CDC Recommendations for Nonopioid Treatments in the Management of Chronic Pain

Moderator: Loretta Jackson-Brown

Presenters: Deborah Dowell, MD, MPH; James Robinson, MD, PhD; David J. Tauben, MD, FACP

Date/Time: July 27, 2016, 2:00 - 3:00 pm ET

---

Operator: Welcome and thank you for standing by. At this time, all participants are in listen-only mode until the question and answer portion of the call. If you would like to ask a question today, please press star followed by the number one on your touchtone phone.

You'll then be prompted to record your first and last name. Today's call is being recorded. If you have any objection, you may disconnect at this time. Now I will turn the call over to your host Dr. Loretta Jackson-Brown. Thank you Doctor. You may begin.

Dr. Loretta Jackson-Brown: Thank you Marcella. Good afternoon. I'm Dr. Loretta Jackson-Brown and I'm representing the Clinician Outreach and Communication Activity, COCA in the Emergency Risk Communication Branch at the Centers for Disease Control and Prevention.

I am delighted to welcome you to today's COCA call. "CDC's Recommendations for Non-Opioid Treatment in the Management of Chronic Pain." You may participate in today's presentation by audio only, via Webinar or you may download the slides if you are unable to access the Webinar.

The PowerPoint slide set and the Webinar link can be found on our COCA Webpage at emergency.cdc.gov/coca. Look under latest news from COCA for the July 27th COCA call and select call slides.

Free continuing education is offered for this COCA call. Instructions on how to earn

continuing education will be provided at the end of the call.

CDC, our planners, presenters and their spouses/partners, wish to disclose they have no financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters with the exception of Dr. Mark Robinson. Excuse me, Dr. James Robinson and Dr. David Tauben.

Dr. Tauben and Dr. Robinson would like to disclose that their employer, the University of Washington, received a contract payment from the Centers for Disease Control and Prevention. In addition, planners have reviews content to ensure there is no bias.

This presentation will include discussion of non-FDA approved nortriptyline for the treatment of fibromyalgia. At the end of the presentation you will have an opportunity to ask the presenters questions. On the phone, dialing star one will put you in the queue for questions.

You may submit questions through the Webinar system at any time during the presentation by selecting the Q&A tab at the top of the Webinar screen and typing in your questions. Questions are limited to clinicians who would like information on prescribing opioids.

For those with media questions, please contact CDC Media Relations at 404- 639-3286 or send an email to media@cdc.gov. If you are a patient, please refer your questions to your provider. At the conclusion of today's sessions the participant will be able to:

• State the evidence related to effectiveness and potential risk associated with non-opioid treatment for chronic pain.
• Outline non-pharmacologic and opioid pharmacologic treatment options for various chronic pain conditions.
• Review patient evaluation methods that can be used to identify the most appropriate treatment options for chronic pain.
• And describe the role of patient beliefs and expectations and value of exercise, education, and non-opioid drug treatments and the management of muscular skeletal pain complaints.

COCA is excited to partner with CDC's National Center for Injury Prevention and Control to offer this call series on CDC's Guideline for Prescribing Opioids for Chronic Pain. Save the dates for upcoming calls scheduled for August 3 and August 17. Plan to join the discussions starting at 2 p.m. Eastern Time.

Missed a call? No worries. View call recordings for the June 24 call on the COCA Web page. Today's first presenter is Dr. Deborah Dowell. Dr. Dowell is Senior Medical Advisor for the Division of Unintentional Injury Prevention and Control at the Centers for Disease Control and Prevention.

She previously led CDC's prescription drug overdose team and served as advisor to New York City's Health Commissioner. Dr. Dowell is lead author of the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain.

Our second presenter is Dr. James Robinson. Dr. Robinson is a clinical professor in the Department of Rehabilitation Medicine at the University of Washington. Since 1984, his clinical practice has centered on chronic pain.

Dr. Robinson has published several papers and book chapters on chronic pain. He has served as a principal investigator or coinvestigator for four National Institutes of Health-funded clinical trials dealing with treatment of fibromyalgia and whiplash injury.

Today's third presenter is Dr. David Tauben. Dr. Tauben is Chief of the Division of Pain Medicine at the University of Washington. He has nearly 30 days of clinical practice experience in primary care and internal medicine.

He is board certified in both internal medicine and pain medicine. Dr. Tauben is the Director of Medical Student and Resident Education in Pain Medicine at the University of Washington, jointly appointed in the Department of Medicine, Anesthesia and Pain Medicine.

Dr. Tauben served as a reviewer for the 2016 CDC Guideline for Prescribing Opioids in Chronic Pain. As a reminder, the PowerPoint slide set with the Webinar link can be found on our COCA Web page at emergency@cdc.gov/coca.

At this time, please welcome Dr. Dowell.

Dr. Dowell: Thank you Dr. Jackson-Brown. Today's content is based on the CDC Guideline for Prescribing Opioids for Chronic Pain. Released in March in Morbidity and Mortality Weekly Report as well as in JAMA.

In developing the Guideline we reviewed the effectiveness and harms of non-opioid treatments for chronic pain. Today I'll focus on the treatments for which we have the best evidence.

For more background, you can find this table reviewing reviews of non-opioid therapies in JAMA's publication of CDC's Guideline.

Here is an overview of key findings from the evidence reviews. There is insufficient evidence on whether pain relief, function, or quality of life improves with long-term opioid therapy.

Most randomized controlled trials of opioids have lasted six weeks or less. Long-term opioid use for chronic pain is associated with serious risks including abuse, dependence, and overdose. Many non-opioid therapies can improve chronic pain with less risk for harm.

And when opioids are used, they are more likely to be effective if combined with other approaches. Based on these findings, CDC recommends that non-pharmacologic therapies and non-opioid pharmacologic therapies are preferred for chronic pain.

Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with non-pharmacologic therapy and non-opioid pharmacologic therapy as appropriate.

Effective treatments for chronic pain include non-pharmacologic therapies such as exercise therapy and cognitive behavioral therapy or CBT as well as non-opioid drugs including acetaminophen, NSAIDs, and COX-2 inhibitors, selected anticonvulsants, selected antidepressants, interventional approaches, and multimodal therapies.

In addition to their potential to improve pain and function without apparent risk, non-pharmacologic, non-interventional treatments such as exercise therapy and CBT, have additional benefits including encouraging active patient participation in care and addressing effects of pain in the patient's life.

There is high-quality evidence for reduced pain and improved function, with exercise therapy in hip or knee osteoarthritis, with improvements sustained for at least two to six months. Previous guidelines strongly recommended aerobic, aquatic and/or resistance exercises for patients with hip or knee osteoarthritis.

In addition, exercise can reduce pain and improve function in low back pain, and it can improve global well-being, symptoms, and physical function and fibromyalgia. CBT can address psychosocial contributors to pain, improve function, help patients modify situational factors and cognitive processes that exacerbate pain, and reduce catastrophic thinking.

Access and cost can be barriers to non-pharmacologic treatment. However, aspects of these approaches can be used even when there is limited access to specialty care. For example, a randomized control trial found no difference in reduced back pain intensity, frequency, or disability between patients assigned to group aerobics or to individual physical therapy sessions.

Other low-cost options include brisk walking in public spaces and use of public recreation facilities for group exercise. Even when patients don't have time or resources to pursue CBT with a specialist, some CBT principles can be used in primary care.

For example, encourage patients to take an active role in their care, support engaging in beneficial but potential anxiety provoking activities such as exercise, and support patient coping strategies. Patients with more entrenched anxiety or fear related to pain, or other significant psychological distress, can be referred for formal therapy with a mental health specialist.

I'll now briefly review some of the non-opioid drug therapies for chronic pain. Multiple guidelines recommend acetaminophen for first line treatment for osteoarthritis and for low back pain. Remember to avoid acetaminophen in liver failure and reduce dosage in patients with hepatic insufficiency, or alcohol abuse.

NSAIDs are also first line for osteoarthritis and low back pain. Risks of NSAIDs and COX-2 inhibitors include gastritis, gastrointestinal bleeding, or perforation, fluid retention, interference with platelet aggregation, and renal and cardiovascular risks.

FDA label warnings for NSAIDs note that risks for heart attack and stroke might increase with longer use or higher doses of NSAIDs. Topical NSAIDs have less systemic risk than oral NSAIDs.

Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors or SNRIs are effective and recommended in multiple guidelines for neuropathic pain and fibromyalgia. In neuropathic pain, tricyclics are often effective at lower dosages than needed for improvement in depression.

Remember that tricyclics are relatively contraindicated in severe cardiac disease, particularly conduction disturbances. Start tricyclics at low dosages and titrate up as needed and tolerated. Their anticholinergic effects include sedation, which can be turned into a benefit if pain is complicated by insomnia.

Tricyclics should usually be dosed at bedtime. Selected anticonvulsants such as pregabalin and gabapentin are effective and recommended in multiple guidelines for neuropathic pain and fibromyalgia. Remember to start pregabalin or gabapentin at low doses and increase gradually given dose-dependent dizziness and sedation.

Arthrocentesis and intraarticular glucocorticoid injection can provide short term improvement in function and pain associated with rheumatoid arthritis or osteoarthritis, as can subacromial corticosteroid injection for rotator cuff disease and epidural injection for lumbar radiculopathy. Potential risks include articular cartilage changes in osteoarthritis and sepsis. Rare but serious adverse events have been associated with epidural injection.

Multimodal and multidisciplinary therapies, for example, psychological therapies with exercise, can reduce long term pain and disability more effectively than single therapies. These approaches should be considered for patients not responding to single modality therapy. And combinations should be tailored depending on patient needs, cost and convenience. So how do you choose among therapies for chronic pain?

First, evaluate the patient. Use a focused history of pain and potentially contributing factors and physical exam. Imaging or other diagnostic testing is needed only if indicated. For example, if there are severe or progressive neurologic deficits or if a serious underlying condition is suspected. For complex pain syndrome consider pain specialty consultation to assist with diagnosis as well as management.

The mechanism of pain and diagnosis should inform selection of therapy. For example, although NSAIDs can be used for exacerbations of nociceptive pain such as arthritis or muscular pain, other drugs such as tricyclics, selected anticonvulsants, or transdermal lidocaine are generally reccomended for neuropathic pain.

Physical or occupational therapy can address posture, weakness or repetitive motions contributing to musculoskeletal pain while surgical intervention can relieve mechanical and compressive pain. Glucose control can prevent progression of diabetic neuropathy and immune modulating agents are useful in rheumatoid arthritis.

As with any treatment, use medications only after determining that expected benefits outweigh risks given patient specific factors. Consider falls risk when selecting and dosing potentially sedating medications such as tricyclics, anticonvulsants, and opioids.

Weigh risks and benefits of use, dose and duration of NSAIDs when treating older adults, patients with hypertension, renal insufficiency, or heart failure or those at risk for peptic ulcer disease or cardiovascular disease. And consider topical NSAIDs over oral NSAIDs for localized osteoarthritis, for example, knee osteoarthritis, especially in patients aged 75 or older.

I'll now turn the floor over to Drs. David Tauben and Jim Robinson who will discuss how to apply these principles in the management of chronic pain.

Dr. Tauben: Thank you Dr. Dowell. I'm very pleased to be sitting here with my colleague, Dr. James Robinson. And we will proceed with a clinical case discussion. The learning objectives are listed here. We will outline a differential diagnosis.

This particular real life patient, symptoms and the methods chosen, among them to establish a diagnosis. We'll spend a bit of time on patient belief systems that might interfere with treatment and the strategies to manage these, the role of patient education in setting expectations, we describe the rationale as reiterated to some degree for exercise therapy in this particular case, and how to overcome barriers that may arise in physical therapy. And then we'll defend the rationale and discuss a bit more about the use of tricyclic and other antidepressant drugs as initial management for this patient.

So I will move this forward on our slide to patient history, slide 34 for those keeping up. Dr. Robinson, please proceed.

Dr. Robinson: Hi, this is Jim Robinson and the way we're going to divide things up is that Dr. Tauben is going to discuss general issues that are raised by this patient. I'm going to discuss the specifics of my interactions with this patient.

This is a patient whom I've seen. If fact the dates that are given are real dates. These are the times that I saw this patient. I first saw this individual on July 8, 2014, a 38 year old man who presented nominally with neck pain which was quite diffused but he also had multiple other symptoms including pain all the way down his spine and diffused pain in both upper extremities.

He had actually, although he reportedly was symptomatic for a few weeks, he actually had intermittent symptoms dating all the way back to six years earlier. He had undergone and electromyographic study at the time which was negative. He had been, had undergone an MRI scan of the cervical spine ordered by his primary care provider three weeks before I saw him.

I reviewed this study and just to say, he did not show compromise of neural elements as expected. It showed some degenerate changes. Could we have the next slide please? So more on the history. His primary care provider has prescribed Percocet, for him and he was taking two tablets per day. Also Cyclobenzaprine.

Asked him about his mood and wanted more information about that. He described himself as grumpy. Past medical history was noteworthy in this male patient in that he had a history of irritable bowel syndrome and that connects with what we'll get back to.

Smoked a half a pack of cigarettes per day. Denied use of illicit drugs. And there's no evidence or everything else that he was using drugs. He lived with his girlfriend and ten year old daughter. He was working in a rather physically demanding job building cranes and he was missing one day of work per week. And he was spending three hours after work when he did work, at home resting. Very important issues related to work disability.

Next slide. And turning it over to Dr. Tauben to talk about how we might assess such a patient.

Dr. Tauben: Okay, so I'll speak a moment about some very key primary care centric tools to offer your patients as patient reported outcome measures. And I will follow this slide that holds forth, you'll see in a minute here on this one. The specifics on the P-E-G tool or the PEG tool.

The PEG tool has been validated against a number of these and mirrors the pain inventory Promise 10, the Oswestry, and the Roland-Morris Disability Questionnaire. So it's a three question item.

Reference to mood, I have found and I think many of you will ask your patient how they're doing and they'll use a word like grumpy. Or they might say, well, if it wasn't my pain I might be happy but, you know, it makes me anxious.

But we feel and guidelines support the use of evidence based more objective granted they're subjectively submitted. But validated tools such as the PHQ-9 for Depression or for Generalized Anxiety Disorder, the GAD-7. There's a short version which I will describe in a moment called the PHQ-4 which I would strongly recommend for all primary care providers.

And if these measures of distress are elevated a full PHQ-9, GAD-7 in addition to the PHQ-4. And with high degrees of distress, the primary care post traumatic PTSD screen, PC-PTSD, very, very useful based on the high incidence of PTSD in a highly distress patient population.

Screening for alcohol use disorders such as the AUDIT-C, the ORT, SOAPP, COMM or DIRE are also useful though validation by grade, quality of evidence is not strong for these. And, of course, prescription drug monitoring programs, one of the most important things to check because this patient may request an opioid refill. We shall see.

Next slide. In the CDC Guidelines, the specific tools that I identified are highlighting here. The PEG on the left is a screenshot from Dr. Krebs and Kroenke's article that shows on a zero to ten score P stands for pain, zero to ten. What number best describes your enjoyment of life in terms of pain interference. Ten is completely interferes. Zero it does not interfere, and similarly for general activity. Pain, enjoyment, general activity. That's the PEG.

Great questions. It takes less than 11 seconds for your patient to fill these out. The PHQ-4 I've identified here. Again, a very quick screener for psychological distress. As you can see the top two questions are from the GAD-7. They're the anxiety questions and the other two are the top two questions from the PHQ-9.

Again, scoring halfway up or approximately, since the total score could be twelve, so a score of six or more, really requires attention and addressing this in order to proceed with effective management. So Dr. Robinson, next slide.

So I understand you did conduct this report.

Dr. Robinson: Yes. And this gives you the data for this individual patient. Notice first the pain diagram, upper right-hand side showing the widespread pain. His entire neck was painful and he had that in red as the worst area of pain.

Pain intensity six over ten. Pain interference was, general function seven over ten with quality of life seven over ten. Interference with sleep initiation and sleep maintenance, six over ten.

Mood sort of on the fence, PHQ-4 of six. Follow-up GAD-7 and PHQ-9. Sort of midrange. Very importantly, this individual said the most important activity that was bothering him was work. Gave an eight over ten rating with the difficulty he was having with that. He was missing a day of work per week. It was very important.

His Oswestry Disability Index was 50. Opioid Risk Tool was 4 because he did not appear to have a high risk of abuse. Satisfaction of treatment was low. Moving on. Next slide, next. Upon physical examination, he was 5 foot 7 inches in height. Weight was 119 pounds. Very thin man and he reported that he was 10 or 11 pounds below his normal weight.

Vital signs are normal. He had at least 14 of the 18 tender points that were used in the 1990 American College of Rheumatology Criteria for the diagnosis of Fibromyalgia. Limited range of motion in his neck and his lumbar spine with no particular pattern. Neurologic examination was basically normal. Some pain inhibited weakness in upper extremities but not in the same neck distribution. Next slide please.

So my diagnoses based on my initial examination was that his main problem was an axial cervical spine problem. Often we're not able to identify a precise generator in this situation so we use terms like non-specific axial pain. His widespread pain, he met criteria for Fibromyalgia which is unusual in males but he did. I also was concerned about the possibility of something more sinister like an inflammatory arthritis.

He had unexplained weight loss and just to follow-up, his weight did return to normal when we started treating him. So put that one off the list. Long term opioid therapy on a low dose but still a question of how to address that. The irritable bowel syndrome which goes with Fibromyalgia. Mild depression and anxiety. Moderate sleep disturbance and not on the list, very importantly threatened work disability.

He was making it to work but was missing time. So next slide please. I'm turning you over to Dr. Tauben again.

Dr. Tauben: Thank you Jim. So I presented here on slide 41 two images. And the top right is Dr. Dan Clauw's excellent article review from JAMA last year on Fibromyalgia diagnosis. And this is the current widespread pain index that he's recommending. This doesn't even require a tender point exam although I personally, and I believe Dr. Robinson would agree, touching a patient matters a lot to them.

And it matters a lot to me to identify what their verbal report and their actual physical report. But your patient could just fill out this questionnaire, a couple of minutes, locating the number of body sites that pain is present or that they report. And then severity. And this includes fatigue, troubled thinking or remembering or waking up tired or unrefreshed against scoring those points in zero to three.

And then pain or cramps in the lower abdomen. Dr. Robinson described briefly the irritable bowel syndrome. There's been a lot of work identifying co-occurring multiple pain conditions. So if a patient has more than one difficult to accurately diagnose chronic pain disorder such as functional bowel disease, irritable bowel syndrome, interstitial cystitis, temperomandibular disease, tension headaches, and chronic pelvic pain syndromes, these patients often are also going to screen positive on both the widespread pain index, the symptom severity index, and also on the left is a fibromyalgia-ness score which is becoming increasingly popular.

It's an awkward term. Dr. Fred Wolfe introduced this term. What it represents on the symptom intensity, the bar at seven and according to their scale at the time represented the diagnosis of Fibromyalgia. But the middle bar at the top of the bell shaped curve there, represents the average. And as patients move up the symptom intensity scale they may meet criteria for Fibromyalgia.

But the important point I'm trying to make is that as this symptom intensity scale increases there is a correlating increase in the likelihood of poor outcomes from a whole host of interventions including surgery. Also including the procedures that have been identified.

So without identifying the likelihood of co-occurring pain diagnoses which can be derived from the history as well as a symptom intensity score and I'm recommending the Fibromyalgia score that Dr. Clauw has here. Again it's referenced on our list here for you. It's very useful strategy.

And one or two make a more comprehensive diagnosis of your patient. So next slide.

Dr. Robinson: Okay. And now it's back to Jim Robinson and what I actually did in my initial plan with this individual, first to discuss what might be going on. And I focused on the fact that he had multiple symptoms and I said this could reflect an inflammatory or autoimmune process and we'll look at that.

But also it could reflect something like Fibromyalgia. I basically wanted to setup reasonable expectations for him to get appropriate records. I did order laboratories just as a screen. And the question, what is appropriate rheumatologic screen I'll leave to the rheumatologist.

My screen was a C-Reactive protein, an acute-phase reactant, an Anti-CCP to check for rheumatoid arthritis because he did have problems in his hands and ANA. I then actually got him information on Fibromyalgia which is very interesting because he came back. Next slide.

Came back two weeks later and he said, I don't like that diagnosis. It's a psychological condition. He got on line and I had to talk him down. And this was, you know, a challenge with our patients. Many of our patients, a term used by a historian once was a great term, a lust for Organicity. And when you give something to them, they suggest it's a psychological diagnosis, this patient was incensed.

So we discussed the idea of central nervous system sensitization and so on and so forth and was able to get him to at least accept walking down the path, this could be Fibromyalgia. By then the laboratories had come back and all was normal so there was no evidence of an inflammatory or of autoimmune process.

So I refereed him to physical therapy for basically range of motion exercises and strengthening of the neck and shoulder girdle muscles and also while I could say more on the physical therapy part, let me go onto the next slide please. And this a hard slide to summarize.

In my mind, physical therapy is wonderful. This is the closest thing to a wonder drug. This is from the New York Times, June 20, 2016. But exercise is really I think the most effective approach to muscular skeletal pain of many kinds and it's been validated in research.

The problem, and we won't be able to spend much time on this, the problem is often our patient are resistant to exercise therapy. We hear over and over again at the pain center, the physical therapy made me worse. So we have to think and be very active as clinicians on how to make physical therapy succeed.

We have to work with physical therapist who are willing to work with chronic pain patients. A lot of physical therapists want to do just sports medicine and will not work effectively with these patients. We need to be very actively involved. Recheck the patient after they start therapy. Ask them about their therapy. Have them demonstrate their exercises.

We need to educate our patients about basic concepts in exercise therapy such as baselines and exchange lists, which means different exercises that accomplish the same biomechanical goal. The notion of tolerance for flare-ups, what do they do when their pain gets worse. All of these things have to be addressed in order to make exercise therapy effective.

Next slide please. So for this individual, remember I said two slides ago that we, I, referred him to physical therapy. I had him discontinue his Cyclobenzaprine in favor of starting Nortriptyline which we'll talk more about in a second.

And we would plan to titrate him up to 50 milligrams at bedtime which is the dose that I often use as at least an initial stabilizing dose. The opioid issue was resolved without any help from me. The patient's primary care provider had left his practice so the patient no longer had opioids. So end of the opioids. That's the easiest ending of opioids you'll ever find but that's how it happened. Next slide please. And this goes to Dr. Tauben.

Dr. Tauben: Yes. Thank you, Jim. I wish I had more of those patients just because managing opioid discontinuation. But he was not on a large done. And just to comment here, the engagement in which you were able to achieve with the patient, I want to highlight that as a critical component in establishing the relationship between you and your patient, that it's much more powerful than writing a prescription.

Dr. Robinson: And what I did, do with patients like this is I said, let us walk down this path. I know you think I'm pretty crazy to suggest Fibromyalgia but let's take a couple of steps and you'll see what happened when we did that.

Dr. Tauben: Okay. So we're now on slide 46. Why Nortriptyline? Why tricyclics and why the SNRIs? I'm going to call out the N in the SNRIs which is norepinephrine, reuptake inhibition. And tricyclics are predominately norepinephrinereuptake inhibitors. SNRIs are less so.

And evidence strongly supports that norepinephrineis the principle neuro transmitter that up-modulates increases the potency in an individual of the most important system of pain in the human body, the descending inhibitory pain system.

And in the diagram here that I borrowed from Milan, you can see there in red going on the left are the input into the central nervous system, the sites where the noxious stimulus occurs.

And then from cortical periaqueductal grey, Rostral ventromedial medulla in the brain stem and in the dorsal horn, strong evidence that up modulation of norepinephrine sensitive neurotransmitters produces a robust response in not only neuropathic pain but also Fibromyalgia. Next slide please.

The data supporting this continues to be robust. This is a few years old. But for post herpetic neuralgia numbers needed to treat well over two. Diabetic peripheral neuropathy almost every patient, atypical facial pain. This is not trigeminal neuralgia but other atypical facial pain syndromes which were reviewed.

One out of three will have 50% improvement and look how beneficial these drugs are in fibromyalgia. Numbers that treat, one out of two.

((Crosstalk))

Dr. Robinson: Moving on, again, I got the patient started and he was willing to walk down this path and said I'm willing to try your drug even though I don't think I have a psychological condition, et cetera. Came back August 27th, this is about a month later and said things were substantially better.

Medication Nortriptyline and the physical therapy were very effective. He became absolutely in love with Nortriptyline as time went on. His pain had reduced somewhat. His functional impairment had reduced. He was sleeping better. On examination, he had few tender points and not mentioned on this slide but very importantly he was now working every day of the week.

So substantial benefit and he became a convert. We never had another argument about whether he had Fibromyalgia. He said yes, this works, Came back about a month later and there were problems with Nortriptyline. It's not a simple drug.

He was having morning fatigue, dry mouth. We had to kind of walk through what to do about that. With some discussion he basically said, we'll stay on this same drug, the same regiment. And again, his pain parameters were improved. Although he was still struggling with pain, his functional activity had improved. He was working on a regular basis.

And then onto Dr. Tauben.

Dr. Tauben: Okay, thank you Jim. So next slide. It's slide 49. So Dr. Dowell mentioned a non-drug and/or multi modal analgesia. And I listed here again and to reiterate for the sake of time, we'll fly through this.

But cognitive therapies, very simply, identify the distress and the negative beliefs and behavioral approaches. When you combine the two you get cognitive behavioral. And it includes mindfulness, relaxation, and biofeedback strategies. The physical activation which was described in detail by Dr. Robinson.

Never forget the spiritual and this is identifying and seeking meaningfulness and purpose in one's life. And this is a very important discussion to have with your patient. If it's all about pain, nothing else matters and that's the ten over ten score. In the Department of Defense, zero to ten anchor.

If nothing else matters but pain, you're not going to make any progress. Something else more important than focusing on pain is critical. And then education, right. We can see the value in this patient. Many situations require family involvement as well so they're on board and not advocating for the wrong care or disabling the patient worse.

So next slide and we're wrapping this up in just a few moments. This complicated slide is my best effort to extract from multiple different studies that often have low grade, G-R-A-D-E, grade quality of evidence. Most studies also are less than four months which does not represent chronic pain and rarely do any of these studies compare one treatment to another.

The CDC Guidelines list these studies and Dr. Dowell presented the evidence as well. But if you take a big picture view and recognize that this is not a comparative effectiveness but one comparing, you see that opioids really don't win any prizes here and that tricyclics and the SNRIs are at least as equivalent and certainly less hazardous.

Anticonvulsants drugs which we did not spend time here, Gabapentin and Pregabalin particularly, about 30% improvement. Different mechanism than the tricyclics. Acupuncture at least 10%. Cannabis up to 30%. Again low quality studies they're continuing to flood out there. But it does offer benefits.

Cognitive behavioral therapy mindfulness, well into the 40's. Now this is various pain outcomes. This was pain annoyance. I believe it was Churkin and Turner's study recently published in JAMA. Up to 40 plus percent improvement in back pain with a mindfulness training program compared to a CBT program.

Mindfulness lasted longer and I never had a case reported of overdose of mindfulness yet. So we're looking for that case report as necessary. Graded exercise therapy, very difficult to evaluate. Getting patients to sleep is critical. That's another advantage of the tricyclic antidepressant drugs because not only do you get moods, not only do you get pain, but you get sleep benefits.

And call out to our antipathetic and chiropractic colleagues, manipulation therapy has been very effective. Again the ability to rank this. The rating system I have here was limited but there is certainly a positive effect. So next slide and we're ready to wrap up here. Dr. Robinson.

Dr. Robinson: All right. And I last saw our patient on September 25, he comes back on November 5. Now he's got increased pain. Oops. That's when I go over the exercise program in detail. Have him demonstrate his exercises.

Turns out he was doing basically stretching exercises no strengthening. I think the literature supports the role of strengthening for neck and shoulder girdle muscles. He was having problems with sleep so we discussed the use of Trazodone or more Nortriptyline.

He came back on February 10, 2015. By the way his weight was up to 140 pounds. Nortriptyline tends to get people to gain weight. e did great. We actually had to, we tried him up on Amitriptyline briefly. He didn't like it. We went back to Nortriptyline. We also gave him a strict trial on Trazodone.

When I saw him on February 10, 2015 he was having worse symptoms in his left upper extremities. I was concerned about a possible C-6 Prolotherapy based, his neurological exam was difficult to interpret. I won't give you all the things that happened but I have to say a couple more things that are not on the slide.

And one is that he continued to do well on Nortriptyline over the next year but did have some concerns about his work. And we have now been talking about he needs to change his job because his job is continuing to flare-up his neck. So making, going to summary, when you get...

Dr. Tauben: Next slide please.

Dr. Robinson: This is next slide. Thank you. In our complex patients, we have to anticipate, there will be multiple symptoms. We have to be prepared ourselves for ups and downs and they have to be prepared. The worst things that we see with many of our pain patients is that they do well until they have a flare-up and then everything falls apart.

We have to set reasonable expectations. For example, that they will have ups and downs. We have to continue to reevaluate them. We have to consider psychosocial factors and in this instance, actually the patient's irritability resolved quite well when he got onto the medication.

But we had to deal with his belief system. If that had not been effectively done, we would have gotten nowhere. The big problem with pain management is it takes time and with the busy practices that we all have, it's so difficult to look at all the domains that are relevant to a patient's pain. But if we don't do that we often lose the game.

Dr. Tauben: All right. Thank you Jim. So I'm going to just identify we have a long list of references. Scrolling through, moving this slide deck, we've lost our ability to move the slides but there are a long list of references that are available to you.

And so now we'll move to slide 59 to ask a question. And with this, I'll turn this back to our Centers for Disease Control Prevention team. So back to you all.

Dr. Jackson-Brown: Thank you presenters for providing our COCA audience with such a wealth of information. We will now open up the lines for the question and answer session. Questions are limited to clinicians who would like information on prescribing opioids.

For those who have media questions, please contact CDC Media Relations at 404-639-3286. If you are a patient, again, refer your questions to your healthcare provider. When asking a question, please state our organization and also remember you can submit questions through the Webinar system. Coordinator?

Operator: Yes Ma'am, thank you. If you would like to ask a question over the audio lines, please press star followed by the number one. You'll be prompted to record your first and last name. Please check that you do not have your mute button on when recording so that I'm able to hear your name and introduce you.

If your question is asked and you want to withdraw your line from the queue, press star followed by two. Once again, press star one and record your name. We do have questions coming up and I'll get the first name.

Dr. Jackson-Brown: And while we're waiting for the first question from the coordinator, so...

((Crosstalk))

Operator: Morticai Potash.

Morticai Potash: (Unintelligible).

Operator: I'm sorry. Go ahead.

Morticai Potash: Yes. Hi. This is Morticai Potash calling from Tulane University. Just have a question for the speakers on the presentation on the cannabis data. I know it's not as old as the opiate data. It seems that it has around the same response rate as opiates. And I know that the medicinal use of marijuana is increasing. You know, one concern that I have is that we're ignoring some potential for harm in the same way that we ignored the potential for harm with long term opiates in the 1990s.

And additionally there was just a recently publication in the Journal of Neurology about increased risk of stroke as well as increased use in adolescence in Colorado. I'm afraid that the same kind of paradigm that blinded us to the risk in 1990 is happening now.

Dr. Robinson: Dr. Potash, this is Jim Robinson. And so I gather the question has to do with possible risks of cannabis. It's very interesting. You have a more current data than I do. I reviewed this literature a year and a half. Looked at 31 randomized controlled trials in cannabis and concluded that there is a modest effect in a number of pain states and did not find serious toxicity associated with cannabis in the let's say medical realm.

There is something called an Emesis Syndrome that people will start after they've used cannabis for a while, start vomiting quite a bit. That was the only medical downside that I saw and but there were significant risk of psychiatric problems.

When cannabis is used on young people there are serious associations with failure to complete their education and so on. A study in Scandinavia followed military recruits who had been exposed to Cannabis and found that their prevalence of psychiatric hospitalization within ten years was substantially higher than non-users.

So I am concerned about the mental health aspects of cannabis. I did not find evidence that it is a serious problem in terms of organ toxicity. But that was why...

Morticai Potash: What I'm talking about is the publication in the Journal of Neurological Sciences about marijuana use and acute Ischemic stroke in the latest issue of Journal of Neurological Sciences with an accompanying editorial by the Journal's editor.

So what I'm saying is, you know, I'm worried that the evidence is not all in and we're not learning the paradigm lessons from the 1990s that, you know, it takes a while when we become more supporters or encourages of a type of treatment to see the problems that emerge in a population.

Dr. Tauben: Dave Tauben. I was just going to jump in. You know, your point is well taken. We've starting another epidemic, another way to seek relief without using well proven and non-pharmacologic strategies. The topic today, the focus and there's, we have a full series that we plan. We'll go into this in more detail.

But the topic is, how do we not only do we avoid non-opioids but how do we avoid non-pharmacological strategies? And I think going to the non-pharmacological strategies as iterated in recommendation number one, is strong and powerful. Just remember that the placebo effect is about 40^%.

And if you recall the table, it was only sleep and mindfulness that did better in terms of improving pain function. And those again are non-pharmacological strategies. So if we can train our patients to turn on their own endogenous systems, particularly the descending and inventory pathways, that's great. Thanks for the feedback. Let's get to some other questions.

Dr. Tauben: Just one last thing. I think your connection with the 1990s and opioids is great. I was around in the 1990s and everybody was saying how benign opioids were and we learned very differently.

Dr. Robinson: Yes.

Morticai Potash: Me too. I really drank the Kool-Aid in the 1990s.

Dr. Robinson: We all did.

Dr. Tauben: All right. You're right. And that's why we're having this conference and why it's such an important issue now. Because just because we did things one way recently does not mean we need to continue to do that. And it's the paradigm shift that's grinding our patients, grinding our health system and really making it a challenge to be an effective provider.

Why don't we get another question? That was a great question, Dr. Potash. Thank you.

Operator: Thank you.

Dr. Jackson-Brown: Operator, do we have another question from the phone?

Operator: And if anyone else wants to queue up, again it's star one and record your name. Next we have Fred Goldstein. Your line is open.

Fred Goldstein: Yes, thank you. Dr. Goldstein from Philadelphia College of Osteopathic Medicine. Just a couple of quick points. One, I'm happy to see my former graduate student, Michael Osssipoff who is cited in the Nortriptyline study.

He actually started some research with me way back. Second quick point. In Pennsylvania, the medical marijuana law is now approved and there's been encouragement to do marijuana research so I hope to get involved in that.

My question is on slide 22 on Acetaminophen, it said it can be hepatotoxic if greater than three to four grams per day. And I guess I'm referring to the FDA recommendations that for basically all patients, we really not go above 3000 milligrams per day. Any comments on that?

Dr. Tauben: So I'll step in but Dr. Dowell, you were presenting that data. I actually am very cautious with Acetaminophen. I think three to four grams in someone who does not use alcohol is reasonable but so many people do and don't provide a reliable history.

And, you know, with previous liver disease, Hepatitis C in particular, it's a caution. And in my view prescribing based on my clinical experience and extended review over 30 years of practice, for patients over 60, I restrict to 2 to 2.5 grams a day.

I think the challenge is people take a lot of Acetaminophen over the counter. We fail to ask that question, what else are you taking over the counter. We get vague answers in response and we often prescribe opioids in combination with Acetaminophen and that just adds to the overall problem.

So even, you know, NyQuil has Acetaminophen in. And so being careful about Acetaminophen is I think the strongest point. Dr. Dowell, I would like you to step in, if you'd like to.

Dr. Dowell: Sure. Just briefly. So, you know, the labelled instructions used to be four grams per day, or lower dosages for patients with chronic alcohol use or liver disease.

In the last few years, one of the major manufacturers has voluntarily reduced their label instructions to three grams per day and I think we're moving towards increased caution in part because of the reasons that Dr. Tauben mentioned. Patients are getting acetaminophen from other sources and other over-the-counter drugs. Sometimes a combination of over-the-counter drugs. They don't even know they're taking acetaminophen.

So I agree. It's prudent to be cautious and only, you know, use the lowest amount that you need.

Dr. Robinson: Just let me jump in. Your question opens up an additional array of questions. So the value of Acetaminophen in chronic persistent pain is difficult. There's very little literature. It's not been studied if at all to my view.

And we're talking more than three months or six months. This is years later. So one of, my most important aspects as a safe provider is to periodically withdraw patients off medicines that they've thought to be helpful, that we being to wonder if it is making much of a difference.

If there's active nociception, i.e., pain coming in from a tissue injury, i.e., an active osteoarthritis, that might give an argument for NSAIDs which were mentioned or Acetaminophen which was mentioned.

If we're not clear where the pain is coming in from, like headaches, we know that Acetaminophen causes rebound headaches and therefore does not offer much of anything.

And again, taking patients off drugs that they don't need is as good as my, we can do, one of my most effective therapies is subtotal or radical medicine-ectomy procedures that when they show up in the clinic to really remove useless agents.

But thinking of the low toxicity drugs are not free of toxicity and are said to account for 25% of the overall reported adverse drug side effects internationally. Now granted they're very widely used but they are not free of side effects, often not affected the non-active Nociceptive pain syndrome. Similar for Acetaminophen.

Fred Goldstein: Okay, thank you.

Dr. Robinson: Pleasure. Thank you for the question.

Operator: Thank you. Next we have Dr. John Divine. Sir, your line is open.

John Divine: Just a question about PTSD in chronic pain and how it's important to screen for that and treat. What do you find is the best way to intervene or treat PTSD especially in a patient unable or unwilling to seek mental health professional's care?

Dr. Tauben: Fabulous question. I'm going to star first. Dr. Robinsons has a PhD in Psychology. He'll step in in addition to this. So the first thing is you're identifying it. And I've a very low threshold. I like the opioid risk tool. I know it's not well validated but it does ask a sexual abuse question.

I disagree that it doesn't give three points to men. Just gives it to women. Woman have a higher likelihood to preadolescent sexual abuse but that at least asks something relevant to PTSD. I think the adverse childhood experience sequence that we learned about, the exposure to violence in the home, family members abusing drugs, family members incarcerated, abandonment, these are key questions that we have to ask.

So I'd trigger a PTSD screen with any evidence of distress not by asking the patients but by screening with a PHQ-4 and then a PHQ-9 and a GAD-7. We did a survey in our clinic, it's a tertiary, quaternary clinic of the University of Washington on a 1200 consecutive new patient referrals. And it's not published yet.

Then we're doing more data analysis. But PTSD was represented in almost 30% of our new patients that had not been previously diagnosed. So make the diagnosis at the four question screen is great. If you can't remember them just ask, do you have nightmares? And do you startle?

If those two are positive, you're halfway there. The others are even harder. But that's a great - so what do you do to get them to recognize that most people thank me for making the diagnosis because they themselves recognize this. I get people who say this is the first time anyone identified this as a problem. So I'm thinking, much of the time, it's embraced by the patient because they're really struggling with ideas and concepts they haven't had before.

The treatments and I'm going to ask Dr. Robinson top get into it a bit further with the evidence based PBT and DBT, et cetera. But the treatments, evidence based SSRIs or SNRIs or TCAs. They're mostly studied in SSRIs. But they're useful.

And we typically use Prazosin which is an off label use, and I'll specify that now but it was identified as very effective in veterans and its first line therapy. We titrate two milligrams up to five or ten milligrams targeting nightmares. And it has been a very effective drug. That to me is the hardest drug to get our patients to come off of versus the others because it gets such dramatic relief cautioning them about the risk of hypertension because it's an antihypertensive drug.

Jim, more comments. It's a great subject to talk about.

Dr. Robinson: Yes, well, it's wonderful. And I have to tell you Dr. Devine, we have been educated by the psychiatrist who participates with us on a panel who has absolutely noticed this again and again. And so we are all more sensitized to PTSD.

Dr. Tauben: And you'll be speaking, by the way, at the next...

((Crosstalk))

Dr. Robinson: Yes, with Mark Sullivan.

Dr. Tauben: Yes.

Dr. Robinson: Waiting just to hear, probably talk about that. I would say just another piece on this, that what we often see as a lot of avoidance learning in our patients. If we don't, even if we don't call it PTSD, people are traumatized often by their pain and so they have a have a huge avoidance of pain.

They will not gauge an activity that they think might be painful. Back in my days as a psychologist. I was involved in the broad area of avoidance learning. I think PTSD is a subset of that but our patients are very avoidance. I will move on. It's a wonderful question but we have to give more time to some more questions.

((Crosstalk))

Dr. Tauben: We have to give time back to people's busy clinics which you're probably backlogged on in your office if you're a practicing clinician and also to respect your time.

So this question's going to come up in detail with Dr. Sullivan at a later session as I understand. But at this point let me return it back to our Coordinators at the Center for Disease Control for wrap up.

Dr. Jackson-Brown: And before we wrap up, I do want to ask the presenters a question that came through the Webinar. And part of the comment is that the case study presented kind of made it look a little easy if you will for you all to manage that pain.

And so the questions coming in from the Webinar are for more difficult patients like sickle cell patients where there's maybe some more resistance. Do you think that these strategies will still work?

Dr. Tauben: Great and you know, what, Dr. Robinson and I were challenging whether we go to the hardest or the most straightforward and we actually elected a very common practice presentation that on the front end should be recognized.

So specifically, a sickle cell, sickle cell is, the pain with sickle cell is active, Nociceptive. It's infarction of body organs, bone, liver, spleen, lungs and this is an opioid based therapy, I would say acute sickle cell management.

But on the other hand between sickle cell flares, if the patient is doing relatively well, this is an overwhelming condition and they'll be high degrees of distress and persistence of chronic pain in this setting may lead to sensitization and associated co-occurring pain disorders.

So the overlap between severe Nociceptive disease, sickle is an excellent example. Let me call out inflammatory bowel disease, lupus, active accelerated inflammatory joint disease. These are often seen in our practice and these adjunctive therapies can be added and act as the floor to which you strive between flairs of those disorders.

And active management of disorders is much more successfully accomplished. But the ruling out, non-drug and non-opioid pharmacologies based on the disease I think is a mistake. We use those also. Jim.

Dr. Robinson: Yes, I would just like to say that this is what gives Dr. Tauben and I grey hair. And Dr. Tauben lost most of his hair. And that is that as pain physicians we are put in the situation of addressing multiple, multiple problems, some of which we know very well the path of physiology, some of which we don't.

And it's just extremely difficult. I picked spinal pain because I work in the spine clinic when I'm not in the pain center. But there are so many disorders and sometimes there is active nociception. And sometimes it's more of a central sensitization problem and we have the very difficult challenge of trying to sort those out.

Often in diseases that we don't now as well. Dr. Tauben can speak with great expertise on sickle cell disease because of his background in internal medicine. But we run into pelvic pain and we run into people with pseudo tumor cerebri and on and on and on. And it just makes things difficult. That's why it's challenging to be a pain doctor.

Dr. Tauben: Yes. But that's challenging I think for primary care doctors with an understanding of what's your diagnosis and Dr. Dowell stressed that early on. Make the diagnosis and chronic pain doesn't fly. It's, what's the underlying presumed diagnosis, as best you can make and list all the others because you're likely to find sleep disorder.

You're likely to find deconditioning. You're likely to find inability to work. Disability. You're likely to find distress, depression, anxiety, and PTSD. And none of those that I just outlined are managed with opioids. In fact, opioids impair recovery in all those domains and really play no role.

So it is a good topic and I fear that we're out of time. But stay tuned with the CDC COCA series because they'll be more to come so thanks very much. Do we have any more questions to take?

Operator: There were no more questions in the queue, Sir.

Dr. Tauben: Great.

Dr. Jackson-Brown: And so on behalf of COCA, I would like to thank everyone for joining us today with a special thank you to our presenters. The recording of this call and the transcript will be posted to the COCA Web page at emergency.cdc.gov/coca within the next few days.

Free continuing education is available for this call. Continuing education for COCA calls are issued online through TCE Online, The CDC Training and Continuing Education Online System at www.cdc.gov/tceonline.

Those who participated in today's COCA call and would like to receive continuing education should complete the online evaluation by August 26. Use course code WC2286. If you're going to be listening to the recording of this call after August 26 but before July 26, 2018, use course code WD2286 to earn continuing education.

To receive information on upcoming COCA calls mailing list by going to the COCA Webpage, emergency.cdc.gov/coca and click on COCA mailing list. And remember save the dates. The conversation will continue. On August 3 we will have the next series in this opioid COCA call series. Join us at 2 p.m. And then mark your calendar for August 17 for the final call in this series. We will be discussing dosing and titration of opioids.

For the latest updates about Zika from CDC, well join us on Tuesday, August 9 starting at 2 p.m. Eastern for an update on CDC's interim Zika virus clinical guidance and recommendations. More information can be found on our COCA Webpage, again at emergency.cdc.gov/coca.

CDC does have a Facebook page for clinicians to receive COCA updates. Like our page at facebook.com/cdcclinicianoutreachandcommunicationactivity.

Thank you again for being a part of today's COCA call. Have a great day.

Operator: This will complete today's conference call. Thank you for your participation. All parties may disconnect at this time.

END