Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine CME Conference March 10-13, 2016

Transcription

1 Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine CME Conference March 10-13, 2016 Disclosures: Fibromyalgia Update Wayne Blount, MD Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices.

2 The Chronic Pain of Fibromyalgia B. WAYNE BLOUNT, MD, MPH JenCare 1 Disclosure The speaker has no conflict of interest, financial agreement, or working affiliation with any group or organization. 2 Objectives Definitions Pathophysiology Fibromyalgia Summary Extras : lots 3 1

3 New Patient 56 yo w female c/o chronic, unrelieved, diffuse pain X 8 years. PMH: Insomnia & migraines Her last doctor had her on lortabs : 10/650 mg, 1-2 q 4-6 hrs and xanax 1 mg TID. She just moved to your state & town because Medicaid is easier to work with here. She has brought with her an old (4 yrs ago) CT scan to prove she has real problems. 4 What do you do? Start from scratch!! If the patient is unwilling to do that, that, in itself is a red flag that there might be drug seeking. An approach to such a patient 1 st? Define what you re working with 5 What is Fibromyalgia? A clinical syndrome of widespread muscle pain : Chronic, Non-inflammatory, with Fatigue & Tender points Extremely common pain phenomenon occurring in a defined pattern 6 2

4 More on Fibromyalgia Prevalence 1-12% All ethnic groups All nations Increases with age Women 4-7 X more at risk 7 Signs & Symptoms Insidious in onset Diffuse soft tissue pain Pain increased in A.M., with weather changes, anxiety, & stress Pain improved by mild physical activity or stress reduction Non-restorative sleep: reduced sleep efficiency of 75% 8 Signs & Symptoms Abnormal non-rapid eye movement stage IV sleep ** Generalized fatigue or tiredness ** Chronic headache ** Anxiety Irritable bowel syndrome A.M. Stiffness 9 3

5 Signs & Symptoms Depression Reduced physical endurance Decreased social interaction Cognitive fog Subjective, non-confirmable : Paresthesias Swollen joints All sx may wax & wane 10 Most Common Complaints # 1 : Sleep problems # 2 : Fatigue # 3 : Cognitive dysfunction # 4 : Pain Fibromyalgia is much more than a pain disorder 11 What Causes FM? Cause is unknown and is probably multifactorial and may be different in different patients 12 4

6 Some Causes of FM? Lower levels of Serotonin: Related to sleep, pain perception, HAs, & mood disorders Dopamine: Related to pleasure, motivation, & motor control; lower levels in FM patients 2 nd -ary to pain stimulus Growth hormone 2 nd -ary to sleep disruption; related to tissue repair 13 What Causes FM? Abnormally high levels of Substance P in spinal fluid in some patients Substance P important in transmission and amplification of pain signals to and from brain Areas of brain activated with mild tactile pressure: 2 in controls vs. 12 in FM Volume control is turned up too high in brain s pain centers 14 Altered Neuro Structure Chronic pain accompanied by cortical reorganization : Flor, Neurosci Lett, 1997 Chronic back pain is accompanied by brain atrophy : Apkarian, Neurosci,

7 Grey Matter Loss in Fibromyalgia Burgmer M, et al. Psychosom Med. 2009;71: Kuchinad A, et al. J Neurosci. 2007;27: Wood PB, et al. Eur J Neurosci. 2007;25: All images adapted. 16 What Causes FM? Familial tendency to develop FMS suggests genetic role Can be triggered by physical, emotional or environmental stressors such as car accidents, repetitive injuries and certain diseases : Rheumatoid arthritis and SLE pts. are more likely to develop FMS 17 Who Gets FM? Affects as many as 1 in 30 Americans Most common in middle-aged women Men and children also get the disorder More likely with : RA, SLE and Ankylosing spondylitis Other family members with FMS Lower income & education Prevalence increases to age

8 Differential for Fibromyalgia Hypothyroidism Muscle overuse Inflammatory disorders: Myopathies Polymyalgia rheumatica Temporal arteritis Chronic Fatigue R.A. SLE 19 How is FM diagnosed? Symptoms of FM are typically very non-specific, common to many other conditions. Many sx cannot be objectively evaluated. 20 How is FM diagnosed? 2 sets of criteria: 1990 & 2010?research vs. clinical? 1990 considered the Gold standard Can use either one Choose the one better for you & your clinic 21 7

9 2010 Fibromyalgia Criteria Contains 2 scoring subsets Widespread Pain Index (WPI) Symptom Severity Score (SSS) Uses floating combinations of these 2 scores E.G. WPI >7 & SSS>5 or WPI 3-6 & SSS > ACR Diagnostic Criteria for FM and Measurement of Symptom Severity Widespread pain index (WPI) and symptom severity (SS) scale score Symptoms have been present at similar level for > 3 months Patient does not have another disorder that would otherwise explain the pain No physical examination necessary Can be self-administered Probably more sensitive to change than ACR criteria Wolfe F, et al. Arthritis Care Res. 2010;62: How is FM diagnosed? (1990) Diagnosis made by evaluation of symptoms & presence of tender points Not a diagnosis of exclusion Widespread pain for at least 3 months and pain in 11 out of 18 tender point sites on digital palpation 24 8

10 ACR Diagnostic criteria Both criteria must be satisfied History of widespread pain for more than 3 months, on both sides of the body, above and below the waist, and axial skeleton (cervical spine, anterior chest, thoracic pain, or low back) Pain in 11 of 18 tender point sites on digital palpation with approximate force of 4 kg. Presence of second clinical disorder does not exclude diagnosis of fibromyalgia. 25 Fibromyalgia Impact Questionnaire Assesses functional abilities in daily life & Measures patient progress & outcomes Self-administered, 10 item questionnaire 10 Minutes to complete Good Validity 26 ACR diagnostic criteria History of chronic widespread pain 3 months Patients must exhibit 11 of 18 tender points FM can be identified from among other rheumatologic conditions with use of ACR criteria with good sensitivity (88.4%) and specificity (81.1%) ACR Diagnostic Criteria 27 9

11 Physical Exam Requirement Systematic palpation of the 18 tender point sites. Palpation force is 4 kg Equal to the force needed to just blanch your thumbnail 28 How is FM Diagnosed? X-rays, blood tests, specialized scans such as nuclear medicine and CT, muscle biopsies are all normal Objective markers of inflammation such as ESR are normal Distinguish from other common diffuse pain conditions; e.g. RA, SLE, Hypothyroidism and Polymyalgia Rheumatica 29 LABS to Get ESR CBC, TSH, ANA CPK If any abnormality, work it up. Probably not fibromyalgia 30 10

12 How is FM treated? Fibromyalgia is a chronic condition managed with both medications and physical modalities Medication therapy is largely symptomatic, as there is no definitive treatment nor cure for fibromyalgia 31 From Mechanism to Treatment Central neural factors play a critical role Treatments at the periphery (drugs, injections) are not efficacious This is a polygenic disorder There is a deficiency of noradrenergic-serotonergic activity Lack of sleep or exercise increases pain and other somatic sx, even in normals How FM patients think about their pain may directly influence pain levels There will be sub-groups of FM needing different treatments Drugs that raise norepinephrine and serotonin will be efficacious in some Exercise, sleep hygiene, and other behavioral interventions are effective therapies for biological reasons Cognitive therapies are effective in FM 32 Medications in FM Strong evidence : A Rec Amitriptyline, mg at bedtime Cyclobenzaprine, mgs at bedtime Pregabalin, 450 mg/day Gabepentin, mg/day Duloxetine, mg/day Milnacipran, mg/day 33 11

13 Medications in FM Modest evidence : B Rec Tramadol, mg/day SSRIs (fluoxetine, sertraline) Weak evidence: pramipexole, gamma hydroxybutyrate, growth hormone, 5- hydroxytryptamine, tropisetron, s-adenosylmethionine 34 No Evidence: Opioids, NSAIDS, benzodiazepene and nonbenzodiazepene Hypnotics, melatonin, magnesium, DHEA, thyroid hormone, OTCs 35 Only 3 Meds are FDA Approved for FM Duloxetine (Cymbalta) Pregabalin (Lyrica) Milnacipran (Savella) These meds differ in the Sx of FM they relieve 36 12

14 Nonpharmacologic Strategies Strong Evidence : A Rec Exercise : Must be > moderate (> 50% max HR) Physical and psychological benefits 2-3 X per week for 4-6 weeks to see effect Efficacy not maintained if exercise stops Cognitive-behavioral therapy : A Rec Improvements in pain, fatigue, mood, and physical function Improvement often sustained for months Patient education/self-management Improves pain, sleep, fatigue, and quality of life Combination (multidisciplinary therapy) : A Rec 37 Nonpharmacologic Strategies: Strong Evidence: Sleep restoration Modest Evidence Strength training Acupuncture Hypnotherapy EMG biofeedback Balneotherapy Wgt loss Weak Evidence Chiropractic Manual and massage therapy?? Ultrasound Vitamin D Diets No Evidence Tender-point injections Flexibility exercise 38 Outcomes in FM Most patients have chronic, persistent symptoms Most patients continue to work, but 10-15% are disabled Duration of time without a diagnosis adversely affects outcome Subsets of patients important in outcome Mode of onset: (a) Infection (b) Trauma Work setting Medicolegal setting Concurrent medical and psychiatric illness Levels of coping, catastrophizing Primary vs tertiary referral patients 39 13

15 Prognosis With resolution of sleep disturbance, may resolve totally Aggressive physical therapy is critical in those who do not respond Approximately 5% do not respond to any form of therapeutic intervention. Hypnosis may be attempted in that group. 40 Initial Treatment of Fibromyalgia As a first-line approach for patients with moderate to severe pain, trial with evidence-based medications, e.g. Trial with low-dose tricyclic antidepressants, SSRI, SNRI, antiseizure medication Provide additional treatment for comorbid conditions Stress management techniques. Encourage exercise according to fitness level 41 Further Treatment Polypharmacy; for example, trial of SSRI in AM and tricyclic in PM ( A Rec) SNRI in AM and anti-seizure drug in PM Trial of additional analgesics such as tramadol Structured rehabilitation program; Formal mental health program, such as CBT for patients with prominent psychosocial stressors, and/or difficulty coping, and/or difficulty functioning. Comprehensive pain management program 42 14

16 Patients Benefit From: Regular psychosocial support Education about her disease Patient support group Structured exercise program Improved sleep hygiene Supportive family environment Pacing Healthy lifestyles Address smoking, alcohol, sleep Appropriate medication 43 FM and Mood Disorders At the time of FM diagnosis, mood disorders are present in 30-50%, primarily depression. Increased prevalence of mood disorders is primarily in tertiary-referral patients. Increased lifetime and family history of mood disorders in FM vs RA (Odds = 2.0). Fibromyalgia co-aggregates with major mood disorder in families (OR 1.8 [95% CI 1.1, 2.9), p=0.01). 44 Patient Follow-up Routine, regular follow-up Monitor patient s progress Assess: Pain Sleep Daily functioning Global well-being Mood disorders Can use the FIQR (free) 45 15

17 Art of FM Therapy Individualize therapy Exhaustion, mood dominate: start with SNRI Pain, sleep dominate: start with anti-seizure drug TCA in low dose at bedtime (hs) still can be effective For any drug: start low, go slow Amitriptyline: 10 mgs hs Duloxetine: mgs AM with food Pregabalin: 50 mgs hs Gabepentin 100 mg hs Often will not achieve recommended dose because of adverse side effects May be better to add 2nd drug rather than switch but polypharmacy trials not yet published Non-pharamacologic therapy is as important as drugs 46 Most patients require multi-component therapy Principles of Treatment Reduction of Pain: Behavioral, Meds, Blocks, Surgery, Complementary There is no magic bullet, no single cure Rehabilitation: Reconditioning & Prevention Coping: Management of Residual Pain 47 Treatment Objectives (Negotiated) Decrease the frequency and / or severity of the pain General sense of feeling better Increased level of activity Return to work Decreased health care utilization Elimination or reduction in medication usage 48 16

18 Explaining the Typical Outcome FM does not herald a systemic disease No progressive, structural or organ damage Most patients in specialty practice have chronic, persistent symptoms Primary care patients more commonly report complete remission of symptoms Most patients continue to work, but 10-15% are disabled Most patients quality of life improves with medical management 49 Fibromyalgia Conclusions FM is a recognized disorder Pathophysiology not completely elucidated Choosing optimal treatment has recommendations, but may still be a trial-and-error process Duloxetine, Pregabalin & Milnacipran are the only FDAapproved meds Treat the whole patient, including co-morbidities Best non-pharmacologic modalities are Exercise & CBT» 50 Bibliography Wolfe F et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33: Okifuji A et al. A standardized manual tender point survey. 1. Development & determination of a threshold point for the identification of positive tender points in fibromyalgia syndrome. J Rheum 1997;24: Chakrabarty S & Zoorob R. Fibromyalgia. Am Fam Physician 2007;76:

19 Bibliography AMA. Module 1 Pain Management: Pathophysiology of Pain & Pain Assessment. Feb Dworkin RH et al. Recommendations for the pharmacological management of neuropathic pain. Mayo Clin Proc. 2010;85:S3-S13. Moriarty O, et al. The effect of Pain on cognitive function. Prog Neurobiol. 2011;93: Traynor LM, et al. Pharmacotherapy of Fibromyalgia. Am J Health-System Pharmacy. 2011;68: Cochrane Review : For the FIQR, see Medication Use Agreement : 52 Bibliography Cochrane Database : Rooks DS. Fibromyalgia Treatment Update. Curr opin Rheumatol. 2007;19: Carville SF et al. EULAR evidence based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67: Buckner WJ. Fibromyalgia. Medscape reference. Feb Maizesl M & McCarberg B. Antidepressants & Antiepileptic Drugs for Chronic Non-cancer Pain. AFP 2005;71: You made it through another presentation!! 54 18

20 Extra Slides 55 You may have heard something about using antipsychotics in fibromyalgia Quetiapine mg/day Ziprasidone 20 mg/day Each has 1 study done Both used as add-on to inadequate other therapy Both showed some parameter improvement, but Both have significant side effects 56 What about a dopamine agonist? Pramipexole, in 1 study, did show significant improvement in several parameters, but Again : Significant side effects 57 19

21 Who Should Treat Fibromyalgia? More than 50% of visits are to primary care physicians Currently, 16% of FM visits are to rheumatologists The American College of Rheumatology suggest that rheumatologists serve as consultants (tertiary care) Other specialists should include mental health professionals, physiatrists and pain management experts 58 What about Diet for Fibromyalgia? No magic diet No controlled studies, but May suggest avoidance of foods associated with fatigue : High fat Junk food Refined sugar Caffeine White flour Salt Fried foods Alcohol 59 The Fibromyalgia Headache In the category of the Chronic Daily Headache More resembles a tension-type HA Involves neck muscles leading to pressure on occipital nerve 60 20

22 Tricylics in Fibromyalgia AMITRIPTYLINE Four placebo-controlled trials Goldenberg,1985 Carette,1986 Carette,1994 Dose mg Duration 6-26 weeks All showed modest efficacy CYCLOBENZAPRINE Four placebo-controlled trials Quimby, 1989 Carette, 1994 Reynolds,1991 Dose mg Duration 4 12 weeks 2 showed efficacy 61 Milnacipran Number 1196 PL controlled, double blind, Randomized Pain composite VAS - 30% + very much or much impr on PGIC FM composite pain composite + 6 pt impr on PCS of SF36 Secondary PGIC, SF36 (PCS and MCS) and FIQ total Baseline observation carried forward (BOCF) at 3 mnths 39,46% achieved Pain composite, v 25% PL (0.011, 0.015) 25,26% achieved FM composite, v 13% PL (0.025, 0.004) Generally well tolerated (discontinuations 34,35% v 28% PL) Common AEs nausea M 37%, PL -20% (both studies) headache M 18%, PL -14% constipation M 16%, PL -4% hyperhidrosis M 9%, PL - 2% NB no sig hypertension or wt gain 62 21