Acting Opioids Transdermal Fentanyl Morphine ER Oxycodone ER Oxymorphone ER Hydromorphone ER Methadone Levorphanol Buprenorphine Tapentadol ER Hydrocodone ER Short-Acting Opioids Hydrocodone/APAP Hydromorphone Morphine Oxycodone w or w/o APAP Oral transmucosal fentanyl Oxymorphone Tramadol Tapentadol Short-acting opioids have a fast onset of action for titration to analgesic effect, making them useful for breakthrough pain, but they require frequent dosing to achieve adequate control of chronic pain. A rapid onset of effect usually is unnecessary for the treatment of pain that is continuous; however, even in chronic pain states analgesic requirements may fluctuate. Transient severe pain on a baseline of chronic pain is called breakthrough pain, and may be caused by activity or procedures (incidental pain) or may be unpredictable. Short-acting opioids should be used in conjunction with extended-release opioids to control breakthrough pain. For persistent continuous pain, extended-release formulations or drugs with long half-lives are preferred over short-acting agents, as they facilitate patient adherence with treatment regimens, provide consistent levels of analgesia, and allow the patient to focus less on pain and pain medications. Patients and caregivers need to be warned that extended-release preparations become immediate-release if tablets are crushed or chewed, increasing the potential for overdose. Extended-release oral formulations are available for several opioids, including morphine and oxycodone. A continuous-release transdermal formulation of fentanyl is designed to provide effective pain control for up to 72 hours. An alternative to these pharmaceutically designed long-acting formulations is methadone, which may only require dosing every 8 hours due to its long half-life. However, this same property makes it somewhat challenging to titrate initially, especially in older patients with unpredictable and variable pharmacokinetics and increased opioid sensitivity. Lucas LK, Lipman AG. Recent advances in pharmacotherapy for cancer pain management. Cancer Pract ;10(suppl 1):S14-S20. EXALGO is ER hydromorphone. EXALGO™

Opioid Efficacy

Opioid Efficacy in Chronic Pain
Most literature surveys & uncontrolled case series RCTs tend to be short duration though some up to 24 months Sample sizes tend to be <300 pts Many pharmaceutical company sponsored Pain relief modest Some statistically significant, others trend towards benefit Cochrane review 2010 with 44% showing at least 50% pain relief Functional endpoints few thus improvement not demonstrated Not substantially different than the Cancer Pain literature Core point: Limited evidence of efficacy in setting of chronic pain but there is evidence of effectiveness in selected situations. RCT’s tend to be short though some up to 24 months and sample sizes tend to be small Many are pharm Pain relief modest but Balantyne JC, Mao J. NEJM 2003, Nobel M 2010 Martell BA et al. Ann Intern Med 2007; Eisenberg E et al. JAMA. 2005

Noble, et al Cochrane Review 2010
Long-term opioid management for chronic non-cancer pain, conclusion stated: 23% discontinued to do adverse events, including lack of effect Weak evidence suggests that there is clinically significant pain relief Improvement in QOL and functional status is inconclusive Serious adverse events, including iatrogenic opioid addiction, are rare. Long-term opioid management for chronic noncancer pain, (Review) CONCLUSION as per the report……”Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.”

Opioid Efficacy In the absence of adequate evidence it is wrong to conclude that: Opioid drugs lack long-term effectiveness Risks exceed benefits overall, or in subpopulations Alternative conclusions are equally likely: Some patients benefit, some are harmed Some subpopulations may be “over-treated” and some are “undertreated”. Although the data are mixed, the systematic reviews generally support the efficacy of opioid therapy for a period of months and suggest that a subpopulation can benefit long-term  But there is no high-quality evidence about long-term effectiveness Portenoy 2014 Portenoy 2014

Case continued: Risk Factors:
Family History – mother had depression, father & paternal uncle were “stoners” in past “Kind of mopey” Smoker / ? Alcohol Use Disorder Disability for a year / manual labor job Obesity 16 year old son is “running with wrong crowd” Age

Chronic Pain Partners Sleep disorders Substance Use Disorders
Depression/Anxiety PTSD Bipolar Disorders Personality Disorders

Pain Management

Pain Pharmacology

Pharmacologic Treatments
Alpha-2-delta ligands, SNRI’S, tricyclics, beta-blockers, antidepressants NE agents, etc. Tramadol, Avoid opioids in Migraine and Fibromyalgia NSAIDS oral Topical Duloxetine Tramadol Opioids last option Alpha-2-delta ligands SNRI’s Tricyclics Anticonvulsants NMDA antagonists Etc Tramadol Opioids last option Once you move into pharmacologic treatments it is helpful to once again consider the type of pan condition you are treating. On the Left of this slide you see nociceptive pain (LINK to nociceptive pain tx). As you know, classically the treatments are NSAIDS. Duloxetine has indications for nociceptive pain related to back and knee and is worth considering. (LIND to duloxatine indications). Tramadol has minimal opioid function, mostly working through serotonin norepinephrine. It has minimal addictive potential. Tapentadol has clear opioid function but also works through norepinephrine. It has less addictive potential clinically. Both of these are unique and tend to be less problematic than opioids relative to abuse. I commonly use them as a half step up the ladder towards regular opioids, avoiding some degree of risk. On the Right you can see some of the pharmacologic options for neuropathic pain (LINK to neuropathic pain tx). These range from agents such as gabapentin all the way to ketamine. Again you see tramadol and tapentadol as mid way options. On the Top you again see many of the same agents used for neuropathic pain. In many ways sensory hypersensitivity (AKA central sensitization) can be considered a special subset of neuropathic pain, thus the same meds are applicable. Noted here is the caveat that most protocols state that opioids should be avoided in headache or fibromyalgia due to the potential for progression of the disease or other unhelpful outcomes.

Neurobiology 101 Glutamate (N-Methyl, D-Aspartate) - ON
GABA (gamma amino butyric acid) - OFF N-methyl, D-aspartate receptor The activation of NMDA receptors has been associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors. Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization, leading to a heightened level of pain.[7,9,10] The reduced function of opioid receptors is caused by a decrease in the opioid receptor's sensitivity. This decreased sensitivity, in turn, translates to opioid tolerance as patients will require higher doses of opioids to achieve the same therapeutic effects.[9] Therefore, NMDA antagonists may have a role in these areas of pain management.[

NMDA Antagonists Methadone Tramadol Dextramethorphan
Tapentadol (theoretically) Ketamine Memantine Acamprosate Atomoxetine

Case Continued: Patient returns 1 month later:
Oxy 5/325 QID; Meloxicam 15 mg qd; Trazodone 50 mg qHS; Gabapentin 600mg TID He has been compliant with his medication, has been exercising nearly daily for 20 minutes per day, and is down to less than half-a-pack a day of cigarettes. His PHQ-9 is 3 (normal) He wonders whether he can “stretch the appointments out...the copays are killing me” His UDS is positive only for oxycodone What would you like to do? Let's return to the case presented earlier: One month later: The patient is currently taking oxycodone 5 mgs, every six hours, 120 per month, as you’ve prescribed. He rates his pain as “15” out of 10 all the time and describes no improvement in function. Should you increase his dose of oxycodone? Daniel Alford, MD, MPH 118

Case Continued: Oxy 5/325 QID; Meloxicam 15 mg qd; Gabapentin 600 mg TID; Trazodone 50 mg You check the CSDB and find that he filled a script for 12 Percocet 5/325 from his dentist 2 weeks ago. Now what would you like to do? Let's return to the case presented earlier: One month later: The patient is currently taking oxycodone 5 mgs, every six hours, 120 per month, as you’ve prescribed. He rates his pain as “15” out of 10 all the time and describes no improvement in function. Should you increase his dose of oxycodone? Daniel Alford, MD, MPH 119

Common Theme of All Guidelines!
Whenever there is aberrant behavior you should document an intervention!

Case Continued: He re-signs a patient agreement
You choose to continue the trial of opiates: oxycodone 5 mg /Acetaminophen 325 QID #120 along with the meloxicam 15mg, gabapentin 600mg TID, and the trazodone 50 mg qHS Additionally you give him another flyer on and ask him to contact them and to return with a quit date He is to keep an exercise diary Let's return to the case presented earlier: One month later: The patient is currently taking oxycodone 5 mgs, every six hours, 120 per month, as you’ve prescribed. He rates his pain as “15” out of 10 all the time and describes no improvement in function. Should you increase his dose of oxycodone? Duexis $1620/Mo 800/26.6 ie $18/each Ibuprofen $.30 each Pepcid famotidine $.20 = $.50 for the combo $45/Mo Silenor – 3mg/6mg $415/month = $14 each doxepin <$1 each Daniel Alford, MD, MPH 121

Case Continued: Patient returns 1 month later: He has quit drinking
He is sleeping through the night now on 50 mg Trazodone at HS. He contacted the Quit line and has set a quit date for his birthday next month. His PHQ-9 is 4 (normal) now that he is sleeping His wife is with him today and states he seems like “his old self before the hip surgery” His UDS is positive only for oxycodone The CSDB shows no other activity You pinch yourself and you’re not dreaming this Let's return to the case presented earlier: One month later: The patient is currently taking oxycodone 5 mgs, every six hours, 120 per month, as you’ve prescribed. He rates his pain as “15” out of 10 all the time and describes no improvement in function. Should you increase his dose of oxycodone? Daniel Alford, MD, MPH 122

OPIOID PHARMACOLOGY

Opioid Receptors Mu receptors analgesia, respiratory depression, euphoria, sedation, decreased gastrointestinal motility, and physical dependence. Kappa receptors spinal analgesia, sedation, dyspnea, dependence, dysphoria, and respiratory depression. Delta receptors effects are not as well studied, psychomimetic effect, miosis, respiratory depression, euphoria, dysphoria, dyspnea Strongest binding site for intrinsic opioid system

Classification Agonists Antagonists (Mu) Agonist/Antagonist
Oxycodone, oxymorphone, hydrocodone, morphine, methadone, codeine, fentanyl, tramadol, tapentadol Antagonists (Mu) Naloxone, naltrexone, nalmefene, diprenorphine Agonist/Antagonist Butorphanol, nalbuphine, pentazocine Partial Agonists Buprenorphine, meptazinol

Opioid Categories Naturally occurring Semi-synthetic Synthetic
Morphine, codeine, thebaine Semi-synthetic Oxycodone, oxymorphone, hydromorphone, buprenorphine, Synthetic Fentanyl, methadone, remifentanil, tramadol, tapentadol

Opioid Side Effects Common Uncommon Constipation Nausea Sedation
Confusion Sweats Dry Mouth Pruritus Hyperalgesia Myoclonus Delirium Urinary Retention Seizures Respiratory Depression Endocrine dysfunction Common Uncommon

Opioids – specific characteristics
IR vs LA Abuse deterrent LA with instant release with alcohol More commonly associated with hyperalgesia NMDA inhibitors Serotonergic

Once/Day or Every 12 hours
Dosing Frequency Immediate Release Product Every 4 - 6 hours Every 12 hours Once/Day or Every 12 hours Once/Day Every 3 Days Every 7 Days Codeine  Morphine Hydrocodone (Vicodin) Hydromorphone (Dilaudid) Oxycodone (Percocet) Oxymorphone (Opana) Tramadol (Ultram) Tapentadol (Nucynta) Targiniq – approved 7/14 oxycodone/naloxone extended release/long acting along with Embeda has the FDA Abuse-Deterrent Opioids labeling 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20 mg tablets Hysingla – approved 11/20/14 Purdue) 20, 30, 40, 60, 80, 100, 120 > 80 only for opioid tolerant Zohydro ER approved 10/13 Zogenix 10, 15, 20, 30, 40, 50 has submitted supplemental New Drug Application for abuse-deterrent preparation

Dosing Frequency Extended Release Product Every 8 or 12 hours Every 12 hours Once/Day or Every 12 hours Once/Day Every 3 Days Every 7 Days Methadone (Dolophine)  Morphine sulfate CR (MS Contin) Tapentadol (Nucynta ER) Oxymorphone HCl (Opana ER) Oxycodone HCl (OxyContin) Morphine sulfate ER (Kadian) Morphine sulfate ER-Naltrexone (Embeda) Morphine sulfate ER (Avinza) Hydromorphone HCl ER (Exalgo) Fentanyl Transdermal (Duragesic) Buprenorphine Transdermal (Butrans) Targiniq – oxycodone/naloxone extended release/long acting along with Embeda has the FDA Abuse-Deterrent Opioids labeling Accessed Jan 2014.

Dosing Frequency Extended Release Product Every 8 or 12 hours Every 12 hours Once/Day or Every 12 hours Once/Day Every 3 Days Every 7 Days Hydrocodone (Zohydro ER)  Hydrocodone (Hysingla ER) Oxycodone/Naloxone (Targiniq) Tapentadol ER (Nucynta ER) Fentanyl Patch (Duragesic) Buprenorphene Patch (Butrans) Targiniq – approved 7/14 oxycodone/naloxone extended release/long acting along with Embeda has the FDA Abuse-Deterrent Opioids labeling 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20 mg tablets Hysingla – approved 11/20/14 Purdue) 20, 30, 40, 60, 80, 100, 120 > 80 only for opioid tolerant Zohydro ER approved 10/13 Zogenix 10, 15, 20, 30, 40, 50 has submitted supplemental New Drug Application for abuse-deterrent preparation Accessed Jan 2014.

Specific Drug Interactions
Product Alcohol* PGP inhibitors CYP 3A4 inhibitors/ inducers CYP 450 inhibitors/ Benzodiazepines MAO inhibitors Class IA + III antiarrhythmics Morphine sulfate ER (Kadian)  Morphine sulfate CR (MS Contin) Morphine sulfate ER-Naltrexone (Embeda) Oxycodone HCl (OxyContin) Oxymorphone HCl (Opana ER) Hydromorphone HCl ER (Exalgo) Methadone (Dolophine) Tapentadol (Nucynta ER) Fentanyl Transdermal (Duragesic) Buprenorphine Transdermal (Butrans) P Glycoprotein Inhibitors:Amiodarone, Azithromycin. Captopril, Clarithromycin, Cyclosporine, Piperine, Quercetin, Quinidine, Quinine, Reserpine, Ritonavir, Tariquidar, Verapamil

Opioids – specific characteristics
IR vs LA Abuse deterrent LA with instant release with alcohol More commonly associated with hyperalgesia NMDA inhibitors Serotonergic

Hyperalgesia vs Allodynia
The word hyperalgesia means an increased response to a painful stimulus. The word allodynia means a painful response to a normally innocuous stimulus. Two of the most commonly used terms in the pain research and medicine world are hyperalgesia and allodynia.

Hyperalgesia vs Allodynia
Decrease dose/Eliminate narcotic Change narcotic Two of the most commonly used terms in the pain research and medicine world are hyperalgesia and allodynia.

Serotonin Syndrome (toxicity)
Irritability Tremor / Seizures Hypertension Tachycardia Hyperthermia Hyperreflexia Dilated pupils and diarrhea may not occur with due to opiate effect

Drugs Known to Cause SS SSRIs ; SNRIs TCAs Tramadol Dextromethorphan
Meperidine Methadone Fentanyl Buspirone ?Oxycodone Triptans are culprit Ochsner J Winter; 13(4): 533–540.

Opioid Stimulation Syndrome

Prescription Opioid Use N=12 Men and Women (24 total)
Route 100% pill 45% crush/snort 62% chew 29% inject Motive for use 91% energy (100% women 83% men) 83% pain (100% women and 66% men) 82% euphoria/pleasure 50% stress 47% withdrawal Published in final edited form as: Addict Behav August ; 36(8): 829–834. doi: /j.addbeh Characteristics and Correlates of Men and Women with Prescription Opioid Dependence Sudie E. Back, Ph.D., Katie Lawson, M.A., Lauren Singleton, B.S., and Kathleen T. Brady, M.D., Ph.D. Department of Psychiatry and Behavioral Sciences Medical University of South Carolina Abstract Back PhD 2011

Opioid Stimulation Syndrome
Sleep reduced consistently Irritability Thoughts racing Physical agitation Myoclonic jerking Night time movements Distractible Impulsivity So, in a little more detail, what do I is see clinically????? In a group of individuals taking opiates, in my practice I will say that about 25-40% of my case load, I see the following clinical elements, presented in order of their importance…… FIRST…..These individuals are sleeping very poorly. There is a consistent and substantial reduction in sleep. This is not the variable sleep pattern of pain patients where they may sleep 3 hrs tonight, 5 hrs tomorrow night, some napping scattered through the day at times due fatigue from lack of sleep, crashing for 8 hrs after a number of days of no sleep. This is a group that does not sleep more than 3-5 hrs night after night, week after week, month after month. They will at times relate this only to pain, but the persistence and level of sleep debt is substantial and consistent. (((sleep meds??))) SECOND…..they are irritable, very irritable. These are the patients you do not want to see on your schedule. You know who they are, you can think of some of them right now as you sit here. Your staff knows them well also, no one wants them. They feel like very difficult personality disorders. This is why my practice has a large number of them, no one wants to take care of them. THIRD…..they have racing thoughts. They do not tend to be talking faster than usual but they find their thoughts go much faster then the baseline they have known through their lives. Their minds are too full, not too empty, not dull and opiated as would be expected. They may not feel cognitively clear but it is not from sedation or slowness, they are over-stimulated cognitively. FOURTH….They are somatically agitated, feel uncomfortable in their bodies, over activated physically. At times they have myoclonic jerking day or night. They have odd wandering arm or hand gestures with sleeping that their partners comment on. FIFTH…they are distractible. They can’t focus well on a tasks, find they can’t complete things as they could in the past, wander at times from thing to thing, not staying on track. SIXTH…they are impulsive. They are not able to keep themselves from taking action on emotional states even when they may have been clear previously that they would not do particular behaviors again. The most commonly noted behavior in our clinics is that they tend to overuse their medication, repeatedly, even after sincerely promising that they would not overuse again. They are unable to contain their internal emotional intensity in a way that is consistent with even their own long term behavior goals. They don’t have “affective constancy” and will look like patients that are simply lying and manipulative.

Treatment Options Opioid rotation Opioid reduction Methadone
Away from the stimulating opiate Opioid reduction Methadone Opioid holiday WHY would I even bother teaching you about this? This is the patient that you don’t want to see on your schedule. This is the moody, irritable, crying, clinical catastrophe that all of your staff know, that you know, that takes a substantial part of your time. This may well be the person you want to refer but if you can identify them in the early stages you may be able to help.

Mechanism Glial cell activation Alternate opioid receptor
Microglia, astrocytes intracellular debris, heat shock proteins, other inflammatory stressors, and OPIOIDS. Illness response Alternate opioid receptor G-protein 7 inhibits cells G-protein 6 activates cells The effects of this activation is not just the positive feed back loop that is enhancing to further glial activation and pain, but also causes other global effects such as the “illness response”. The “illness response” is best thought of as the flu like sx set that we all suffer at times. It consists of increased sleep, fever, decreased intake of food and water and enhanced pain (sometimes generalized myofascial pain). This has been shown to all be created by glial cell activation and proinflammatory cytokine release within the brain or spinal cord. (Watkins 2009)

Naloxone Nasal Spray Standing Order in NC Request of any pharmacy
Given to anyone who has contact with someone using opioids of any kind.

Anesthesia Interventions
A potential source of spinal pain is the posterior zygapophysial joint (facet, Z joint), which adjoins adjacent vertebrae and is innervated by medial branches of the dorsal spinal nerves at 2 levels; however, there is no single history or physical examination finding considered pathognomonic for Z joint syndrome. For diagnostic medial branch nerve block, an evidence-based review found strong evidence in support of the use of diagnostic medial branch nerve block in the evaluation of chronic spinal pain, including documentation of diagnostic accuracy, reproducibility, and safety.( Anesthesia Interventions

Interventional Pain, Peripheral
Trigger Points Dry needling, lidocaine, steroids Peripheral blocks Geniculate US guided Articular and periarticular Regional Botox Migraine spasm

Interventional Pain, Axial
Epidurals Translaminar Transforaminal Facet injection Diagnostic Ablation Hot Cold

Interventional Pain, Stimulation
Spinal Cord Stimulation (SCS) Low frequency High frequency Dorsal root ganglion Peripheral stimulation Facial Peripheral Deep brain stimulation

Anesthesia Interventions
A potential source of spinal pain is the posterior zygapophysial joint (facet, Z joint), which adjoins adjacent vertebrae and is innervated by medial branches of the dorsal spinal nerves at 2 levels; however, there is no single history or physical examination finding considered pathognomonic for Z joint syndrome. For diagnostic medial branch nerve block, an evidence-based review found strong evidence in support of the use of diagnostic medial branch nerve block in the evaluation of chronic spinal pain, including documentation of diagnostic accuracy, reproducibility, and safety.( Anesthesia Interventions

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