New Developments in Diagnosis and Management of Fibromyalgia

Transcription

1 New Developments in Diagnosis and Management of Fibromyalgia Boston, Massachusetts November 12, 29

2 Session 3: New Developments in Diagnosis and Management of Fibromyalgia Learning Objectives 1. Identify the differential diagnosis of chronic musculoskeletal pain and three clinical characteristics that suggest a diagnosis of fibromyalgia. 2. Outline evidence based treatment strategies for fibromyalgia, including two nonpharmacologic and two pharmacologic strategies for utilization in your practice. Faculty Rakesh Jain, MD, MPH Director, Psychiatric Drug Research R/D Clinical Research Center Lake Jackson, Texas Rakesh Jain, MD, MPH, is director of psychiatric drug research for the R/D Clinical Research Center at Lake Jackson, Texas. Dr Jain attended medical school at the University of Calcutta in India. He then attended graduate school at the University of Texas School of Public Health in Houston, where he was awarded a National Institute/Center for Disease Control Competitive Traineeship. His research thesis focused on alcohol abuse issues. He graduated from the School of Public Health in 1987 with a Masters of Public Health (MPH) degree. After graduate school, Dr Jain completed a postdoctoral fellowship in Research Psychiatry with the Gerontology Center of the University of Texas Mental Sciences Institute in Houston. He received the National Research Service Award for the support of the postdoctoral fellowship. After this, he served a 3-year residency in psychiatry at the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical School at Houston as well as a 2-year fellowship in Child and Adolescent Psychiatry. Dr Jain is currently involved in multiple research projects studying the effects of medications on short- and long-term treatment of depression, anxiety, pain/mood overlap disorders, and psychosis in adult, child, and adolescent populations. He is the author of several articles on the issue of mood and pain conditions. He serves on several Boards focusing on drug development and disease state education. He was recently named Public Citizen of the Year by the National Association of Social Workers, Gulf Coast Chapter, in recognition of community and peer education and championing of mental health issues. He was also recently awarded the Extra Mile Award by the local school district, in recognition of the service to the children of the school district and consultation to the teachers and counselors Kevin S. Ferentz, MD Associate Professor Department of Family Medicine University of Maryland School of Medicine Baltimore, Maryland Dr Kevin Ferentz is associate professor, Department of Family Medicine, University of Maryland School of Medicine, Baltimore, where he has also been residency director since He is a Diplomate of the National Board of Medical Examiners, Diplomate of the American Board of Family Practice, and a Certified Medical Reviewer Officer of the American Association of Medical Review Officers. Dr Ferentz has authored more than 2 dozen articles and book chapters on various issues in family medicine. He is the recipient of the Exemplary Teaching Award from the American Academy of Family Physicians. Ladies Home Journal named him one of the Best Family Physicians in America in 22. He is considered a national thought leader on the care of mental illness in the primary care setting. For 8 years he was the regular host of Sunday Rounds, the largest medical call-in show on public radio, heard nationwide and around the world on the Armed Forces Radio Network and the Internet. Dr Ferentz is a past president of the Maryland Academy of Family Physicians and a member of the American Academy of Family Physicians, Society of Teachers of Family Medicine, and Association of Family Practice Residency Directors. He serves on the editorial boards of Medicine and Behavior and The Primary Care Companion to the Journal of Clinical Psychiatry. In addition, Dr Ferentz serves as reviewer for American Family Physician, Managed Care, and Family Medicine. Dr Ferentz received his MD degree from the State University of New York at Buffalo School of Medicine. After completing his family practice residency at the University of Maryland, he completed a fellowship in faculty development with an emphasis in obstetrics Session 3

3 Faculty Financial Disclosure Statements The presenting faculty reported the following: Dr Jain is a consultant for, receives research support from, and is on the speakers bureau of Eli Lilly and Company, Pfizer Inc, and Forest Pharmaceuticals, Inc. Dr Ferentz has nothing to disclose. Education Partner Financial Disclosure Statement: The content collaborators at Turnkey Solutions, LLC have reported the following: Emily A. Bakerman, RN, MS, APN-C, executive vice president, has nothing to disclose. Drug List Generic Trade Generic Trade amitriptyline Elavil nortriptyline Pamelor cyclobenzaprine Flexeril pregabalin Lyrica desipramine Norpramin, Pertofrane tramadol Ultracet, Ultram duloxetine Cymbalta venlafaxine Effexor gabapentin Neurontin guaifenesin Mucinex Investigational hydrocodone + acetaminophen Anexsia, Co-Gesic, Lortab, Vicodin tropisetron Navoban imipramine Tofranil Off-Label milnacipran Savella (outside US: Ixel, (Midalcipran) cyclobenzaprine, gabapentin, tramadol, venlafaxine Suggested Reading List Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics. 2;41(2): Arnold LM, Rosen A, Pritichett YL, et al. A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder. Pain. 25;119:5-15. Arnold LM. Biology and therapy of fibromyalgia. New therapies in fibromyalgia. Arthritis Res Ther. 26;8:212. Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 26;67(8): Borsook D, Moulton EA, Schmidt KF, Becerra LR. Neuroimaging revolutionizes therapeutic approaches to chronic pain. Mol Pain. 27;3:25. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev. 22;(3):CD3786. Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 25;52(4): Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 22;46(5): Jain AK, Carruthers BM, van de Sande MI. Fibromyalgia Syndrome: Canadian Clinical Working Case Definition, Diagnostic and Treatment Protocols A Consensus Document. J Musculoskeletal Pain. 23;11(4):3-17. Kuchinad A. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 27;27: Loevinger BL, Muller D, Alonso C, Coe CL. Metabolic syndrome in women with chronic pain. Metabolism. 27;56(1): Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 26;27(1): Rooks DS, Gautam S, Romeling M, et al. Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial. Arch Intern Med. 27;167(2): Thieme K, Turk DC, Flor H. Responder criteria for operant and cognitive behavioral treatment of fibromyalgia syndrome. Arthritis Rheum. 27;57(5) Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 199 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 199;33(2): Session 3

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5 New Developments in Diagnosis and Management of Fibromyalgia RAKESH JAIN, MD, MPH Director, Psychiatric Drug Research R/D Clinical Research Center Lake Jackson, Texas Fibromyalgia (FM): Tough Questions Worth Asking Is it physical or psychological? Can it be reliably diagnosed? Is a diagnosis helpful or harmful? Are any treatments effective? First Things First Pain is a Common Issue in Both Sexes & All Age Groups Prevalence of Chronic Painful Physical Conditions (CPPCs) by Age Group and Gender Prevalence of CPPC Men (N=9,116) Women (N=9,864) Age Group (Years) P<.1 between age groups (15-24-year-old and year-old groups vs year-old and >65-year-old groups) and between genders Ohayon MM. J Clin Psychiatry. 24;65(Suppl)12:5-9. Fibromyalgia: An Introduction Fibromyalgia : common, chronic pain disorder characterized by widespread pain and somatic symptoms 1 Prevalence in industrialized countries, ~2%-4% 2 Most common rheumatologic disorder after osteoarthritis More common in women (as with most pain disorders) than men Prevalent in all ethnic groups 1 Arnold LM, et.al. J Clin Psychiatry. 29;69(12)e35. 2 Wolfe F, et al. Arthritis Rheum. 1995;38(1): Occiput Trapezius Supraspinatus Gluteal Greater trochanter Assessing for Fibromyalgia The American College of Rheumatology Criteria for the Classification of Fibromyalgia Low cervical Second rib Lateral epicondyle Knee History of widespread pain has been present for at least 3 months Pain is considered widespread when all of the following are present: Pain in both sides of the body Pain above and below the waist Pain in 11 of 18 tender point sites on digital palpation Wolfe F, et al. Arthritis and Rheum. 199;33(2): Overlap Between Fibromyalgia and Related Disorders Fibromyalgia 2-4% of population Defined by widespread pain and tenderness Has frequent cognitive dysfunction Regional Pain Syndromes IBS Painful bladder/interstitial cystitis [PBS/IC] TMD Tension Headache Vulvodynia IBS = Irritable bowel syndrome PTSD = post-traumatic stress disorder TMD = temporomandibular disorders Pain and/or sensory amplification Chronic Fatigue Syndrome (CFS) 1% of population Fatigue and 4 of 8 minor criteria Psychiatric Disorders Major depression OCD Bipolar PTSD General Anxiety Disorder Panic attack Somatoform Disorders 4% of population multiple unexplained symptoms no organic findings Clauw DJ, Chrousos GP. Neuroimmunomodulation. 1997;4(3):

6 Fibromyalgia: Associated Symptoms Other Somatic Symptoms and Comorbidities Three cardinal symptoms of FM (besides Pain) 1 : Fatigue Non-refreshing sleep Fibrofog (difficulty concentrating) Comorbid conditions Localized pain syndromes (noncardiac chest pain, headache) Irritable bowel syndrome 2 Temporomandibular disorder Chronic fatigue syndrome 2 1 Clauw DJ. J Clin Psychiatry (11):e33. 2 Buskila D, Cohen H. Curr Pain Headache Rep. 27;11(5): Differentiating FM from Osteoarthritis FM Wide spread pain Muscles, ligaments primarily affected Typically female in the age range Non-anatomic distribution of pain No specific radiological findings Osteoarthritis Typically more localized Joints primarily affected Typically an older patient of either sex Pain typically in joint affected Radiological findings typically found Bliddal H. et al. Best Pract Res Clin Rheumatol. 27.;21(3): Lawrence RC et al. Arthritis Rhuem. 27;58(1):26-35 Risk Ratio of Various Comorbidities Psychiatric) With Fibromyalgia (Psychiatric and Non-Psychiatric) Risk Ratio Male Female (Compared to Those Without Fibromyalgia) Depression Anxiety IBS RA Headache FM and Mood Disorders At the time of FM diagnosis, mood disorders are present in 3-5%, primarily depression and anxiety Increased prevalence of mood disorders are primarily in tertiary-referral patients Increased lifetime and family history of mood disorders in FM vs RA (Odds = 1.8) FM aggregates in families and co-aggregates with mood disorders. Odds of having FM in relatives is 8.5 in FM vs RA proband RA = rheumatoid arthritis Weir PT, et al. J Clin Rheumatol. 26;12(3): Arnold LM, et al. Arthritis Rheum. 24;5(3): Disability with Depression, FM, and Depression plus FM A Primary Care Clinician s Diagnostic Paradigm for FM % of Patients % of Time MDD FM MDD + FM Suspect fibromyalgia in all patients reporting significant pain/fatigue symptoms Conduct the ACR examination on all such patients (takes only minutes, and it is approximately 85% sensitive and specific for FM) Carefully screen for comorbidities: consider mood disorder, anxiety disorders, eating disorders, substance use disorders, etc. Create an individualized treatment plan. Permanent Disability Restriction of Activity MDD = major depressive disorder Kassam A, Patten SB. BMC Musculoskelet Disord. 26;7:4. ACR = American College of Rheumatology Goldenberg DL, et al. JAMA. 24;292(19):

7 Genetics of Fibromyalgia Neurobiology of Fibromyalgia Familial predisposition 1 Most recent work by Arnold, et al, suggests >8 odds ratio (OR) for first-degree relatives, and much less familial aggregation (OR 2) with major mood disorders Much stronger with bipolarity, obsessive compulsive disorder Genes that may be involved 5-HT2A receptor polymorphism T/T phenotype 2 Serotonin transporter 3 Dopamine D4 receptor exon III repeat polymorphism 4 COMT (catecholamine O-methyl transferase) 5 1. Arnold LM, et al. Arthritis Rheum. 24;5(3): Bondy B, et al. Neurobiol Dis. 1999;6(5): Offenbaecher M, et al.. Arthritis Rheum. 1999;42(11): Buskila D, et al. Mol Psychiatry. 24;9(8): Gürsoy S, et al. Rheumatol Int. 23;23(3): Substance P Supraspinal Influences on Pain and Sensory Processing Facilitation Glutamate/EAA Serotonin (5HT 2a, 3a ) Nerve growth factor Cholecystokinin (CCK) + Inhibition Descending antinociceptive pathways Norepinephrineserotonin (5HT 1a,b ), dopamine Opioids GABA Cannabinoids Adenosine GABA = gamma-aminobutyric acid Millan MJ, Progress in Neurobiology. 22;66(6): Scholz J, Woolf CJ. Nature Neuroscience. 22;5: fmri of Central Sensitization in FM 16 FM patients vs. 16 healthy controls Pain intensity fmri = functional magnetic resonance imaging fmri Studies Show Cortical/Subcortical Augmentation of Pain Processing in FM Fibromyalgia 4 Subjective pain control Stimulus pressure control Stimulus intensity (kg/cm 2 ) Gracely RH, et al. Arthritis Rheum. 22;46(5): Fibromyalgia (FM): Treatment Options Nonpharmacologic Exercise CBT OBT Acupuncture Chiropractic manipulation Psycho-education CBT = cognitive behavioral therapy OBT = operant behavioral therapy Pharmacologic FDA Approved: Pregabalin Duloxetine Milnacipran Not FDA Approved: TCAs Cyclobenzaprine Tramadol Nonpharmacologic Treatment Options in Fibromyalgia Jain AK, et al. J Musculoskeletal Pain. 23;11(4):3-17; 3

8 Exercise in Fibromyalgia: A Meta-Analysis of Studies Worsening % Aerobic Performance Tender Point Pain Pressure Threshold -7. Improvement in Pain -1.6 Control Group.5 Improvement % Exercise Intervention Group Busch AJ, et al. Cochrane Database Syst Rev. 22;(3):CD3786. Key Elements of Cognitive Behavioral Therapy for Fibromyalgia Psycho-Education Realistic goal setting Relaxation training Behavioral pacing Identifying dysfunctional thought patterns Communication skills training Relapse prevention Bennett R, Nelson D. Nat Clin Pract Rheumatol. 26;2(8): Long-Term Benefits of Psychotherapy in Fibromyalgia (12-Month Follow-Up Data) Cognitive Behavioral Therapy Operant Behavioral Therapy N= 125 CBT n=42 OBT n=43 AP n=4 Attention Placebo (% of patients reporting) FIQ score Multi-Modal Modal Interventions in FM Benefits of exercise enhanced by self-management education AE ST FSHC ST-FSHC Intervention Group Fibromyalgia Impact Questionnaire (FIQ) scores at baseline, postintervention assessment (PIA), and 6-month follow-up (PIA6) in the 4 intervention groups. P<.5 and P<.1 at 6 months vs baseline Baseline PIA PIA6 Clinically significant reduction of pain Clinically significant increase of pain Thieme K, et al. Arthritis Rheum. 27;57(5): AE=aerobic and flexibility exercise FSHC=Fibromyalgia Self-Help Course ST=strength training, aerobic, and flexibility exercise ST-FSHC=a combination of ST and FSHC Rooks DS, et al. Arch Intern Med. 27;167(2): TCAs in Fibromyalgia: Wide Spectrum of Action Pharmacologic Treatment Options in Fibromyalgia Effect Size (Standard Deviations) Patient Global Assessmen t M.D. Global Assessmen t Pain Fatigue Sleep Tenderness Stiffness Outcome Measure Note no TCAs are FDA approved for FM Arnold LM, Keck PE, Welge JA, et al. Psychosomatics. 2;41:

9 Fibromyalgia FDA Approved Treatment Pregabalin Least Squares Mean Pain Score P <.5; P <.1 vs placebo Base- Line Placebo Pregabalin 15 mg/day Pregabalin 3 mg/day Pregabalin 45 mg/day End- Point Week Crofford LJ, et al. Arthritis Rheum. 25; 52(4): // Survival distribution function 1% 75% 5% 25% Pregabalin Longer Term Duration of Effect Primary event time (DB days) Kaplan-Meier plot of time to loss (in days) of therapeutic response Comparison of pregabalin with PBO in time to LTR (log-rank test): P<.1 Pregabalin arm Placebo arm LTR by end of DB Placebo: 174 patients (61%) Pregabalin: 9 patients (32%) Crofford LJ, et al. Pain 28;136: Fibromyalgia FDA Approved Treatment Duloxetine LS Mean Change from Baseline BPI Average Pain Severity Improvement Weeks Placebo Duloxetine 6 mg QD -1 Duloxetine 6 mg BID P< P.1 vs placebo Phase III Study: Female Patients (N=354); BPI = brief pain inventory. LS = least squares Arnold LM, et al. Pain.25;119(1-3):5-15. Improvement Least-squares Mean Change BPI Average Pain Score Phase III Study: Male and Female Patients (N=52) MMRM Placebo Duloxetine 6 mg QD Duloxetine 6 mg BID LOCF Weeks Endpoint P.5 P.1 P.1 vs placebo MMRM = Mixed Model Repeat Measures Russell IJ et al. Musculoske Pain. 28;136: Mean Change Duloxetine in FM Patients With and Without Comorbid Major Depression No Current MDD P<.1 vs. Placebo P<.1 vs. Placebo BPI Average Pain Current MDD Subgroup P-value =.83 Therapy by subgroup P-value =.323 Mean Change No Current MDD FIQ Average Pain Duloxetine Placebo Current MDD Subgroup p-value =.997 Therapy by subgroup P-value =.348 Arnold LM, et al. J Women s Health. 27;16(8): Fibromyalgia FDA Approved Treatment Milnacipran Pain Intensity (%) Baseline ITT Diary Weekly Pain (LOCF) 7 MIL bid 7 MIL bid 6 MIL qd 6 MIL qd PBO PBO Dose Titration P =.25 bid vs PBO Treatment at MTD Weeks Baseline ITT Diary Daily Pain (LOCF) Dose Titration P =.191 bid vs PBO Treatment at MTD Gendreau RM, et al. J Rheumatol 25;32(1): Vitton O, et al. Hum Psychopharmacol 24;19(suppl 1):S27-S35. 5

10 Milnacipran in FM: Early and Sustained Improvement in Pain through 6 Months (OC) Placebo (n=128) -6 Milnacipran 5 mg BID (n=115) -8 Milnacipran 1 mg BID (n=24) Week mg/d 2 mg/d P <.5 P.1 P.1 LS Mean Change from Baseline (VAS) Percentage of Patients 1% 9% 8% 7% 6% 5% 4% Gabapentin in Fibromyalgia 3% 2% 1% % Gabapentin (N=75) Placebo (N=75) Worse No Change Better P<.1 for difference between groups Participant ratings of global improvement at week 12 (last observation carried forward) in the gabapentin and placebo groups. Data set shown is observed cases (OC). Negative score denotes improvement. Mease PJ, et al. J Rheum. 29;36(2): Note Gabapentin is not FDA approved for FM Dose range = 12 to 24 mg / day Median dose at end point was 18 mg per day Arnold LM, et al. Arthritis & Rheum (4): Cyclobenzaprine in Fibromyalgia Bennett (1988) Carette (1994) Quimby (1989) Note Cyclobenzaprine is NOT FDA approved for FM (meta-analysis analysis of three studies) Favors Placebo Favors Treatment Overall (95 % CI) 3. (95% CI: ) 1 25 Individual study & summary effect size on dichotomous outcomes of improvement Tofferi JK et al. Arthritis Rhum.24;51(1):9-13. Bennett RM et al. Arthritis Rheum. 1988;31: Carette S. Arthritis Rheum.1994;37:32-4. Quimby LG et al. J Rheumatology. 1989;16 suppl 19: Worse Health Change in Mean FIQ Score from Baseline Better Health Tramadol In Fibromyalgia Physical Function Day of Work Missed Interference with Ability to Do Job Note Tramadol is not FDA approved for FM Pain Severity Tiredness Placebo Tramadol / APAP n = 157 n = 156 Interference with Rest Stiffness Anxiety P <.5 Depression Improvement in health-related quality of life after up to 91 days of double-blind treatment with tramadol/acetaminophen or placebo. A, Change in mean standardized Short Form 36 Health Survey score from baseline. B, Change in mean Fibromyalgia Impact Questionnaire (FIQ) score from baseline. P<.5 versus placebo. APAP = acetaminophen. Bennett RM, et al. Arthritis & Rheum. 25;53(4): COMMON SIDE EFFECTS OF Medications used in FM Pregabalin, Gabapentin dizziness, somnolence, dry mouth, blurred vision,weight gain, concentration and memory difficulties SNRIs (duloxetine, venlafaxine, milnacipran) nausea, dry mouth, constipation, somnolence, hyperhidrosis, decreased appetite TCAs (amitypytyline, imipramine, desipramine, nortriptyline) sedation, weight gain, dry mouth, blurred vision, constipation Cyclobenzaprine drowsiness, dry mouth, fatigue, headache Tramadol nausea, constipation,dizziness, somnolence Treatment Guidelines: Focus on APS Guidelines & EULAR Guidelines Source: Package Inserts of medications. Accessed February 28, 29 at 6

11 American Pain Society (APS) Guidelines Step 1 Step 2 Step 3 1. Confirm the diagnosis 2. Explain the condition to patient 3. Evaluate, treat comorbidities (mood, sleep) 1. Trial with low dose TCAs or cyclobenzaprine 2. Begin cardiovascular fitness program 3. Cognitive-behavioral therapy 1. Refer to a specialist if needed (Rheum, Psych, Pain Mgmt) 2. Trial with SSRI or SNRI or tramadol 3. Medication combination or an anticonvulsant European Union League Against Rheumatism (EULAR) Guidelines - Comprehensive assessment - Appreciate FM is a d/o of abnormal pain processing - Multidisciplinary approach for pain, depression, fatigue, sleep disturbances - Heated pool treatment - Exercise - Aerobic and strength training Cognitive-behavioral therapy - Relaxation, rehabilitation, physiotherapy, psychological support - Tramadol, acetaminophen, weak opiates 8. - Antidepressants 9. - Other medication options Goldenberg DL, et al. JAMA. 24;292(19): Carville SF, et.al. Ann Rheum Dis. 28 Apr;67(4): Epub 27 Jul 2 (online : In Conclusion 4 Crucial Points FM is commonly encountered in PCP settings It is frequently comorbid (with both nonpsychiatric & psychiatric comorbidities) Robust neurobiologic data points to a central pain processing etiology of FM It is an impairing disorder: there are now several well referenced studies of available nonpharmacologic and pharmacologic treatment Case Presentation KEVIN S FERENTZ, MD Associate Professor Department of Family Medicine University of Maryland School of Medicine Baltimore, Maryland Case 1: 39-year-old female Widespread muscle pain for 1 years. I ache like a 1-year- old woman. It s ridiculous. Poor sleep (both initial and middle insomnia) Bouts of anxiety and depression never treated Years of vague abdominal pain with alternating constipation and diarrhea Pelvic pain and bladder irritability Evaluation Past Medical History Chronic headaches since age 9 Treated as migraine and tension headaches Social History Married; no children Accountant No history of sexual abuse Physical exam: normal Labs ANA, ESR, RF, CBC: normal X-rays of knees, back, hands: normal 7

12 TEST YOUR KNOWLEDGE Which of the following would be most helpful in distinguishing other rheumatologic disorders from fibromyalgia? 1. Fatigue and trouble sleeping 2. Tenderness only over the joints 3. Meets DSM-IV diagnostic criteria for major depression 4. Sleep disturbance 5. Normal x-rays? Distinguishing Fibromyalgia from Other Rheumatologic Disorders Nonspecific somatic symptoms, particularly fatigue and sleep complaints, are common in multiple rheumatologic and pain conditions Depressive and anxiety disorders are also prevalent in many rheumatologic conditions Laboratory tests (ESR or x-ray findings) are generally discriminatory only if they are abnormal The tender points seen with fibromyalgia are not limited to the joints but are on right and left sides of body, upper and lower, proximal and axial. More Practical Information on Fibromyalgia for Clinicians PHQ-9: A Useful Tool for Screening for MDD in Primary Care 3 cardinal symptoms associated with FM Fatigue Not made better by rest or exercise Memory difficulties Difficulty with memory and concentration Insomnia and sleep disturbances Copies of PHQ-9 freely available on the internet : CREATING A TREATMENT PLAN Based on your assessment, patient is Dx with FM. Depression and anxiety disorders are ruled out. All of these can be considered important in creating her treatment plan, except: 1. Psychotherapy (focus on cognitive therapy) 2. Exercise routine (including aerobic and weight lifting) 3. Disease state education 4. Recommendation to take long-term disability leave 5. Recommendation to involve family in treatment planning? Change From Baseline Fibromyalgia: Long-Term Benefits of Disease Education and Exercise 6-week intervention, end of 6-month follow-up data Control group (n=8) Treatment group (n=84) Pain Relief Depression Anxiety Increases Ability To Do Activities Mean Values: Patient Satisfaction Questionnaire P=.1; P=.65; P=.265; P=.17 Cedraschi C, et al. Ann Rheum Dis. 24;63(3):

13 Nonpharmacologic Therapies Strong Modest Education Aerobic exercise Cognitive behavioral therapy Strength training Acupuncture Hypnotherapy, biofeedback, balneotherapy Strong Modest Pharmacologic Therapies Dual reuptake inhibitors such as Tricyclic compounds (amitriptyline, cyclobenzaprine) Anticonvulsants (pregabalin) Tramadol SNRIs and NSRIs (milnacipran, duloxetine, venlafaxine) Selective serotonin reuptake inhibitors (SSRIs) Gamma hydroxybutyrate Dopamine agonists Weak Chiropractic, manual and massage therapy, electrotherapy, ultrasound Weak Growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine (SAMe) No Tender (trigger) point injections, flexibility exercise No Opioids, corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, guanifenesin Goldenberg DL, et al. JAMA. 24;292(19): Not FDA approved Modified from Goldenberg DL, et al. JAMA. 24;292(19): Case 2: 52-year year-old male Presents with chronic widespread pain, headache,. sleep, and mood + anxiety disturbances Has been out of work for 5 years Past Medical History - Chronic back pain x 2 yrs - Back surgery 5 years previous - Multiple courses of physical therapy and injections for pain, which has helped with back pain Physical Exam: Normal, except widespread tenderness, has 14 out of 18 positive tender points dx of FM made Laboratory findings: Within Normal Limits MRI of back: mild degenerative disc disease, no cord or spinal nerve compression Fibromyalgia: Overlap with Depression and Anxiety Disorders co-occurance odds ratio 7. Major Depression 6. Anxiety Disorder P= No Fibromyalgia controls n = P< Fibromyalgia n =18 Arnold LM, et al. J Clin Psychiatry. 26;67(8): TEST YOUR KNOWLEDGE Patient wants to know why his body hurts, and why he is gaining weight. Which of the following is incorrect information to give to the patients? 1. FM is thought to be as a result of central pain processing abnormalities that is, the brain and spinal cord over perceives pain 2. Pain is the result of overuse of his muscles and joints. Prolonged bed rest until pain goes away is the appropriate approach to helping him 3. His weight gain may be because of complex interactions between brain and body when FM is present? Neuro-endocrine endocrine and Neuro-immune Dysregulation in Pain Syndromes = stimulatory pathway = inhibitory pathway 1 Raison CL, et al. Trends Immunol. 26;27(1): Nestler EJ, et al. Neuron. 22;34(1): Blackburn-Munro G, Blackburn-Munro RE. J Neuroendocrinol. 21;13(12):

14 Neuroendocrine & Autonomic Dysregulation in FM May Lead to Metabolic Syndrome Percentage HC FM HDL = high density lipoprotein Met Syn = metabolic syndrome TG = triglycerides Comparison of 19 FM Patients and 46 HC P<.5 A1C Waist High BP TG HDL Met Syn Metabolic Syndrome Components Loevinger BL, et al. Metabol Clin Experim. 27;56(1): TEST YOUR KNOWLEDGE The patient asks for medication recommendations for his FM symptoms. Which of the following is the LEAST appropriate as first-line therapy? 1. Hydrocodone 2. Pregabalin 3. Duloxetine 4. Milnacipran 5. Tramadol 6. Cyclobenzaprine? Step Approach to a Patient With Fibromyalgia Step 1: Confirm Diagnosis Identify important symptom domains and their severity (pain, sleep disturbance, fatigue) and level of function Evaluate for comorbid medical and psychiatric disorders (sleep apnea, osteoarthritis, depressive or anxiety disorders); may require referral to specialist Assess psychosocial stressors, level of fitness, barriers to treatment Provide education about fibromyalgia (individual or group) Review treatment options Arnold LM. Arthritis Res Ther. 26;8(4):212. Arnold LM. Arthritis Res Ther. 26;8(4):212. Step 2: Create an Individualized Treatment Plan Recommend treatment based on the results of the individual evaluation For patients with moderate-to-severe pain, trial with medication as a first-line approach With or without lifetime depression or anxiety: trial of selective serotonin and norepinephrine reuptake inhibitor (not recommended as monotherapy for patients with comorbid bipolar disorder) Prominent sleep disturbance or anxiety: trial of α 2 Δ ligand Partial response to monotherapy with either selective serotonin and norepinephrine reuptake inhibitor or α 2 Δ ligand: trial of combination of these agents Arnold LM. Arthritis Res Ther. 26;8(4):212. Step 2: (cont) Create an Individualized Treatment Plan Consider other medications if no response to the above approach (selective serotonin reuptake inhibitor [SSRI]; tricyclic antidepressant; combination of SSRI with low-dose TCA [watch for drug interaction between SSRI and TCA]; combination of SSRI and α 2 Δ ligand) Avoid drugs with high likelihood of abuse or dependence Provide any additional treatment for comorbid conditions (nonsteroidal anti-inflammatory drugs for osteoarthritis, continuous positive airway pressure for sleep apnea) Arnold LM. Arthritis Res Ther. 26;8(4):212. 1

15 Step 3: Consider Adjunctive Therapies Helpful Internet Sites to Refer FM Patients Adjunctive CBT for patients with prominent psychosocial stressors, or difficulty coping or functioning Exercise prescribed according to fitness level (goal of 3-6 minutes of low-to-moderate intensity aerobic exercise [walking, pool exercises, stationary bike] at least 2-3 times a week) Encourage participation in supervised or group exercise Arnold LM. Arthritis Res Ther. 26;8(4):212. National Fibromyalgia Association National Fibromyalgia Research Association Obtaining Patient Educational Booklets National Institute of Health (NIH) has an excellent patient informational booklet for patients If patients do not have Internet access, they can call this phone number to order the booklet (877) -22-NIAMS Clinicians can order, for no charge, multiple copies for distribution to patients Take Home Messages FM is in our practices, but frequently under-diagnosed It appears to be a real disorder, with strong comorbidity overlap We PCPs are extremely important in identifying and treating this condition. Early recognition is important. Individualized treatment planning is necessary. Accessed Feb 21,