2. Disclosure This program was developed from an educational grant from Pfizer to the University of Calgary and Université de Sherbrooke. Faculty disclosure

3. Core Development Committee Dr. Christian Cloutier, Neurosurgeon, Quebec Dr. Mary-Ann Fitzcharles, Rheumatologist, Quebec Dr. Algis Jovaisas, Rheumatologist, Ontario Ms. Christal Lacombe, Pharmacist, Alberta Dr. Rhonda Shuckett, Rheumatologist, British Columbia Dr. Richard Ward, Family Physician, Alberta

4. National Committee Dr. Brian Craig, Family Physician, New Brunswick Dr. Alan Kaplan, Family Physician, Ontario Dr. Bernard Martineau, Family Physician, Quebec Dr. Kenneth Stakiw, Family Physician, Saskatchewan Mr. Robert Thiffault, Pharmacist, Quebec

5. Overall Learning Objectives Following this program, participants will Describe the diagnosis and core symptoms of fibromyalgia (FM) Have an approach to explaining the diagnosis of FM to patients Prescribe appropriate pharmacologic and non-pharmacologic interventions based on predominant symptoms

6. Menu (all related to FM) Click on the name of the module you want to access Management of Pain Management of Pain Fatigue Sleep Disturbance Sleep Disturbance Non-pharmacologic Interventions 1 2 3 7 Depression 4 Making the Diagnosis Making the Diagnosis 5 “Selling” the Diagnosis “Selling” the Diagnosis 6 Choice of Medical Therapy Choice of Medical Therapy 8 Incomplete Treatment Response Incomplete Treatment Response 9

8. Objectives Following this module, participants will be able to: Explain the basis of increased pain in patients with fibromyalgia (FM) Discuss the relationship between pain, fatigue and sleep disturbance in FM Suggest non-pharmacologic therapies for pain Prescribe medications that improve pain in FM Recognize the role of an interdisciplinary team in FM management

9. Chronic, widespread pain is the defining feature of fibromyalgia Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance Patients describe it as physically or emotionally draining Fatigue Core Clinical Features of FM Stiffness Stiffness in the morning is a common characteristic of FM Characterized by confusion, slowed processing of information and reaction time, difficulty in word retrieval or speaking, concentration, attention, short-term memory consolidation, disorientation Neurocognitive Impairment (“Fibro Fog”) ACR Fibromyalgia Diagnostic Criteria. 2010. http://www.nfra.net/Diagnost.htm; Carruthers et al. J Chron Fat Synd. 2003;11:7-115; Harding. Am J Med Sci. 1998;315:367-37; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Roizenblatt et al. Arthritis Rheum. 2001;44:222-2306; Wolfe et al. Arthritis Rheum. 1995;38:19-28.http://www.nfra.net/Diagnost.htm Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain

10. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. Patty was advised to attend a local yoga studio, which has a special FM class. She was given a morning medication that targeted mood. As well, she was referred to a local FM support group.

11. Video 1

12. Questions 1.Why do patients with FM have pain? 2.What non-medication approach would you take with Patty? 3.What medical FM therapies improve pain? 4.How could an interdisciplinary team (your own team or resources in your community) assist in the management of patients with FM? Take the time to answer each of the questions

13. Symptoms of FM Pain, fatigue and sleep disturbance are present in at least 86% of patients* 0 20 40 60 80 100 100% 96% 86% 72% 60% 56% 52% 46% 42% 41% 32% 20% Muscular pain FatigueInsomniaJoint pains Head- aches Restless legs Numbness and tingling Impaired memory Leg cramps Impaired Concen- tration Nervous- ness Major depression *United States data ACR 1990 Fibromyalgia Diagnostic Criteria. National Fibromyalgia Research Association Web Site http://www.nfra.net/Diagnost.htm.http://www.nfra.net/Diagnost.htm

14. Pathophysiological Observations in FM Despite extensive research, the exact cause of pain in FM is not clearly understood Peripheral Peripheral sensitization Temporal summation (windup) (short-term) Spine and brain Central sensitization (long-term) Change in grey matter volume Descending inhibition Other factors Hypothalamic-pituitary-adrenal axis dysregulation Sleep disturbance Cognitive effects Staud et al. Nat Clin Pract Rheumatol. 2006;2:90-98; Henriksson. J Rehabil Med. 2003;41(suppl 41):89-94; Crofford et al. Arthritis Rheum. 2002;46:1136-1138; Vaerøy et al. Pain. 1988;32:21-26; Staud. Arthritis Res.Ther. 2006;8:208.

15. Key Messages for Pain Principles in FM There is no “cure” for the pain Active patient involvement: activity and non-medication approaches Important to manage patient’s expectations Normalize sleep Normalize mood Start with medical interventions for pain that have evidence for efficacy in FM Start low, go slow! Target pain control that allows functionality

16. Non-pharmacologic Treatments Patient education Conflicting evidence but some studies have shown improvements in pain, sleep, fatigue and quality of life Cognitive-behavioural therapy Positive effects on coping with and control over pain Not proven to improve pain Proven to improve physical function Should be done by a trained professional Aerobic and strengthening exercises Reduce pain, increase self-efficacy, improve quality of life and reduce depression Aerobic exercise should be of low to moderate intensity, 2–5 times/week Goldenberg et al. JAMA. 2004;292:2388-2395. Brosseau et al.; Ottawa Panel Members. Phys Ther. 2008;88:873-886. Brosseau et al.; Ottawa Panel Members. Phys Ther. 2008;88:857-871.

17. Modulating Factors of FM Syndrome Pain Wallace et al. Fibromyalgia and Other Central Pain Syndromes. Lippincott Williams & Wilkins; 2005:126. FactorsMean % Exacerbating Factors Weather (cold/humid)65 Poor sleep70 Anxiety/stress61 Physical inactivity49 Noise22 Relieving Factors Local heat58 Rest54 Moderate activities46 Massage40 Stretching exercises43

18. Sleep interference can directly result from and/or contribute to FM Psychological symptoms are strongly associated with FM Management strategy for FM patients is to improve overall patient functionality Adapted from Argoff. Clin J Pain. 2007;23:15-22. Interrelationship Among Pain, Sleep Disturbance and Psychological Symptoms Paradigm of pain Functional Impairment and Fatigue PainRelated

19. Sleep Deprivation and Pain Activates, maintains central nervous system (CNS) areas responsible for awake state Dampens areas responsible for initiation and maintenance of sleep May impair healing, leading directly to pain Affects CNS areas responsible for coping mechanisms useful for dampening pain experience Chronic pain Lack of sleep Sleep disturbances may lead directly to more pain, and indirectly to a heightening of the pain experience through impairment of usual adaptive mechanisms. Call-Schmidt, Richardson. Pain Manag Nurs. 2003;4:124-133.

20. Best Evidence: FM Pain Medication MedicationMechanism of Action Effect on Pain Effect on Other Symptoms Off/on Label Indication CommentsStarting Dose and Titration Usual Maintenance Dose Amitriptyline (desipramine, doxepin, nortriptyline) TCA (NE > 5HT) +Sleep, anxiety Off Poor long term, doxepin seldom recommended, desipramine may cause insomnia (administer in morning), not well tolerated in this population 10-25 mg/day Increase weekly by 10 mg/day 50-150 mg/day CyclobenzaprineMuscle relaxant (NE) +SleepOff Poor long term10 mg 3 times/day10 mg 3 times/day (range of 20-40 mg/day in divided doses, max 60 mg/day) DuloxetineSNRI+++Depression, anxiety On 60 mg/day (can start at 30 mg for tolerability reasons with target of 60 mg/day in 1-2 weeks) 60-120 mg/day Gabapentin  2  binding: ↓neuronal excitation ++Sleep, anxiety Off 300 mg 3 times/day; increase with 300- or 400- mg capsules, or 600- or 800-mg tablets 3 times/daily 3 times/day up to 1800 mg/day PramipexoleDopamine agonist +FatigueOff Limited population studied Start 0.375 mg/day in 3 divided doses; increase gradually no more frequently than every 5-7 days 1.5 to 4.5 mg/day in equally divided doses 3 times/day Pregabalin  2  binding: ↓neuronal excitation +++Sleep, anxiety On 150 mg/day in 2 divided doses; increase by 150 mg/day after 1 week 300-450 mg in 2 divided doses TramadolOpioid agonist SNRI ++ Off 25 mg/day; increase by 25 mg/day every 3 days to 50 mg 4 times/day 50-100 mg 4 times/day GABA, γ-aminobutyric acid; NE, norepinephrine; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant (alphabetical order) +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy

21. No/Poor Evidence: FM Pain Medication MedicationMechanism of Action Rationale for UseConcern for Use BenzodiazepinesGABA increaseAnxietyAddiction Side effects CannabinoidsCB 1 receptor agonist Improves sleepLack of effectiveness in FM pain Side effects NSAIDsProstaglandin inhibition AnalgesiaNSAID-related side effects OpioidsOpioid receptor agonists AnalgesiaAddiction Side effects See new national guidelines NSAID, non-steroidal anti-inflammatory drug (alphabetical order)

22. Video 2

23. Video de-brief

24. Summary Pain is the most common symptom of FM Set realistic treatment goals Use non-pharmacologic treatments first Use medical therapies that target pain and have evidence for efficacy in FM as first-line pharmacotherapy Balance medication side effects and risk with optimizing function Menu

26. Objectives Following this module, participants will be able to: Provide a differential diagnosis of fatigue in patients with fibromyalgia (FM) Prescribe therapies that will improve fatigue in FM Assist patients in establishing reasonable treatment goals Recognize the role of an interdisciplinary team in FM management

27. Core Clinical Features of FM ACR Fibromyalgia Diagnostic Criteria. 2010. http://www.nfra.net/Diagnost.htm; Carruthers et al. J Chron Fat Synd. 2003;11:7-115; Harding. Am J Med Sci. 1998;315:367-37; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Roizenblatt et al. Arthritis Rheum. 2001;44:222-2306; Wolfe et al. Arthritis Rheum. 1995;38:19-28.http://www.nfra.net/Diagnost.htm Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance Patients describe it as physically or emotionally draining Fatigue Stiffness Stiffness in the morning is a common characteristic of FM Characterized by confusion, slowed processing of information and reaction time, difficulty in word retrieval or speaking, concentration, attention, short-term memory consolidation, disorientation Neurocognitive Impairment (“Fibro Fog”) Patients describe it as physically or emotionally draining Fatigue

28. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. Patty signed up at a local gym to take aerobic exercise classes at your suggestion. She was given a bedtime medication to improve her sleep and referred to a website that provides information for patients with FM.

29. Video 1

30. Questions 1.In patients with an established diagnosis of FM, what factors should be considered when evaluating fatigue? 2.What non-medication approach would you take with Patty? 3.What FM medications target fatigue? 4.How could an interdisciplinary team (your own team or resources in your community) assist in the management of patients with FM? What other healthcare professional could help? Take the time to answer each of the questions

31. Symptoms of FM Pain, fatigue and sleep disturbance are present in at least 86% of patients* 0 20 40 60 80 100 100% 96% 86% 72% 60% 56% 52% 46% 42% 41% 32% 20% Muscular pain FatigueInsomniaJoint pains Head- aches Restless legs Numbness and tingling Impaired memory Leg cramps Impaired Concen- tration Nervous- ness Major depression *United States data ACR 1990 Fibromyalgia Diagnostic Criteria. National Fibromyalgia Research Association Web site http://www.nfra.net/Diagnost.htm.http://www.nfra.net/Diagnost.htm

32. Things to Consider when FM Patients Complain of Fatigue 1.Sleep disturbance 2.Uncontrolled pain 3.Depression 4.Unrealistic expectations 5.“Stress” caused by illness 6.Medication side effects (especially polypharmacy) 7.Deconditioning 8.Unrecognized new illness* * Avoid the trap of re-investigating the patient with firmly diagnosed FM, but remember: eventually all FM patients will get another disease!

33. 1. Musculoskeletal (19.4%) 2. Psychosocial (16.5%) 3. Gastrointestinal (8.1%) 4. Neurological (6.7%) 5. General (4.9%) 6. Respiratory (4.9%) 7. Endocrine (2.8%) 8. Cardiovascular (1.9%) 9. Menopause (1.1%) 10. Malignancy (.7%) 46.9% of those with the initial presentation of fatigue and with no diagnosis made at the time of presentation had, at the end of one year, one or more of these diagnoses that could possibly be the cause of their fatigue. Fatigue in Primary Care – One-Year Follow-Up Note that of musculoskeletal complaints, most were deemed non-specific. Documentation at initiation of study indicated that 24.1% of patients had depressive symptoms. Diagnosis of depression was made in 4.9% of subjects at one year. Nijrolder et al. CMAJ. 2009;181:683-687.

34. Sleep interference can directly result from and/or contribute to FM Psychological symptoms are strongly associated with FM Management strategy for FM patients is to improve overall patient functionality Adapted from Argoff. Clin J Pain. 2007;23:15-22 Interrelationship Among Pain, Sleep Disturbance and Psychological Symptoms Paradigm of pain Functional Impairment and Fatigue PainRelated

35. Sleep Deprivation and Pain Activates, maintains central nervous system (CNS) areas responsible for awake state Dampens areas responsible for initiation and maintenance of sleep May impair healing, leading directly to pain Affects CNS areas responsible for coping mechanisms useful for dampening pain experience Chronic pain Lack of sleep Sleep disturbances may lead directly to more pain, and indirectly to a heightening of the pain experience through impairment of usual adaptive mechanisms. Call-Schmidt, Richardson. Pain Manag Nurs. 2003;4:124-133

36. Utility of FM Medications Targeting Fatigue There are no generally accepted, on-label medications that improve the fatigue associated with FM Physical activity is the only non-pharmacologic strategy proven to reduce fatigue

37. What is helpful for complaints of fatigue? Improvement of sleep hygiene Moderate physical activity Pacing Realistic goal setting Healthy eating Cognitive behavioral therapy (CBT) Lera et al. J Psychosom Res. 2009;67:433-441. Rossy et al. Ann Behav Med. 1999;21:180-191. Williams. Best Pract Res Clin Rheumatol. 2003;17:649-665.

38. Medications with Anti-fatigue Properties MedicationMechanism of Action Effect on Fatigue Effect on Other Symptoms Comments BupropionNE Dopamine -DepressionMore “energizing” antidepressant DuloxetineSNRI+Pain, depression, anxiety Improvement in fatigue as secondary endpoint ModafinilDopamine NE + Open label small study PramipexoleDopamine agonist + PainOff label - limited population studied Stimulants (methylphenidate, dextroamphetamine) NE Dopamine - No evidence Addiction properties so caution (alphabetical order) +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy NE, norepinephrine; SNRI, serotonin-norepinephrine reuptake inhibitor

39. Video 2

40. Video de-brief

41. Summary When fatigue is the primary complaint, evaluate sleep and pain control, and rule out depression Use of medications may improve fatigue Help patients set realistic goals for improvement of fatigue Important role of non-pharmacologic interventions, especially physical activities Menu

43. Objectives Following this module, participants will be able to: Recognize the relationship between sleep restoration and symptom improvement in patients with fibromyalgia (FM) Provide non-pharmacologic therapies to improve sleep disturbance Prescribe medications that target sleep and other FM symptoms Recognize the role of the interdisciplinary team in FM management

44. Core Clinical Features of FM ACR Fibromyalgia Diagnostic Criteria. 2010. http://www.nfra.net/Diagnost.htm; Carruthers et al. J Chron Fat Synd. 2003;11:7-115; Harding. Am J Med Sci. 1998;315:367-37; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Roizenblatt et al. Arthritis Rheum. 2001;44:222-2306; Wolfe et al. Arthritis Rheum. 1995;38:19-28.http://www.nfra.net/Diagnost.htm Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance Patients describe it as physically or emotionally draining Fatigue Stiffness Stiffness in the morning is a common characteristic of FM Characterized by confusion, slowed processing of information and reaction time, difficulty in word retrieval or speaking, concentration, attention, short-term memory consolidation, disorientation Neurocognitive Impairment (“Fibro Fog”) Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance

45. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. Patty was advised to attend a local yoga studio, which has a special FM class. She was given a morning medication that targeted mood and pain. She was encouraged to review a website that provides information for patients with FM.

46. Video 1

47. Questions 1.What elements should you consider when evaluating Patty’s sleep problems? 2.What non-medication approach would you take with Patty? 3.What FM medications improve sleep problems? 4.How could an interdisciplinary team (your own team or resources in your community) assist in the management of patients with FM? Take the time to answer each of the questions

48. Symptoms of FM Pain, fatigue and sleep disturbance are present in at least 86% of patients* 0 20 40 60 80 100 100% 96% 86% 72% 60% 56% 52% 46% 42% 41% 32% 20% Muscular pain FatigueInsomniaJoint pains Head- aches Restless legs Numbness and tingling Impaired memory Leg cramps Impaired Concen- tration Nervous- ness Major depression * United States data ACR 1990 Fibromyalgia Diagnostic Criteria. National Fibromyalgia Research Association Web site http://www.nfra.net/Diagnost.htm.http://www.nfra.net/Diagnost.htm

49. Pain Poor sleep hygiene Medication side effects (including caffeine) Anxiety/depression/bipolar disorder Other sleep disorders (restless leg syndrome, obstructive sleep apnea, etc.) Differential Diagnoses to Consider with Sleep Disorders

50. Sleep interference can directly result from and/or contribute to FM Psychological symptoms are strongly associated with FM Management strategy for FM patients is to improve overall patient functionality Adapted from Argoff. Clin J Pain. 2007;23:15-22. Interrelationship Among Pain, Sleep Disturbance and Psychological Symptoms Paradigm of pain Functional Impairment and Fatigue PainRelated

51. Sleep Deprivation and Pain Activates, maintains central nervous system (CNS) areas responsible for awake state Dampens areas responsible for initiation and maintenance of sleep May impair healing, leading directly to pain Affects CNS areas responsible for coping mechanisms useful for dampening pain experience Chronic pain Lack of sleep Sleep disturbances may lead directly to more pain, and indirectly to a heightening of the pain experience through impairment of usual adaptive mechanisms. Call-Schmidt, Richardson. Pain Manag Nurs 2003;4:124-133.

52. Pain Leads to Sleep Disruption Result of noxious pain stimuli = arousal Decrease in delta waves Increase in alpha waves In FM: the structure of the sleep is modified and there is fragmentation of sleep Drewes et al. Sleep. 1997;20:632-640.

53. Non-pharmacologic Interventions to Improve Sleep 1.Avoid stimulants 2.Regular time to go to bed and to rise 3.Avoid napping through day 4.Regular AM exercise 5.Bed is for sleep and sex 6.Relaxation before bed 7.Sleep handout for patients www.tufts.edu/med/phfm/pdf/fm-handouts/SleepHygiene.pdf

54. Medications and Effects on Sleep MedicationEffect on SleepEffect on Pain Amitriptyline (desipramine, doxepin, nortriptyline) ++++ (poor long-term) Atypical antipsychotics+++± Benzodiazepines+++- Cannabinoids++++ Cyclobenzaprine++++ (poor long-term) Duloxetine++++ Gabapentin++ Pregabalin+++ Zopiclone+++- (alphabetical order) Evidence for effect on sleep is mostly within non-pain patients and has been collected by polysomnography. The only evidence from patients with pain is with pregabalin through patient diaries and Medical Outcomes Study Sleep scores +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy

55. Video 2

56. Video de-brief

57. Summary Rule out secondary causes of sleep disorders Consider lifestyle modification as a first step to manage sleep problems Consider pain/sleep/fatigue cycle when considering therapies Use medical therapies that target sleep when it is prevalent disabling symptom Menu

59. Objectives Following this module, participants will be able to: Differentiate fibromyalgia (FM) from depression Prescribe therapies that will improve both FM and depression Have an approach to explaining depression and FM to patients Use an interdisciplinary team to manage patients with FM

60. Core Clinical Features of FM ACR Fibromyalgia Diagnostic Criteria. 2010. http://www.nfra.net/Diagnost.htm; Carruthers et al. J Chron Fat Synd. 2003;11:7-115; Harding. Am J Med Sci. 1998;315:367-37; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Roizenblatt et al. Arthritis Rheum. 2001;44:222-2306; Wolfe et al. Arthritis Rheum. 1995;38:19-28.http://www.nfra.net/Diagnost.htm Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance Patients describe it as physically or emotionally draining Fatigue Stiffness Stiffness in the morning is a common characteristic of FM Characterized by confusion, slowed processing of information and reaction time, difficulty in word retrieval or speaking, concentration, attention, short-term memory consolidation, disorientation Neurocognitive Impairment (“Fibro Fog”)

61. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. Patty was referred to a “Living with FM” lifestyle program run by a local physiotherapist. She was advised to work on lifestyle and sleep hygiene, and to use a simple over-the-counter analgesic for pain control. She presents for follow-up complaining that the interventions are “not effective.”

62. Video 1

63. Questions 1.Is FM just depression with pain? 2.What treatment modalities may be indicated in this patient? 3.How would you convince Patty that an antidepressant medication would be a good choice? 4.How could an interdisciplinary team (your own team or resources in your community) assist in the management of patients with FM? Take the time to answer each of the questions

64. Symptoms in FM Syndrome SYMPTOMSMEAN (%) Musculoskeletal Pain at multiple sites100 Stiffness76 “Hurt all over”62 Swollen feeling in tissues52 Non-musculoskeletal General fatigue87 Morning fatigue75 Sleep difficulties72 Paresthesia54 Dizziness/vertigo59 Tinnitus17 Sicca symptoms15 Raynaud phenomenon14 SYMPTOMSMEAN (%) Non-musculoskeletal Anxiety60 Mental stress61 Depression37 Cognitive dysfunction61 Selected Associated Syndromes Headaches54 Dysmenorrhea43 Irritable bowel syndrome38 Restless legs syndrome31 Female urethral syndrome 15 Wallace et al. Fibromyalgia and Other Central Pain Syndromes. Lippincott Williams & Wilkins; 2005:126.

65. Anxiety disorder Any psychiatric disorder Mood disorder 100 80 60 40 20 0 100 80 60 40 20 0 How Patients with Psychiatric Disorders Initially Present to Primary Care Physicians 1 Psychological 83% Somatic 17% Strong Correlation Between Number of Physical Symptoms and Prevalence of Psychiatric Disorders 2 The more physical complaints there are, the more likely there is a psychiatric problem. Patients with psychiatric disorders (%) Number of physical complaints 2-34-56-8 ≥9 Most people with psychological problems go to their family doctor with a physical complaint rather than recognizing that they have a form of mental distress. 1. Kirmayer et al. Am J Psychiatry. 1993;150:734-741. 2. Kroenke et al. Arch Fam Med. 1994; 3:774-779. 0-1

66. SymptomPsychiatricHealthy Tired, lack of energy85% 40% Headache, head pains64%48% Dizzy or faint60% 14% Parts of body felt weak57%23% Muscle pains, aches, rheumatism53% 27% Stomach pains51%20% Chest pains46% 14% Adapted from Kellner R and Sheffield BF. Am J Psychiatry. 1973;130:102-105. Somatic Symptoms Common in Psychiatric Patients

67. Maintain a High Index of Suspicion for the Diagnosis of Major Depressive Disorder In patients with: Multiple physical symptoms Frequent visits and thick charts Poor sleep, fatigue Chronic pain (including FM, migraines, irritable bowel syndrome) Anxiety disorders Substance-use disorders Attention-deficit/hyperactivity disorder Type II diabetes, ischemic heart disease, cerebrovascular accidents, cancer, osteoporosis

68. Mood Disorders in FM At time of diagnosis, approximately 20%–40% of individuals with FM have an identifiable current mood disorder (e.g., depression or anxiety) Lifetime prevalence of depression: 74% Lifetime prevalence of anxiety disorder: 60% In many cases, depression or anxiety may be the result of chronic pain Katon et al. Ann Intern Med. 2001;134:917-925. Boissevain et al. Pain. 1991;45:227-238. Boissevain et al. Pain. 1991;45:239-248. Giesecke et al. Arthritis Rheum. 2003;48:2916–2922. Arnold et al. Arthritis Rheum. 2004;50:944–952. Fishbain et al. Clin J Pain. 1997;13:116–137.

69. Strategy for Explaining Depression Reinforce neurobiological basis of depression Acknowledge that chronic pain and depression frequently co-exist Use the symptom complex for depression – SIGECAPS – to help patients understand symptom grouping Encourage bibliotherapy to reinforce concepts Use other members of healthcare team to assist in psychoeducation SIGECAPS, mnemonic mnemonic for symptoms of major depression and dysthymia (sleep disorder, interest deficit, guilt, energy deficit, concentration deficit, appetite disorder, psychomotor retardation or agitation, suicidality)

70. Non-pharmacologic Treatment Evidence for effectiveness of cognitive behavioral therapy (CBT) for both depression and FM Bennett et al. Nat Clin Pract Rheumatol. 2006;2:416-424. Whitfield et al. Advances Psychiat Treat. 2003;9:21-30.

71. Medications for FM that Have Mood Regulation and Anxiolytic Properties MedicationMechanism of Action Effect on Mood/Anxiety Effect on Other Symptoms Off/on- Label Indication For FM Comments Amitriptyline (desipramine, doxepin, nortriptyline) TCA (NE > 5HT) +Pain, sleepOffFM doses < usual antidepressant dose Bupropion Atypical anti- depressant ++FatigueOffMore “energizing” antidepressant Duloxetine SNRI+++PainOn Gabapentin  2  binding: ↓neuronal excitation ++ Pain, sleepOffAddress anxiety reduction properties Pregabalin  2  binding: ↓neuronal excitation +++Pain, sleepOnAddress anxiety reduction properties SertralineSSRI++PainOffCompared versus physical therapy VenlafaxineSNRI > SSRI++PainOffOpen-label small studies, limited effect on FM pain GABA, γ-aminobutyric acid; NE, norepinephrine; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant (alphabetical order) +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy

72. Video 2

73. Video de-brief

74. Summary FM is common, depression is common. They frequently occur together but are separate disorders Patient education is key Use an interdisciplinary team and multimodal therapies to help treat FM and comorbid depression Use pharmacologic and non-pharmacologic (especially CBT) strategies Therapies that may treat both include CBT and antidepressants with analgesic properties Menu

76. Objectives Following this module, participants will be able to: Give the prevalence demographics of fibromyalgia (FM) Make a diagnosis of FM Order appropriate investigations for patients with suspected FM Provide a differential diagnosis for patients presenting with widespread pain, fatigue and sleep problems

77. Case Study Patty is a 32-year-old woman in your practice History: Under your care for 10 years Unremarkable past history Slipped on ice 4 months ago and has had progressive generalized pain and fatigue Saw a locum 2 weeks ago who ran a battery of tests for multiple symptoms of generalized pain, fatigue and sleep problems

78. Video 1

79. Questions 1.What is the incidence and gender distribution of FM? 2.How do you make the diagnosis of FM? 3.What are the differential diagnoses in this patient? 4.What investigations would you have ordered 2 weeks ago? Take the time to answer each of the questions

80. Prevalence of FM FM occurs in all ages, both sexes and all cultures, but occurs more frequently in: Women Patients between the ages of 35–60 years In Canada: FM affects an estimated 4.9% of adult women and 1.6% of adult men Female-to-male ratio of approximately 3:1 Cardiel et al. Clin Exp Rheumatol. 2002;20:617-624; Carmona et al. Ann Rheum Dis. 2001;60:1040-1045; Lawrence et al. Arthritis Rheum. 1998;41:778- 799; Lindell et al. Scand J Prim Health Care. 2000;18:149-153; Neumann et al. Curr Pain Headache Rep. 2003;7:362-368; Prescott et al. Scand J Rheumatol. 1993;22:233-237; White et al. J Rheumatol. 1999; 26:1570-1576; Wolfe F. J Musculoskeletal Pain. 1993;3:137-148; Wolfe et al. Arthritis Rheum. 1995;38:19-28;.

81. Core Clinical Features of FM ACR Fibromyalgia Diagnostic Criteria. 2010. http://www.nfra.net/Diagnost.htm; Carruthers et al. J Chron Fat Synd. 2003;11:7-115; Harding. Am J Med Sci. 1998;315:367-37; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Roizenblatt et al. Arthritis Rheum. 2001;44:222-2306; Wolfe et al. Arthritis Rheum. 1995;38:19-28.http://www.nfra.net/Diagnost.htm Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting Presence of tender points Widespread Pain Characterized by non-restorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Sleep Disturbance Patients describe it as physically or emotionally draining Fatigue Stiffness Stiffness in the morning is a common characteristic of FM Characterized by confusion, slowed processing of information and reaction time, difficulty in word retrieval or speaking, concentration, attention, short-term memory consolidation, disorientation Neurocognitive Impairment (“Fibro Fog”)

82. Symptoms of FM Pain, fatigue and sleep disturbance are present in at least 86% of patients* *United States data 0 20 40 60 80 100 100% 96% 86% 72% 60% 56% 52% 46% 42% 41% 32% 20% Muscular pain FatigueInsomniaJoint pains Head- aches Restless legs Numbness and tingling Impaired memory Leg cramps Impaired Concen- tration Nervous- ness Major depression ACR 1990 Fibromyalgia Diagnostic Criteria. National Fibromyalgia Research Association Web site http://www.nfra.net/Diagnost.htm.http://www.nfra.net/Diagnost.htm

83. Mood Disorders in FM At time of diagnosis, approximately 20%-40% of individuals with FM have an identifiable current mood disorder (e.g., depression or anxiety) Lifetime prevalence of depression: 74% Lifetime prevalence of anxiety disorder: 60% In many cases, depression or anxiety may be the result of chronic pain Arnold et al. Arthritis Rheum. 2004;50:944–952; Boissevain et al. Pain. 1991;45:227-238; Boissevain et al. Pain. 1991;45:239-248; Fishbain et al. Clin J Pain. 1997;13:116–137; Giesecke et al. Arthritis Rheum. 2003;48:2916–2922; Katon et al. Ann Intern Med. 2001;134:917-925.

84. Stressors Some triggering event may trigger FM but is not a prerequisite In many cases, onset of FM is gradual, with no identifiable trigger Stressors that may trigger FM Peripheral pain syndromes, physical trauma, infections (e.g., parvovirus, Epstein-Barr virus, Lyme disease, Q fever), psychological stress/distress, including sleep disturbances The development of FM after a precipitating event may represent the onset of a prolonged and disabling pain syndrome with considerable social and economic implications Greenfield et al. Arthritis Rheum. 1992;35:678-681. McLean et al. Med Hypotheses. 2004;63:653-658.

85. Trigger FactorsAssociated Factors* Cold 015 Stress 935 Emotions 535 Overwork 022 Trauma 24 Surgery 413 Death in the family 013 Family problems 225 Fatigue 023 No cause/association 555 FM as a Consequence of Trauma Factors Triggering FM or Associated with its Onset (n=136) In most cases of FM, there is no predisposing trigger. Adapted from Wolfe F. Am J Med. 1986;81:7-14. *More than one factor possible for the same patient

86. Diagnosing FM: Overview Patient history of FM or related conditions Personal history Family history Physical examination Most important to rule out other conditions Differential diagnosis Clinical/laboratory evaluation to exclude other conditions such as: Osteoarthritis, rheumatoid arthritis, polymyalgia rheumatica (PMR), hypothyroidism, lupus and Sjögren’s syndrome Note: Extensive lab evaluation is usually not necessary to rule out FM, In some cases, a thyroid-stimulating hormone test may be called for. PMR is usually not a problem as it seldom occurs under the age of 60, whereas the onset of FM after 65 is rare. Mease. J Rheumatol. 2005;32(suppl 75):6-21; Wolfe et al. Arthritis Rheum. 1990;33:160-172.

87. Evolution of FM Diagnosis Evaluation of tender points Identification of symptoms complex New Canadian guidelines being developed

88. Assessment of FM: American College of Rheumatology (ACR) Classification Criteria (1990) History of widespread pain that has been present for at least 3 months (ALL of the following should be present): Pain on both sides of the body Pain above and below the waist Axial skeletal pain Pain in at least 11 of 18 tender point sites on digital palpation Wolf et al. Arthritis Rheum. 1990;33:160-172. ACR criteria are both sensitive (88.4%) and specific (81.1%)

89. ACR New Proposed Diagnostic Criteria for FM – 2010 (1) FM can be diagnosed if: Symptoms for at least 3 months No other condition to explain pain Pain + associated symptoms Wolfe et al. Arthritis Care Res (Hoboken). 2010;62:600-610.

90. ACR New Proposed Diagnostic Criteria for FM – 2010 (2) Associated symptoms include: Unrefreshed sleep Cognitive symptoms Fatigue Other somatic symptoms Wolfe et al. Arthritis Care Res (Hoboken). 2010;62:600-610.

91. Summary FM is a common disease of middle age with a female-to-male ratio of 3:1 Simple investigations and history will exclude other rheumatologic or psychiatric conditions The 4 cardinal symptoms of FM include widespread pain, fatigue, sleep disturbance and cognitive slowing The current diagnosis of FM is based on widespread pain plus associated symptom cluster with a physical exam to exclude other conditions Menu

93. Objectives Following this module, participants will be able to : Explain the known pathophysiology of fibromyalgia (FM) Provide the natural history of FM Negotiate and explain the diagnosis of FM Use multidisciplinary and other resources to help educate patients around the diagnosis of FM

94. Case Study Patty is a 32-year-old woman in your practice History: Under your care for 10 years Unremarkable past history Slipped on ice 4 months ago and has had progressive generalized pain and fatigue Saw a locum 2 weeks ago who ran a battery of tests for multiple symptoms of generalized pain, fatigue and sleep problems Clinical exam confirms diagnosis of FM

95. Video 1

96. Questions 1.What is FM? How would you explain it to Patty? 2.What is the natural history of FM? 3.Is it better to “label” Patty with the diagnosis of FM? 4.What other strategies could you use to educate Patty about the disease? Take the time to answer each of the questions

97. Pathogenesis of FM: Overview FM is a condition of global dysregulation of pain processing Central sensitization is one component Mechanisms of central sensitization Excitatory mechanisms Inhibitory mechanisms Price DD, Staud R. J Rheumatol. 2005;32 (Suppl 75):22-28.

98. Pathophysiological Changes in FM Increased levels of substance P (>3x) in patients with FM Functional magnetic resonance imaging (fMRI) studies show a marked regional increase in cerebral blood flow following a painful stimulus in patients with FM compared to controls not suffering FM Deficit in the endogenous pain inhibitory systems noted in FM patients Vaerøy et al. Pain. 1988;32:21-26.; Russell et al. Arthritis Rheum. 1994;37:1593-1601. ; Russell et al. In: Russell, ed. Myopain ’95: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia. San Antonio, Tex; July 30-August 3, 1995.Gracely et al. Arthritis Rheum. 2002;46:1333-1343.; Julien et al. Pain. 2005;114:295-302.

99. Diagnosis Can Improve Patient Satisfaction Diagnosis of FM improves health satisfaction White et al conducted a prospective, community comparison of FM patients in Canada that revealed significantly improved scores 36 months post-diagnosis Patients self-reported health satisfaction on a 5-point Likert scale Improvement in Patient Health Satisfaction Patient health satisfaction 3 2.2* 0 1 2 3 4 Baseline Post-diagnosis Improvement 5 *Statistically significant versus baseline (confidence interval -1.2, -0.4) Goldenberg et al. JAMA. 2004;292:2388-2395. White et al. Arthritis Rheum. 2002;47:260-265.

100. Health Economic Consequences Related to the Diagnosis of FM Tests and Imaging Referrals General Practitioner Visits Drugs Annemans et al. Arthritis Rheum 2008;58:895-902. United Kingdom figures

101. Fate of Patients with FM Reassure patients that FM is not progressive and that symptoms remain stable over time 1 50% were moderately to greatly improved (3 year follow-up) 2 The baseline predictors for a favorable outcome: younger age and less sleep disturbance 2 Successful management requires an upbeat, optimistic approach and EARLY initiation of effective, individualized therapy Therefore, it is important to manage patient’s expectations 1. Kennedy et al. Arthritis Rheum. 1996;39:682-685. 2. Fitzcharles et al. J Rheumatol. 2003;30:154-159.

102. Video 2

103. Video de-brief

104. Some Tips on Providing the Diagnosis Be specific about the diagnosis Be positive about the diagnosis Promote and encourage patient self-efficacy around the disease but... Set realistic expectations Emphasize no cure but improved control of symptoms usually possible Active treatments generally superior to passive treatments

105. Other Useful Websites/Patient Information National ME/FM Action Network: http://www.mefmaction.net Arthritis Society of Canada: www.arthritis.cawww.arthritis.ca Patient workbooks/materials Starlanyl D, Copeland ME. Fibromyalgia & Chronic Myofascial Pain Syndrome: A Survival Manual. 2 nd ed. Oakland, CA : New Harbinger Publications; 2001. Fennell PA. The Chronic Illness Workbook: Strategies And Solutions for Taking Back Your Life. 2 nd ed. Latham, NY: Albany Health Management Publishing; 2007. Bested AC, Logan AC. Hope and Help for Chronic Fatigue Syndrome and Fibromyalgia. 2 nd ed. Nashville, TN: Cumberland House; 2008.

106. Local Resources [Facilitators to include list of local FM resources for patients/physicians]

107. Summary FM is a neurobiological dysfunction Providing a positive diagnosis improves health outcomes and reduces costs The natural history of FM is variable. Significant numbers of patients will improve Use Internet and written resources and other members of a multidisciplinary team to educate patients Menu

109. Objectives Following this module, participants will be able to: Assess motivation in patients with fibromyalgia (FM) Use simple strategies to increase patients’ readiness to incorporate non-pharmacologic and lifestyle Give evidence-based, non-pharmacologic interventions as treatment for FM Recognize the role of an interdisciplinary team in FM management

110. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. Patty was advised to attend a local “new movement class” targeting de-conditioned patients to increase physical activity. She was also prescribed a medication that would target pain – her most disabling symptom.

111. Video 1

112. Questions 1.What non-pharmacologic interventions have been shown to help with FM? 2.How might you help to motivate Patty? 3.How could your interdisciplinary team (your own team or resources in your community) assist in the management of patients with FM? Take the time to answer each of the questions

113. Management of FM: Recommended Treatment Approach Multidisciplinary therapy individualized to patients’ symptoms and presentation is recommended A combination of non-pharmacologic and pharmacologic therapies may benefit most patients *Limited evidence for efficacy exists Balneotherapy: treatment of disease or health conditions by bathing Non-pharmacologic Aerobic exercise Cognitive behavioral therapy (CBT) Patient education Strength training Acupuncture* Biofeedback* Balneotherapy* Goldenberg et al. JAMA. 2004;292:2388-2395.

114. Non-pharmacologic Treatments with Demonstrated Efficacy Currently in Use CBT Positive effects on coping with and control over pain Not proven to improve pain Proven to improve physical function Should be done by a trained professional Aerobic and strengthening exercises Reduce pain, increase self-efficacy, improve quality of life and reduce depression Aerobic exercise should be of low-to-moderate intensity, 2–5 times/week Patient education Conflicting evidence but some studies have shown improvements in pain, sleep, fatigue and quality of life Goldenberg et al. JAMA. 2004;292:2388-2395. Brosseau L, et al. Phys Ther. 2008;88:857-71. Brosseau L, et al. Phys Ther. 2008;88:873-86.

115. Alternative/Chiropractic treatments for FM Strong evidence supports aerobic exercise and CBT Moderate evidence supports massage, muscle strength training, acupuncture and spa therapy (balneotherapy) Limited evidence supports spinal manipulation, movement/body awareness, vitamins, herbs and dietary modification Schneider et al. J Manipulative Physiol Ther. 2009;32:25-40.

116. Useful Websites/Patient Information National ME/FM Action Network: http://www.mefmaction.net Arthritis Society of Canada: www.arthritis.cawww.arthritis.ca Patient workbooks/materials: Starlanyl D, Copeland ME. Fibromyalgia & Chronic Myofascial Pain Syndrome: A Survival Manual. 2 nd ed. Oakland, CA : New Harbinger Publications; 2001. Fennell PA. The Chronic Illness Workbook: Strategies And Solutions for Taking Back Your Life. 2 nd ed. Latham, NY: Albany Health Management Publishing; 2007. Bested AC, Logan AC. Hope and Help for Chronic Fatigue Syndrome and Fibromyalgia. 2 nd ed. Nashville, TN: Cumberland House; 2008. Local resources

117. Helping patients embrace lifestyle choices — improving self-efficacy

118. Conviction and Confidence: A Model for Successful Interventions Patient conviction (i.e., sense of the patient’s personal, emotional recognition of the benefits of changing a behaviour) “Is increasing your physical activity a priority for you?” Patient confidence (i.e., sense of the patient’s ability to modify a behaviour) “If you did decide to become physically active, how confident are you that you would be able to follow though?” Keller VF, White KM. J Clin Outcomes Manage. 1997;4:33-36. Miller WR, Rollnick S. Motivational interviewing. New York NY: Guilford Press; 1991.

119. LACK OF KNOWLEDGE CYNICISM FRUSTRATION SKEPTICISM C O N F I D E N C E C O N V I C T I O N UNWAVERINGPOWERLESS AMBIVALENT CONVINCED 0 10 SUCCESS EMPOWERED (Benefits) (Barriers) Conviction – Confidence Model 10 Adapted from Keller VF, White KM. J Clin Outcomes Manage. 1997;4:33-36.; Miller WR, Rollnick S. Motivational interviewing. New York NY: Guilford Press; 1991.

120. How to Increase Conviction Get patients to articulate benefits of change

121. How to Increase Confidence Identify barriers to change and help patients overcome those barriers by identifying their own solutions

122. A Model for Successful Interventions Keller VF, White KM. J Clin Outcomes Manage. 1997;4:33-36.; Miller WR, Rollnick S. Motivational interviewing. New York NY: Guilford Press; 1991. Conviction (Benefits) Convinced Ambivalent 0 10 Confidence Powerless(Barriers)Unwavering 10 Pre-contemplation Contemplation Preparation Empowered Skepticism Lack of knowledge Cynicism Frustration Success Action Patty

123. Video 2

124. Video de-brief

125. Summary Non-pharmacologic therapies are an important first-line treatment for patients with FM Compliance to lifestyle interventions can be increased by assessing and intervening with motivational interviewing techniques The use of multidisciplinary resources can improve outcomes and facilitate time-efficient treatment Menu

127. Objectives Following this module, participants will be able to: Link the medications useful in treatment of fibromyalgia (FM) Match medication properties and side effects with therapeutic targets for patients with FM Articulate safety issues with medications commonly used to treat FM

128. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. She presented with a typical symptom complex: generalized pain, fatigue, non-restorative broken sleep and mental fogging. You asked her after the first visit to review medication options with a pharmacist who works as part of your interdisciplinary team.

129. Exercise Complete the worksheet with your partner For each class of medication, indicate what is the effect of each symptom, using -, +, ++ or +++, and describe the most common side effects. *Medication with official indication in fibromyalgia ClassMedicationsOverall FM PainFatigueSleepDepression/ anxiety Most common side effects seen in patients, based on your experience Antiepileptic analgesics Pregabalin* Gabapentin Atypical antidepressants Bupropion Atypical antipsychotics Benzodiazepines Cannabinoids Dopamine agonistPramipexole Dopamine NEModafinil Muscle relaxant (NE)Cyclobenzaprine NSAIDs Opioids Opioid agonist SNRITramadol Psycho-stimulantsDextroamphetamine, methylphenidate SNRIDuloxetine* Venlafaxine SSRISertraline TCAAmitriptyline (desipramine, doxepin, nortriptyline) Zopiclone

130. Video 1

131. Video de-brief

132. Medical Management of FM: Considerations Don’t set unrealistic goals; target functional improvement Important to manage patient’s expectations Keep the patient involved in treatment decisions Balance efficacy with side effects Avoid rapid dose escalation: start low, go slow!

133. Medical Management of FM: Considerations (cont’d) Use opioids with caution; keep doses low Refer to the new Canadian practice guideline on use of chronic opioid therapy for non-cancer pain Always augment with non-medical therapy Polypharmacy may be necessary, but keep doses low and be mindful of side effects and function

134. Polypharmacy Often necessary for symptom control May exacerbate or cause some of the target symptoms of FM (cognitive impairment, sleep disturbance, fatigue) Be aware of drug interactions (e.g., serotonin syndrome)

135. Best Evidence: Medication Options in FM MedicationMechanism of Action Efficacy in Overall FM Management Effect on Major Symptoms Off/On- Label Indication Amitriptyline (desipramine, doxepin, nortriptyline) TCA (NE > 5HT) +Pain, sleep, anxiety (poor long term) Off DuloxetineSNRI+++Pain, depression, anxiety On Gabapentin  2  binding: ↓neuronal excitation ++Pain, sleep, anxiety Off Pregabalin  2  binding: ↓neuronal excitation +++Pain, sleep, anxiety On TramadolOpioid agonist SNRI ++PainOff GABA, γ-aminobutyric acid; NE, norepinephrine; SNRI, serotonin-norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant (alphabetical order) +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy

136. Some Evidence: Medication Options in FM MedicationMechanism of Action Efficacy in Overall FM Management Effect on Major Symptoms Off/on- Label Indication Comments Atypical antipsychotics Dopamine ±SleepOffOpen label study CannabinoidsCB 1 receptor agonist +SleepOff Lack of effectiveness in FM pain Cyclobenza- prine Muscle relaxant (NE) +Pain, sleep (poor long term) Off PramipexoleDopamine agonist +Pain, fatigueOffLimited population studied SertralineSSRI±Pain, depression OffCompared versus physical therapy VenlafaxineSNRI > SSRI+Pain, depression, anxiety OffLimited FM study +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy SSRI, selective serotonin reuptake inhibitor (alphabetical order)

137. No Evidence: Medication Options in FM MedicationMechanism of Action Rationale for Use Concern for Use BenzodiazepinesGABA increaseAnxietyAddiction Side effects NSAIDsProstaglandin inhibition AnalgesiaNSAID-related side effects OpioidsOpioid receptor agonists AnalgesiaAddiction Side effects Stimulants (dextroamphetamine, methylphenidate) NE Dopamine FatigueDiversion Abuse ZopicloneGABASleep NSAID, non-steroidal anti-inflammatory drug +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy (alphabetical order)

138. Video 2

139. Video de-brief

140. Summary Establish realistic treatment goals Important to manage patient expectations Chose medications that target the most troublesome symptoms Start low, go slow – reassure Use polypharmacy with care Opioids are controversial Menu

142. Objectives Following this module, participants will be able to: Differentiate the concepts of functional remission versus full symptom remission Establish realistic therapeutic goals with patients Use interdisciplinary team resources to manage patients with fibromyalgia (FM)

143. Case Study Patty is a 32-year-old patient in your practice who was diagnosed with FM that appeared to start after she slipped on some ice. After communicating the diagnosis to her, you referred her to a local FM lifestyle program. She was also started on a medication targeting sleep restoration, her most debilitating symptom at presentation. She presents for a follow-up visit.

144. Video 1

145. Questions 1.How do you monitor the effectiveness of treatments? 2.What is the realistic endpoint of therapy for FM? Is full remission of symptoms a reasonable goal? 3.How do you explain or negotiate therapeutic goals to patients? 4.How could you use an interdisciplinary team (your own team or resources in your community) to manage your patients with FM? Take the time to answer each of the questions

146. Monitoring Treatment Currently, there is no currently validated acceptable tool for assessing response to treatment Consider evaluation of patients with FM in these dimensions: Pain Fatigue Sleep Functionality (physical and psychological) Mood

147. Functional versus Symptom Remission Symptomatic remission is resolution of all symptoms associated with the condition Functional remission is improvement of symptoms to the point where patients can maximize function (vocational, interpersonal, social) Although most patients with FM will not attain full symptom remission in the short term, the natural history of FM is more positive

148. Fate of Patients with FM Reassure patients that FM is not progressive and that symptoms remain stable over time 1 50% were moderately to greatly improved (3 year follow-up) 2 The baseline predictors for a favorable outcome: younger age and less sleep disturbance 2 Successful management requires an upbeat, optimistic approach and EARLY initiation of effective, individualized therapy 1. Kennedy et al. Arthritis Rheum. 1996;39:682-685. 2. Fitzcharles et al. J Rheumatol. 2003;30:154-159.

149. Strategy for Management Explain the long-term nature of FM Reassure the patient that it is not life-threatening Choose therapies that target the most disabling symptom(s) Emphasize functional improvements Balance medication side effects with improvement in function

150. Medications Options for FM (1) MedicationMechanism of Action Efficacy in Overall FM Management Effect on major symptoms Off/on- Label Indication Comments Amitriptyline (desipramine, nortriptyline, doxepin) TCA (NE > 5HT) +Pain, sleep, anxiety OffFM dose < usual antidepressant dose Poor long term CannabinoidsCB 1 receptor agonist +SleepOffLack of effectiveness in FM pain CyclobenzaprineMuscle relaxant (NE) +Pain, sleepOffPoor long term DuloxetineSNRI+++Pain, depression, anxiety On +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy NE, norepinephrine; SNRI, serotonin-norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant (alphabetical order)

151. Medications Options For FM (2) MedicationMechanism of Action Efficacy in Overall FM Management Effect on major symptoms Off/on-Label Indication Comments Gabapentin  2  binding: ↓neuronal excitation ++Pain, sleep, anxiety Off ModafinilDopamine NE +FatigueOffOpen label small study PramipexoleDopamine agonist+Pain, fatigueOffLimited population studied Pregabalin  2  binding: ↓neuronal excitation +++Pain, sleep, anxiety On SertralineSSRI++Pain, depressionOffCompared versus physical therapy TramadolOpioid agonist SNRI ++PainOff VenlafaxineSNRI > SSRI+Pain, depression, anxiety OffLimited FM study +++: strong evidence for use/efficacy; ++: moderate evidence use/efficacy; +: some evidence use/efficacy; -: no evidence for use/efficacy SSRI, selective serotonin reuptake inhibitor (alphabetical order)

152. Video 2

153. Video de-brief

154. Summary It is rare that treatment will result in full symptom remission Focus for therapy is to increase the level of function, accepting some degree of residual symptoms Educate patients around realistic treatment goals Where possible, quantify symptoms and level of function An interdisciplinary team can assist in education, establishing and reinforcing treatment goals For pharmacologic treatment: start low, go slow! Menu