Well, greetings, everyone. My name is Tony Decker, and I'll be talking about the challenges of pain and addiction. I am currently the Chief Medical Officer for the Division of Developmental Disabilities. I retired after 37 years with the federal system. I retired from the Gallup Indian Medical Center, and then previous to that, I was with the VA system in Prescott, Arizona, and prior to that, I was with the military at Fort Belvoir Community Hospital, which is also known as Fort Alexander Military Medical Center now. I graduated from osteopathic medical school at Michigan State University in 78. I completed a family medicine residency and an adolescent young adult medicine fellowship. I served as a public health service scholar on Chicago's South Side for 14 years, and I've had professorships in several universities. I do not have any conflicts of interest. I have no relationship with pharmaceuticals or prohibited donors. I am the past president of the American Osteopathic Academy of Addiction Medicine, which is the sponsor for this course. And although I've been employed by the U.S. Public Health Service, Job Corps, Indian Health Service, the Department of Defense, and the VA, and the state of Arizona, I do not represent any federal or state organization, and my opinions for this program are simply educational opinions of myself. Objectives for this course. Number one, I'd like you to be able to describe the relationship of pain and substance use disorders. Number two, you should be able, at the end of this course, to be able to screen for substance misuse, abuse, and diversion in patients with chronic pain medications, taking opioids. You should be able to implement non-pharmacologic and non-opioid pharmacologic interventions for pain, but we have some precautions to go over. And you should safely implement a tapering process, which is a challenging process to go through, and highly associated with rapid tapers or termination of opioids, highly associated with increasing events of suicide completions and increasing events of opioid overdoses. We'll talk about that in more detail. You should also be able to integrate the use of buprenorphine for the reductions of opioid misuse and also reduction of pain perception and improvement of function. So when we look at the incidence of chronic pain across the country, we realize a few things. Chronic pain actually affects more people than diabetes, coronary artery disease, stroke, and cancer combined. About 100 million Americans from the Institute of Medicine suffer from chronic pain syndromes that decrease your overall ability to function. When we look at people with low back pain, it's the most common complaint for pain in the U.S. 27% of people who complain of pain complain of back pain. Severe headaches and migraine pain is about 15% of pain complaints. Cervical pain, about 15%. And facial pain or facial aches, about 4%. When we look at the number of adults who report limited physical activity because of low back pain, 28% of people who have low back pain have to limit their activities compared to 10% of adults who do not have low back pain. Compared to people without low back pain, adults reporting low back pain were five times more likely, I'm sorry, three times more likely to be in fair or poor health by self-report and four times more likely to experience serious psychological distress. Now, the economic impact of people who experience chronic pain syndrome exceeds $600 billion annually. And as we said before, about 116 million Americans, it's about $2,000 per person per year. Chronic pain is the most common cause of long-term disability with low back pain. And it affects about 90 million lost work days per year. Over 7 million people are partially or severely disabled because of chronic pain syndrome. I apologize, I am also, not only am I a presenter, but also I have a chronic back problem. And so I just had to adjust my bullseye. When we look at the emotional impact of chronic pain, it definitely has an impact on mood, on memory, relationships, and the overall quality of life. Chronic pain often causes frustration, anxiety, and depression. And we'll talk more in the next slide about that. Negative emotions can make the perception of pain worse and worsen anxiety and depression and other emotional problems. Current VA study looked at the relationship between veteran suicides and pain and the reduction of opioid medication. This is the OLIVA study, which is available to you in the program. And they were able to see with looking at millions of veterans in the VA healthcare system, when opioids were decreased and or terminated, there was a dramatic rise in both suicides and in opioid overdoses with inappropriately obtained opioids. We look at pain and depression. About half of all people who have severe chronic pain have depression. Chronic pain can diminish job performance, can lower motivation, especially to physical activity. It can also decrease performance of your activities of daily living and family obligations. So household chores, childcare, financial contribution, and reduction of full participation in usual family activities can be lost. Or in other words, you would have more loss of participation because of chronic pain. Intimacy issues, including sexual contact and intercourse, can also be significantly affected because of chronic pain. When we look at chronic pain and fatigue, chronic pain can affect sleep. It can modulate stress hormone levels. It can decrease the ability to cope with stress. And the maintenance of a healthy lifestyle can be impaired by chronic pain. Poor diet, lifestyle habits, sleep hygiene, insufficient exercise can be predictors of poor coping skills when people have chronic pain syndromes. When we look at chronic pain, we start to realize several things. Most primary care providers and many specialists find the management of chronic pain very challenging. Several studies have looked at primary care physicians who have decided to stop prescribing Schedule 2 opioids in their practice simply because of a desire to avoid this patient population and the consequences of prescribing opioids having significant problems. In Arizona, the number one reason for a doctor to be referred to the Board of Medical Examiners is something happened to a member or a patient and you prescribe them opioids. That's the number one reason to be referred to the Board of Medical Examiners. The number two reason to be referred to the Board of Medical Examiners is a provider who either rapidly decreases opioid prescribing or terminates opioid prescribing. So in many ways, you're damned if you do and damned if you don't. Opioid use is associated with significant risks, especially at higher doses, greater than 90 morphine milligram equivalents. And that includes opioid use disorders, hyperalgesia syndrome, and mortality and morbidity with dose-dependent effects. We look at the chronic pain treatment model. We have several options. Obviously, we're speaking of medications, but the medications can be both opioid and non-opioid. They can be oral, topical, intravenous, intramuscular, or intrathecal. Modalities for non-pharmacologic interventions include physical therapy, occupational therapy, range of motion, body work, acupuncture, anti-cutaneous nerve stimulation, osteopathic manipulative therapies. Exercise and weight loss are probably two of the most successful interventions for chronic pain syndrome related to low back or spine pain. Rehabilitation services, dietician care, nutrition, all are used in this particular area. Interventional services such as superficial, topical, analgesic agents and anti-inflammatory agents, joint injections, selective nerve root injections, sympathetic chain injections and or stimulation, epidural spinal injections, radiofrequency ablations, cryotherapy, spinal cord stimulators, and intrathecal pumps are all possible. Obviously, surgical intervention too, which is commonly used to treat back pain but has a very poor beneficial effect when you look at the long-term people who have spinal surgical services with some exceptions. They have some benefit in certain situations such as caudicoenter syndrome and things like that. From a behavioral health standpoint, psychiatry, cognitive behavioral therapies, biofeedback, mindfulness support groups have been used for patients in chronic pain syndrome. And I should add that all of these items are typically used in a chronic pain multidisciplinary intervention package. Complementary or alternative care services, body work, yoga have been used with significant amounts of success. From a medication standpoint, we'll go into more detail about this. Typically, we have the non-steroidal anti-inflammatory agents, acetaminophen, brand name Tylenol, anticonvulsant medications, which include the gabapentanoids, the SNRIs and the SSRIs, and the MAO inhibitors, tricyclic antidepressants have been used in lower doses with some success and helping with the sleep cycle issues such as amitriptyline for 10 milligrams, things like that. NMDA antagonists, corticosteroids, viscous supplements, especially in the joint areas, anesthetic patches, muscle relaxants. Some people are using homeopathic agents, which are infinitesimally small doses of medications. Biologics have been used with significant benefit for autoimmune disorders, medication-assisted therapies, including buprenorphine and methadone to help patients who have chronic pain syndrome and are substituting opioids with the MAT medications. And obviously, opioids are a choice and have been used for thousands of years for pain syndromes. Future medications may be the non-classical opioid receptor agonists. There's been a significant amount of work with CB1 and CB2 agonism. THC has some benefits for some patients, but there's been very questionable research with the high-potency THC. And then the whole area of medical marijuana, keeping in mind that marijuana has changed dramatically from the 1970s to the 2020s with quadruple THC potency in many of the hybrid marijuana products. When we look at non-opioid treatments, we have the cognitive behavioral therapy, intervention strategies, more from a patient education, engagement process, exercise therapy, and weight management have significant benefits. Some of the weight loss and creatine-type medications are being used in non-diabetics with significant need to change their body habitus have had an impact in regard to chronic pain syndrome and especially low back pain. First and second line options include acetaminophen and non-steroidal anti-inflammatory agents. One of the things to remember with acetaminophen is that it has a three gram max per day. Now in the European Union and the Commonwealth, the UK and UK-related countries, you can't buy a bottle of 500 acetaminophen tablets. You can get smaller bottles and their overdose rates of acetaminophen are a fraction of the overdose rates seen in the US. So acetaminophen has been associated with about 50,000 liver failure cases per year. Non-steroidal anti-inflammatory agents are associated with between 16,000 and 20,000 perforations per year with 9,000 deaths. The gabapentinoids associated with high levels of falls and fractures secondary to loss of stability, almost all of these being ground-level falls. The SNRIs and the SSRIs and the TTAs have had some benefit. Benlafaxine has been used even though it doesn't have an indication, but it has a very similar effect in regard to the SNRIs benefiting the perception not only of chronic pain but also the resultant depression. Tricyclics are used in much smaller doses, so just 10 milligrams rather than 50 and 100 milligrams. TCAs sort of fell off the market in regard to antidepressants because of the high likelihood of cardiac arrhythmias with intentional overdoses and so never give somebody enough to hurt themselves. So 10 milligram tablets in smaller volume becomes the choice. Topical modalities and interventional treatments, as we described before, multimodal, multidisciplinary approaches are typically more favorable than a single modality. So when we look at the non-opioid risks, acetaminophen, as I said before, has a toxicity threshold that ranges from two to four grams, and the FDA max currently is three grams, and even that is for healthy livers. People with end-stage liver disease or any other type of liver disorder, regardless of the etiology, should be on lower-dose acetaminophen if not no acetaminophen. As I said, you know, we're talking about a large number of liver damage that occurs in the U.S. because of acetaminophen use. Non-steroidal anti-inflammatory agents, both COX-1 and COX-2, so your COX-1 or your over-the-counter ones, be wary of long-use cardiac arrhythmias, GI perforations, chronic kidney disease, especially in the presence of dehydration, and problems with anticoagulants causing a platelet aggregation disorder with long-term use. And aspirin itself can cause problems. Even though there's a beneficial effect of aspirin from a joint standpoint as an anti-inflammatory, it does have significant platelet aggregation changes. As I said, the gabapentinoids, gabapentin and pregabalin, are associated with falls, dizziness. It appears to be dose-related, and it appears that if it occurs in the gabapentin population, it most likely will occur in the pregabalin population too. Careful titration from low to higher doses, and a clear description of complications and an informed consent, especially if you're using it with opioids. SNRIs, loading and tapering strategies. It's rare to have a person have serotonin syndrome, but you need to know, and the patient needs to be aware of, the symptoms that go along with that. Tricyclics, as we talked about, have cardiac and dizziness-associated risks. One of the nice things about tricyclics is even in low doses, 10 milligrams of amitriptyline can cause significant sedation. And so if a patient takes that just before they go to bed, and they have good mattress support for their lumbar and their cervical spine, they should be able to fall asleep and have some rest for those muscles that are in spasm. Corticosteroids, patients that have inflammatory disease, have a significant positive reaction, but hormonal changes and glucose metabolism changes and osteoporotic changes are all complications from chronic use. So that needs to be taken into consideration. We look at the lidocaine analogs, especially the topical lidocaine gels and even injected lidocaine, if it's a significant amount. Cardiac arrhythmias and other toxic effects of lidocaine can occur. Clearly, patients on lidocaine patches should not be using more than one patch per day, and they should remove the previous patch when they put a new patch on. There's still a significant reservoir of lidocaine in the patch when it has been on for more than 24 hours. Muscle relaxants, in a large variety of them, have a high association with fatigue, sleep changes, and fall risks. Goals of treatment for patients with chronic pain would be, number one, to improve quality of life, function, and performance of the activities of daily living. Now, we all remember in the late 1990s, early 2000s, when the Joint Commission and the Institute for Healthcare Improvement decided that pain is a vital sign and that we need to assess for pain on every visit. Subsequently, there was a 400% increase in opioids prescribed in the U.S. and there were several pharmaceuticals that tried to tell us that opioids are safe. And clearly, the epidemic of opioid overdose events started to be more frequent. We want to ensure safe and reasonable treatment for underlying conditions. And this is a critical part of our job as clinicians to make sure that the cause of the pain can be identified. It doesn't relieve the pain, but if there's a cause for the pain that is identified, there may be interventions that would be beneficial for that particular cause of pain. Maintain a clear rationale for utilization based on the patient's risk factors and their response, and that's for all interventions. Encourage autonomy. In other words, a patient is a partner in this and we want them to have the autonomy of helping make that decision and what's best. That doesn't mean that they can demand medication from you, but they can definitely work with you in regard to the therapeutic dance that we have with our members. Coping and healthy lifestyle choices to improve the long-term outcomes, and that goes along with exercise, weight loss, range of motion, things like that. So when we look at our objectives in regard to trying to address chronic pain syndrome, will the patient be able to reasonably perform routine work and family obligations? If so, without opioids, how can we address their current complaints without opioids? If the intervention strategies are inadequate to address those routine work and family obligations, then we can think about non-opioid pharmacologic agents and other types of interventions. So you can see that opioids are never the first choice and they're never the only choice in regard to a patient who has chronic pain syndrome. Will the patient transfer, walk, routinely exercise, or will they remain sedentary? I always try to get corroborative information in regard to response to any type of pain intervention. And if the collaborating family member says, well, he's got no pain, but he just watches TV all day long, that is not a move in the right direction. So we want to make sure that we emphasize the function side of the equation more than just the pain relief side. Will the patient be able to perform activities of daily living and executive functioning without significant harm to themselves? And will the patient commit to behavioral modification and interventions when appropriate, which includes exercise, weight loss, range of motion, self-care, participation in support groups, things like that. Documentation becomes a critical part of how others evaluate your care. So we need to be able to assess the patients. We get a history, physical examination, and then we document signs and symptoms consistent with pain and dysfunction. Describe the setting and the provocative activities that lead to these complaints. Be descriptive, especially when you're starting to look at what type of pain this is. Is it myofascial pain, joint pain, facet, radicular, spastic, neuritic pain? And does it correlate with the examination findings? Does there a range of motion that is impaired? Is a strength evaluation consistent with the report from the member? And do you have any other special testing, positioning, range of motion, activities to help you determine if the patient's complaints are consistent with the findings? One of the things that you do not want to do is just routinely refill medications. And if you have a system where every 30 days the patient gets 180 MS-30s, that's going to create a significant problem for you in the future, and it's going to create a significant problem for the patient in the future. So when we start looking at this, we want to tailor the intervention strategies, both the non-pharmacologic interventions, the non-opioid pharmacologic interventions, and the opioid pharmacologic interventions to what the complaint is and how we can improve function. When we look at pain and nociception, the sensory nervous system response to certain harmful or potentially harmful stimuli becomes one of the things that we measure when the patient comes in and for the reassessments. So nociceptors, pain receptors, have a certain threshold that require a minimum intensity of stimulation before they trigger a signal to the axons, which travel to the spinal cord and to the brain for further modulation. One of the things that we have to realize is that this theory of nociceptors and brain modulation and pain perception has gone through an evolution from the sensory system to the gait system to the neuroreceptive pathway. So we have our nerve endings way out here on the left side of the slide, and local anesthetics, non-steroidal anti-inflammatory agents, and even opioids to some degree because there are mu receptors in the periphery have a beneficial effect. On the primary afferent nerve, local anesthetics can be very helpful. So radicular blocks and spinal nerve injections and facet rhizotomies may have a beneficial effect. When we look at the dorsal root ganglion, local anesthetics, alpha-2 agonists can benefit. The dorsal horn, we have ascending spinothalamic fibers and descending noradrenergic and serotonergic inhibitory fibers. So on the descending side, opioids have a benefit. The alpha-2 agonist, the tricyclics, and the SSRIs and the SNRIs. And then in the dorsal horn, we have opioids, gabapentinoids, and ketamine, which has become a substance that we're using more even though it is a substance of abuse, but there's many pain interventionists are using ketamine services. Now, opioid prescribing is a challenge. It became the most commonly prescribed substance. So hydrocodone in 2000 was the most frequently prescribed medication. And this is when we include antibiotics and diabetic medications and antihypertensives. In 2012, 259 million prescriptions are written for opioids, of which most were for hydrocodone, Vicodin, enough for one bottle for every adult American. In Arizona, we call it the Controlled Substance Pharmacy Monitoring Program. In most states, it's the Pharmacy Drug Monitoring Program. There was a 35% drop of opioid prescribing by 2018. Remember, around 2012 is when we were peaking the number of people who were overdosing on prescribed opioids. And so several programs had intervention strategies to decrease prescribed opioids. Many providers just decided we're gonna stop completely. We're not gonna give out opioids. And some people even had a sign on the door. We do not prescribe Schedule II pain medications. Now, in 2018, our governor declared mission accomplished because we were able to decrease opioid prescribing. In 2019, we had a 50% drop of all prescribed opioids compared to 2011. But we had a tripling of our overdose deaths. Now, at that time, fentanyl, illicit fentanyl, was rampant in Arizona. And just last, I should say, in March of 2024, the DEA has identified that Arizona is the state location of 56% of all the fentanyl that is interdicted in the US. In other words, of all the fentanyl that is identified by the authorities and confiscated, 56% of it is from Arizona or interdicted in Arizona. Now, currently, in all pharmacy drug monitoring programs, anyone who prescribes a Schedule II through V medication is monitored. The DEA has full visibility of that system. The pharmacy drug monitoring programs were initially set up to identify patients who were using too many providers or too many pharmacies in their efforts to get opioids. Currently, they continue to monitor that patient population, but they also monitor the prescribers. I don't think the DEA is hiding behind bushes waiting to pounce on you, but clearly, this is an open book for the DEA to look at your prescribing habits. They also measure the number of people on opioids and on benzodiazepines. They also measure, in several states, the number of people on opioids and the gabapentinoids, keeping in mind that pregabalin is a Schedule V, so that's automatically gonna be monitored, but some states are monitoring gabapentin prescriptions. Now, there are certain places where there is no monitoring. So the opioid treatment centers, in other words, the methadone clinics, that is not included in 2024 to the pharmacy drug monitoring programs. In addition to that, any medication given in a clinic, an urgent care center, or an emergency room. So when a patient comes in, in my time in the ER, would come in with a trimolecular fracture with severe pain response, I may give them 50 mites of fentanyl IV, stabilize the fracture, and then make sure someone else drives a member home. Now, in that scenario, that 50 mites of fentanyl will not be identified as a prescribed opioid. It is a dispensed opioid, and it's not part of the pharmacy drug monitoring program. There have been some proposals to include opioids that are dispensed by opioid treatment programs and in the emergency room, in the urgent care, or even in your office, if you're dispensing these medications. But at this point in time, they haven't established that. New regulations were established in 2018 in the state of Arizona. As I said, the DEA has full visibility of the pharmacy monitoring programs, and all states are now interactive, effective 2019, when Missouri became the last state to engage in the pharmacy drug monitoring program, on a statewide basis. St. Louis has had the program for several years. So 10 steps in the universal precautions in pain. Number one, have a diagnosis for the cause of pain. Reassess that diagnosis on a regular basis. Psychological assessment, including addiction risk and suicide risk should be provided. Informed consent to use any type of intervention should be standard of care. That includes both non-opioids, because we know that some of the non-opioids can have significant deleterious effects, especially patients who are renal or hepatic insufficiencies. But for patients on opioids, they need to have a informed consent to understand the risks, the benefits, and the alternatives to that intervention strategy. A treatment agreement. Notice I didn't say a treatment contract. Contract is a binding agreement between at least two different, if not more, individuals. You don't want a situation where you have obligated yourself to dispense or to prescribe opioids if a patient has a negative drug screen or something like that. A treatment agreement is an agreement between two, and there is no legal obligation to give the patient something despite their adherence or what appears to be an adherence to their intervention package. Assess the pain and function in both the pre- and post-intervention status. One good way to assess function is their activities. And establish, you know, tell me why you're coming in. I've got back pain. Tell me what things you cannot do. I can't put on my pants. My wife has to help me. I can't wipe myself when I defecate, and I have to have assistance to do that. Well, those are severe losses of activities of daily living. So what happens is that becomes an area that we're gonna measure for function as time goes on. Remember that when you give opioids, it is a trial. It is not a guarantee the person's gonna get this every time they come in, or if they have other issues that they want to have opioids. It is adjunctive to other medications and other treatments. There's a continued reassessment of the pain and the function of people who are in chronic pain care. And you're going to assess how well is the intervention working on analgesia? Has their activity increased? Are there any adverse effects? Falling, excuse me, falling asleep. And we'll talk a little bit about that in more detail. Aberrant behaviors, early refills, lost medication. Urine toxicology refusals, or urine toxicology with abnormal findings. And so we'll talk a little bit about that in a few slides. Periodic review of diagnosis, including substance use disorder or opioid use disorder needs to be monitored and careful documentation. Do not clone your charts. In other words, don't copy and paste every visit so you have the same verbiage, the same indentations, the same references on every visit. You need to make sure, and you can have a template, but you need to make sure there's evidence that you examined the patient, you made a diagnosis, you provided treatment, and you have a follow-up plan. Contact the Pharmacy Drug Monitoring Program. You can print a PDF off of that, have it scanned into the electronic record, and also regular urine drug screening. Now, in 2011, there was a peak for the opioid prescriptions in the U.S., and we also had a peak of prescription opioid deaths in the U.S., and then it started to decrease. There was a recognition that something is not right as we saw the increase of opioid prescribing and the increase in opioid deaths. The deaths were typically between the ages of 40 and 60 during the late 2000s and the 2000s. In 2023, the deaths are between 15 and 30, so we have dropped the age, and the reason is because fentanyl has become the leading cause of overdose deaths in the U.S. When we look at the long-term adverse effects, there's no doubt that there is a relationship between tolerance, you need more and more to have the same effect, dependence, if you stop taking the opioid, you go into withdrawal, and the possibility of an opioid use disorder or addiction. So there are risks that are there. That doesn't mean that you have to completely erase opioid prescribing from your practice. You need to be able to do it in a way that makes appropriate and legal sense. Opioid-induced endocrinopathies are common. This is a suppression of the hypothalamic-pituitary-gonadal axis. It typically is because of a drop in growth hormone-releasing factor. The most notable changes are sex hormones and vitamin D25-hydroxy. So these will change, and patients will have a change in their overall function. Amenorrhea or changes in menstrual cycles are common. Decreases in testosterone can cause a loss of morning erections, a decreased desire for sexual contact, and also frustration because of inability to maintain an erection during intercourse and things like that. So these changes shouldn't have a knee-jerk response to just prescribe testosterone or prescribe estrogens. It should be discussed with the patient in advance. They had informed consent. They gave that informed consent, and they understand that these are possibilities, and if this happens, let's talk about it, and we'll talk about intervention strategies. Hyperalgesia syndrome. It's increased pain because of long-term opioid use, and it's different from the original injury. So sometimes it's very difficult to diagnose because they may come in with L4-5 nerve root compression pain, but now they have achiness, like a toothache, all the time in their upper back. And so pain may gradually normalize if you actually decrease the opioid load. This is more pronounced in what's called a wind-up phenomena with fibromyalgia and atypical pain syndromes. This has also been seen in post-COVID-19, myositis and myalgia syndrome, respiratory syndrome, respiratory suppression and respiratory syndromes because of chronic obstructive lung disease, obstructive sleep apnea, reversible airway disease, and other apneic disorders may be complicated because of chronic opioid use. And then we've already talked about chronic pain is a cofactor in depression, anxiety, and sleep disorders. Opioids also can do that. However it does, the opioids do use the immune receptor system and the endorphins also use that system. So you have a competition against the endorphins with chronic opioid intervention. Societal impact, 10 million U.S. adults reported misusing prescription opioids in the 2000 teens. Prescription opioid misuse can progress to intravenous use, heroin use, fentanyl use, and other illicit drug use. All the people that used to inject in my practice now only inject either cocaine or methamphetamine. The opioids typically are smoked right now. The fentanyl tablets in Phoenix in 2024 are only 50 cents. And many of these tablets have over a milligram of fentanyl in them. It's a tragic situation going on right now. Drug poisoning deaths involving opioid analgesics were the rule happening in the late 2000s and the early 2000 teens. The use of prescription opioids with heroin or illicit opioids was common and quadrupled in regard to deaths from 1999 to 2014. There were 89,000 opioid-related deaths in 2022, 90% of them being secondary to fentanyl. The rates for 2023 are not back yet, but it looks like that number may be close to 100,000 overdose deaths. Rates for nonmedical prescription opioid use were greatest among Caucasian and Native American men in the Midwest and the West, annual incomes of less than $70,000 a year, previously married and with a high school level of education or less. Now, this is changing. This was the population in the early teens. What's happening now when we start looking at overdose deaths, it's young people. And unfortunately, that picture is getting younger and younger as time goes on. Prescription opioid use disorder is linked with a variety of mental health disorders. In the military, PTSD and opioid use disorder was common. The triad for the Gulf War and the Afghanistan Wars were PTSD, traumatic brain injury, chronic pain syndrome, and then resultant depression. Borderline personality disorder, schizotypical, and antisocial personality disorders are related to opioid use disorder and alcohol use disorders. Major depressive disorders and bipolar I disorders are also overrepresented in the prescription and the opioid use population versus the non-opioid use populations. When we look at safety, safe and effective opioid therapy for chronic pain requires not only clinical skills, but also knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid use, addiction, and diversion. Veterans have a higher risk ratio, both male and female, in this area because the number one reason an active duty service member seeks medical services is still pain, which is more common than in the general population. So the basics of pain, we have a four-step model. Transmission is an acute stimulation in the form of a noxious, either thermal, mechanical, or chemical stimuli, and it's detected by the pain neurons, the nociceptive neurons. Transmission is the nerve impulses that are transferred up the axon of the afferent neurons to the periphery, to the spinal cord, or from the periphery to the spinal cord, to the medial and ventral basal thalamus. And then it goes to the cortex, and it's processed as pain. Perception, the cortical and limbic structures in the brain are involved in an awareness and an interpretation of pain and modulation. So pain can be inhibited. We've all seen patients who have metastatic bone disease, and they are able to minimize the pain experience with really psychic intervention. However, most patients continue to have pain and have difficult times in modulating it. It's facilitated by mechanisms affecting the ascending as well as the descending pathways. Our goal here is not to take away people's ability to modulate pain, but to facilitate that process with pain-relieving interventions. So considerations to ask, is it medically reasonable to initiate or continue a current regimen? In other words, patient comes to you from another provider who's retiring. You have to reassess that patient from scratch. And you have to decide, is this something that I can do and benefit this member? If so, for how long and at what current dosage? Can we improve the safety? The patient has a prior history of falls, of motor vehicle events, of injuries that have been caused or could be related to their opioid use or their use of other intervention strategies. Is there evidence of aberrant drug-related behaviors? This is something that should be assessed, not in an accusatory fashion, but in a way that's collegial with the patient and respectful of the patient. And are supportive and evidence-based treatments being continually trialed? So sometimes patients move to your area, and you have to reestablish intervention strategies with a team in your area. Other times, patients already have a therapist or already have a physician or a physical therapist, chiropractor, naturopath, people that are working with the member that the patient feels that their function is improving. So what are the CDC opioid prescribing guidelines? Well, first off, the first set of guidelines came out in 2016. And so this is what they said, said, opioids are not the first line for chronic pain. If opioids are used, they should be combined with non-pharmacologic therapy, non-opioid pharmacologic therapy, establish and measure goals for pain and function with each assessment, and track accountability and progress. Prescribe the lowest effective level. Now, effective intervention may not be the same from person to person. So finding that sweet spot into what works for a patient may be a challenging process. Practice caution, especially when you're exceeding 50 mmes per day, and document the justification, including if you go above 90 mmes per day. Prescribe no more than is needed for acute pain. A patient comes in with a Colley's fracture. They have pain, but they got a splint put on yesterday in the emergency room. They still have a significant pain. They've got good neurovascular function in their distal digits. They may need to have three or four days. That's all. Keep in mind, if a patient has other things that complicate opioid prescribing, recurrent constipation, falls, dizziness, things like that, you need to be aware of all those risks. Use the opioid risk tools and document pain agreements, as we said before. And then rapid reductions or opioid termination is highly associated with overdose events and or suicides. Now, that was 2016. 2019, the CDC came out with another set of guidelines that were the same, but they said, please do not apply this to the general population. Individualize your assessment and your care for each person who presents. And it was a stepwise fashion, just like we do for hypertension. It was a stepwise fashion to provide intervention for chronic pain syndromes. So the 2016 side said, be careful. Use the PDMP. Avoid combination with benzodiazepines. Use multidisciplinary teams. Prefer for medication-assisted therapy with buprenorphine or methadone. And combine with behavioral therapies for high-risk members. And practice extreme caution when you're switching over to methadone. The key here is that methadone, and this is an issue because methadone has a wide variation in half-life from person to person, and a wide variation in half-life in the same person from time to time. So a half-life could be as short as four hours, but could be as long as 96 hours. So methadone is a drug that has wide variation and a multitude of drug interactions. So what was the purpose of those guidelines in 2016, 2019, then later on in 2022 and 23, the VA and the Department of Defense came up with guidelines too. So first off, it's to provide recommendations in opioid prescribing for chronic pain. And by definition, that would be pain lasting greater than three months. Outside of active cancer treatment, palliative care, or end-of-life care, the primary care clinicians should be looking at safety and documentation that is standardized. So 2019 said, do not apply generically, individualize the care. In 2022, the guidelines from the federal system, which included the CDC, was that buprenorphine could be used as a primary drug for pain and cautions rapid taper of opioids. Behavioral health assessments also necessary, especially in the area of depression and other psychiatric issues that could deteriorate to suicidal ideation. Signs of helplessness and hopelessness are critical to identify in a chronic pain patient. The medical legal aspects of chronic pain treatment with opioids, keep in mind that Schedule 1 is an illegal intervention. Now the feds have decided to call marijuana and have called marijuana a Schedule 1. Most states now have medical marijuana and many states have recreation use marijuana. So what happens is the federal government in our current administration has decided not to pursue personal use of marijuana products, including THC and all the other delivery systems, vaping systems, edibles, and things like that. Schedule 2 is limited to a 90-day max, but most states have a 30-day max for Schedule 2s. Then you have 3, 4s, and 5s, which can be called in, even though a Schedule 2 must be electronically sent in. When we had the recent event with Change Pharmacology, the UnitedHealthcare hacking, we went back to paper scripts, but that was a big change for many pharmacies because they have EHR as the primary method for sending in opioid prescriptions. PDMP monitoring, medical board complaints we've talked about, the DEA has dropped the waiver, which is the ex-DEA, and so that was dropped in 2022. Many states have a BNDD and a controlled substance registration that must be also given in certain states, so you have to have a DEA and a state license for prescribing opioids. Risk evaluation and mitigation strategies, the REMS, is pushed. The DEA requires eight hours of education in this area. This course qualifies for that, by the way, but most people have already achieved that intervention education requirement. So when we looked at the 16, 19, and 22 guidelines from the CDC, things have changed over the course of time. So why are these current guidelines so relevant? Well, it's the standard of care is number one. They want to improve the communication of the benefits and risks of opioids for chronic pain to patients and to clinicians, to improve the safety and effectiveness of pain treatment, to reduce the morbidity and mortality of long-term opioid therapy, and this is a significant concern. We want to help recognize appropriate referrals and initiation for medication-assisted treatment. Any prescriber with a Schedule III prescription can prescribe buprenorphine sublingual or intradermal for medication-assisted treatment or opioid dependence intervention. Stabilization should decrease the forced termination of opioids to stabilize members with minimal side effects. We look at our list of opioid options. Hydrocodone, codeine, hydromorphone, morphine, oxycodone, oxymorphone, and dependadol are all short actings. The long actings are interesting because you have methadone, which is intrinsically long acting, but there's also delivery systems that make short actings into a long-acting delivery system, such as transderm fentanyl. Keep in mind, when a person has a 50-mic per hour patch and they leave it on for 72 hours, 50% of the fentanyl in that patch is still there. There have been multiple literature-cited cases of pediatric overdoses to fentanyl because the grandson saw grandpa wear a patch, he finds it in the wastebasket, he puts a patch on, and two hours later, he's found in an uptended position. Animals also will eat the patch, and obviously, chewing the patch will result in a release of fentanyl, and overdoses occur in that population. So we have extended-release morphine, extended-release oxycodone, extended-release dependadol, and extended-release oxymorphone. When we look at morphine, that's the MSIR, MS-Contin, oral morph, sustained release, the onset of action is 15 to 60 minutes. The peak effect is 30 to 60 minutes. The duration of action is four to six hours. It's for moderate to severe pain. Morphine 6-glucuronide is an active metabolite. It's renally excreted, and then morphine 3-glucuronide has an excitatory effect, and that's one of the reasons why some people have agitation with the use of morphine products. I want to say that, and this could show up on the boards, 6-monoacetylmorphine is a metabolite of diacetylmorphine. Diacetylmorphine was developed by Bayer in the late 1800s. It is called heroin, but diacetylmorphine is, they add two acetyl groups to the morphine molecule. It crosses the blood-brain barrier faster, but the first thing the brain does is it clips off one of the acetyl groups. The only way you can have monoacetylmorphine is if you had diacetylmorphine in your system ahead of time. So it's pathognomonic for the presence of heroin. So any detection of monoacetylmorphine would be consistent with the use of heroin, keeping in mind that most of the heroin that comes into the U.S. now is actually fentanyl or fentanyl-augmented heroin. Codeine, typically found in Tylenol 2, 3s, or 4s, same onset of action, peak effect, same duration of activity, a little bit shorter duration in regard to the front end of activity. It's for mild to moderate pain. It has hepatic and renal elimination. 10% of the codeine is transformed to morphine. And that means that if you do a drug screen on someone who is taking Tylenol 4s and they pop up positive for codeine and morphine, that is what you would expect. Keep in mind that the opioid that is in poppy seeds is morphine. Now we used to have, and many people still screen for 300 nanograms per deciliter, when the screening test on the Department of Transportation is 2,000 nanograms. And that's because of the poppy seed problem. It is morphine, but it's a much lower level. And so you need to make sure that you understand that poppy seeds can cause a drug screen that's at a low level of sensitivity, in other words, a more sensitive drug screen to become positive. Again, that codeine does cross the placenta and is in the breast milk. Oxycodone, onset of action is 10 to 15 minutes, peak effect in 30 to 60 minutes, duration of action 3 to 6 hours, comes with a variety of preparations, moderate to severe pain, has hepatic and renal elimination. Should be noted that some poppy seeds, although they are highly regulated from New Zealand and Australia, have been genetically modified to have a plant-based oxycodone. So that should not be in the stores as part of dietary poppy seeds, but they have been able to change the technology in this area. These also cross the placenta and the breast milk. Hydrocodone, as we stated before, the number one drug prescribed in the late 2000 noughts and the early 2000 teens. Same thing, onset of action is 15 to 30 minutes, peak effect 30 to 60, and duration of action 48 hours. It's for mild to moderate pain, hepatic and renal excretion, and placenta and breast milk crossing. Hydromorphone is a metabolite of hydrocodone. So you could have a person who is on hydrocodone who is also hydromorphone positive. So the brand name is Dilaudid or Xalgo, seven times more potent than morphine, onset of action is still 15 to 30 minutes, peak effect 30 to 60, moderate to severe pain, hepatic elimination, no active metabolites, it does cross the placenta and get into the breast milk. So transdermal fentanyl, it requires a predictable flow to the dermal application site. Some people will braid the skin to enhance the delivery system. Anytime a person adulterates the delivery system, it's a concern on my part for a person who has a substance use disorder. So let's say they're on Welbutrin. Bupropion, when it's ground up into a powder and snorted, can actually have significant stimulatory effects. Even some have hallucinatory effects. But the reality is that is a drug of abuse, not a prescribed drug used in the way it should be used. So when the delivery system is adulterated, it raises your suspicion that this is a patient who needs morph services. So when we look at the typical dose of 25 mic per hour, it equals an oral morphine dose of 30 to 60 milligrams, or 6 to 9 milligrams of oxycodone. It takes 8 to 14 hours to achieve peak serum levels. But even if you remove the patch, there's still a reservoir in the subcutaneous tissue that could last as long as 18 hours. Some people, they feel the drop in the fentanyl, and they go into an opioid withdrawal. But there's still detectable fentanyl in the skin over the course of several hours. Absorption is altered when you have fever, when you have broken skin, when you're sweating, and you essentially put water between the pad and the skin, DEMA, and decreased subcutaneous fat. So fentanyl does cross the placenta and get into the breast milk. Methadone, brand name Dolphine, onset of action, 30 to 60 minutes, peak effect in 2 or 3 hours, highly variable duration of action. And that's why I said it's published as 68 hours, but you can have some people who have a half-life that's as long as 96 hours. Very unpredictable and temporally variable on the same person. It is a full muaginist. It is also an NMDA receptor antagonist. It does change the way that 5-hydroxytryptane and norepinephrine are reuptaked. And the QTc prolongation is an issue in regard to all opioids, but more of an issue in regard to methadone and buprenorphine. So if you have a person who has a QT interval greater than 450, you want to be a little bit more careful in the use of both methadone and or buprenorphine. Methadone and buprenorphine actually get into the mu receptor and stay on the receptor. They don't pop off like all the other short-acting mu receptor agonists. And that process requires the occupied mu receptor to be metabolized by the cell. Every 72 hours, you get a new receptor. So the receptors, which coat several cells, are constantly being eliminated. And the morphine and, I'm sorry, the methadone and the buprenorphine are essentially taken into the cell and metabolized. But that's one of the reasons why some people have such long half-lives because of their mu receptor duration. To Pentadol, mu receptor binding is 118th affinity of morphine. It does have a norepinephrine reuptake inhibition. It's from moderate to severe pain. The bioavailability is 32% after the first dose and 97% after the second pass. So there's a significant liver first pass effect. The same thing is true for buprenorphine, by the way. Buprenorphine has a 80% to 90% first pass. That's one of the reasons why it's either sublingual, injectable, or it's subdermal injection long-acting. Now, the problem is that people put the strip or the tab under their tongue and they suck on that and they swallow it. Anything that gets past the distal third of the esophagus goes into the portal circulation and you have an 80% to 90% loss of bioavailability with the first pass. So the key is it stays in the mouth for 10 minutes. They leave it there. They do not swallow the solution until they have the 10 minutes completed. Emerging opioid formulations, abuse-resistant formulations have a physical barrier. OxyContin tried to do that. If you tried to chew the tablet up, it became kind of a styrofoam-type substance. But unfortunately, the way to beat these abuse-resistant formulations and presentations were on the internet within two weeks of the product being released. And so pharmacologic barriers don't seem to have as effective of a way for deterrent. And unfortunately, the majority of people who overdose on opioids have gotten their fentanyl from an illicit area. In Phoenix, the number one place to buy fentanyl is at the gas station. Taper strategies, you want to taper slow enough to minimize the symptoms and avoid signs of opioid withdrawal. My definition of opioid withdrawal is if you have a hole, something is coming out of it. So you're diaphoretic. Your eyes are tearing. Your nose is running. You feel nauseated, and you're vomiting. You're micturating, and your muscles are in spasm, and your joints are sore. Ten percent decrease per week was recommended in the 2016 CDC protocols. Ten percent decrease per month is better tolerated in long-term opioid use patients. Methadone is even slower than that. Sometimes only two percent reduction per week or per month. Rapid tapers are more associated with recent overdose and suspected aberrant drug behaviors. Eighty-nine percent of the Arizona 2016 deaths were associated with rapid tapers. In other words, their prescription for opioids was significantly curtailed, or they were in a place where they couldn't get opioids, typically called jail. And when they got out, they went back to their opioid use. Problem is they had lost their habituation. Consider the medication-assisted treatment if taper is intolerable or if they're pregnant. And pregnancy use with buprenorphine is the standard of care. The U.S. has decreased opioid prescribing by 50 percent over the past eight years, and in the same time, the overdose rates have quadrupled. PDMP monitoring, remember that the pharmacy drug monitoring programs are to help identify multiple users, I'm sorry, multiple providers, early refills, high dosages, dangerous combinations, and multiple pharmacies. Every prescription to every three months, and you need to know what your law is in your respective state. I just do it every time I see a patient, it's very quick. You can actually have your staff get permission from the PDMP to do a check on your members as often as you want. That is not registered under your name, it's registered under your staff's name, but they are allowed to do that in conjunction with you. Practice caution with out-of-state patients who have limited access, and not all the states are visible. For instance, I can see Nevada, Utah, New Mexico, and Colorado, and Arizona, but I cannot see California. So you need to know what your PDMP has as being able to be accessible in other states. Consider medication counts when the patient comes in to see you, and respond to warnings from the PDMP. They will tell you, this patient is also on Alprazolam, 2 milligrams TID from their psychiatrist. And so now that you're aware of that, you have an obligation to provide some intervention, either talking to the psychiatrist or making a change in the opioid load you're giving to the patient. Patient discussion. Discuss information, confirm the patient's aware of all the prescriptions. Form a therapeutic alliance with this member. Review medications and safety risks. MME assessment needs to be done. They need to be aware that there is an association with higher doses and more complications. Reinforce the patient agreement and the monitoring needs. Discuss the care with other providers when appropriate. In other words, don't go down alone. Take all your friends with you. Coordinate your goals with those other providers, such as behavioral health and substance use treatment. Evaluate the possibility for a substance use disorder when there's misuse, abuse, or diversion, and behavioral health supports. You can't find a good therapist that's not worth their weight in gold. You want to have a positive professional relationship that emphasizes their availability to see your patients when you need to have them seen. Stress reduction techniques, cognitive behavioral therapies, relationship counselors, pain support groups, all of these things have beneficial effects for some patients, and you need to find out what would be the best fit for the people you're serving. Talking to others in addition to the provider about chronic musculoskeletal pain can help ease the symptoms of that pain. Practice pitfalls, establish ground rules, stick to them, early refills, Saturday orders. Try to make sure that your patients don't get stuck in that scenario. Naloxone nasal spray should be in the medicine cabinet of every member that's on opioids. Right now, all the AEDs have naloxone spray in them. The BLS course for CPR includes the treatment for opioid overdose. Avoid complete cloning of your charts. We've talked about that before. Do not blindly continue high-risk regimens without a very clear treatment plan that is transparent to you and the patient, and you want to make sure there's justification on those plans. Do not follow early refill or do not fill early refills on a regular basis. I mean, everyone goes on vacation. They may need to have a fill early, but that should not happen on a regular basis. You want to minimize management of high-risk patients without coordination with pain management. In other words, you want pain management, behavioral health, and or addiction medicine in those high-risk patients. Do not have erroneous delays in mail-outs, and this is a real problem we had in the VA. They would mail out the medication the day it would be due to be filled. Well, the problem is that in Flagstaff, we can get 24 inches of snow in one night and no delivery, so you need to be somewhat reasonable in the way that your opioids are mailed out so you don't have delays in reception. And avoid the rapid tapers and immediate discontinuation of opioids, even with something that requires you to say, I don't feel comfortable treating this patient. So they come in, and they say, well, I was at a party, and yes, my drug seems to be positive for cocaine. So that will change your data set in regard to that particular member. It doesn't mean you have to stop everything, but I would have a very short refill, three days, four days, have the patient come back, redo the drug screen, and then continue medications if the patient's back on a therapeutic regimen that is appropriate. Chronic manipulative therapies, especially in chronic pain syndrome. So spine and peripheral structures behave as a interconnected unit. TBI should actually be TB, cervical spine, because the cervical spine actually has a high association to be with chronic head injuries, especially our active duty and veteran population that were exposed to explosive events, IEDs. Myofascial trigger points as a result of poor posture, somatovisceral and visceral somatic reflexes could also be causing significant either peripheral or spinal structure symptoms. Diagnosis and assessment of the 10 distinct regional areas with the TART findings, that's tenderness, asymmetry, restriction, and temperature, and a segmental diagnosis. Assessment of the underlying somatic dysfunction can optimize self-healing, range of motion, activities of daily living, and function. And then OMT is believed to modulate the neurovascular lymphatic chemotactic load on nociception through a central and peripheral set of mechanisms. So there is benefit, and the Cochrane review shows that for spinal manipulation, there is a benefit to the pain population in spine pain. So the role of manual modalities such as OMT has been documented for both acute, subacute, and chronic low back pain. Osteopathic medicine provides statistically significant and clinically relevant pain improvement in patients with chronic pain syndrome with decreased need for prescribed rescue medication. A trial of OMT may be useful. We'd inform consent for this, patients many times who've never had a manual therapy intervention may complain of more pain afterwards, but they should be aware of this and monitor their function after that. I don't use high-velocity, high-amplitude techniques on the neck myself, and I was an Owen Fellow back at Michigan State. There have been a high association of complications from such interventions. Those people who used to use those things need to be aware of the complications and informed consent should be obtained. So what are the controversies as we're closing off? Limits on morphine milligram equivalents. I do not feel that that is a helpful thing, but you know that complication rates tend to rise above 50 and are significant in the research-based peer-reviewed literature above 90 MMEs. So you need to be aware that chronic high-dose opioid therapies do have a higher rate of significance. It doesn't mean that you can't provide someone with that level of intervention if their symptomatology presents with significance. I had a patient who had a 15-centimeter pancreatic pseudocyst secondary to an ERCP. As a surgeon, he was incapacitated with pain, but he was stabilized very well on 180 milligrams of morphine per day. Did well. None of the peer-reviewed issues came up. Everything was great, but the reality was when he transferred to another facility, they would not let him function as a surgeon because of his opioid load. So it's highly variable from practitioner to practitioner in regard to how comfortable a person can be in regard to use of these medications. The waiver is gone now, so we don't have to worry about that. A cost-effective residential care has been highly debated. Average cost to spend a month in a residential treatment center is $45,000. There is significant doubt as to the benefit of this outside of medication-assisted therapy. Sober living homes have had minimal benefit without licensed personnel. Naloxone distribution clearly has improved the survivability of an overdose event. However, those who are rescued with naloxone nasal spray have a very high risk of overdosing again. So the harm reduction of using naloxone spray benefits the member for that particular event, but continued intervention services with medication-assisted therapy is the real answer. Buprenorphine diversion is an issue. Most people divert buprenorphine for the money, but most people keep diverted buprenorphine to treat the withdrawals if they can't get the opioid of their choice. The return on investment for required training has been somewhat questioned in regard to the waiver trainings and things like that. And requirements for board-certified pain medicine consultation for opioid loads greater than 90 mmes has been questioned significantly. Some pharmacies are not filling greater than 50 mmes for patients. Most pharmacies will not fill more than a five- to seven-day supply for a naive patient. So what could be on the boards? Opioid use controversies, conversion process, know the morphine milligram equivalents, support efforts to increase providers able to prescribe medication-assisted therapy. We have achieved that with the dropping of the waiver. We have not seen an increase in the number of people who can access medication-assisted therapy, though. That's been disappointing. Realize that treating the addiction is complex and multidisciplinary. Removing the stigma of addiction is critically important. De-stigmatize the diagnosis of substance use disorder to maximize acceptance of treatment. Realize that this is a moving target. New substances, the fentanyl precursors, are already in Arizona. And the pill process, the pill-making process, is now occurring in the US. So people are coming over with liquid or powder fentanyl to be crushed and made into pills in the US. And enhanced access and availability of treatment programs is really a needed thing. I have some references here, plus you have, in the package, Oliva's study, which is the veterans who had their medication stopped, increased suicide and overdose events. Agnoli's study also has, in a civilian population, civilians who had their medications deeply curtailed or stopped, had a rise in suicide and a rise in overdose events. I thank you for taking this program to become board certified. My name is Tony Decker, and I am available if you have any questions. Thank you very much.

pain

addiction

chronic pain

opioids

substance use disorders

opioid prescribing

non-pharmacologic interventions

opioid tapering

manual therapies

medication-assisted therapy

fentanyl