Oh My Aching Body Understanding Fibromyalgia

Transcription

1 Page 1 Oh, My Aching Body: Understanding Fibromyalgia Geneva Clark Briggs, PharmD, BCPS This program has been brought to you by PharmCon Oh, My Aching Body: Understanding Fibromyalgia Accreditation: Pharmacists: L01-P Pharmacy Technicians: L01-T Nurses: N-638 CE Credits: 1.0 contact hour Target Audience: Pharmacists, Technicians & Nurses Program Overview: This program reviews the updated diagnostic criteria for fibromyalgia and the current postulated pathophysiology leading to increased pain perception. The evidence for various prescription and nonprescription therapies for treating this difficult disease will be discussed. The program includes information on pharmacologic treatments, patient counseling, and a question and answer period. PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Objectives: Summarize the issues with pain perception in fibromyalgia Review the efficacy of prescription agents for managing fibromyalgia Recommend nonprescription alternatives for managing fibromyalgia in appropriate patients This program has been brought to you by PharmCon Oh, My Aching Body: Understanding Fibromyalgia Speaker: Dr. Geneva Clark Briggs, a board-certified Pharmacotherapy Specialist, received her Doctor of Pharmacy and Bachelor of Science in Pharmacy degrees from Virginia Commonwealth University, Medical College of Virginia. Dr. Briggs is a clinical associate with MedOutcomes, Inc, where she develops and presents educational programs for pharmacists. Speaker Disclosure: Dr. Briggs has no actual or potential conflicts of interest in relation to this program This program has been brought to you by PharmCon PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Outline What is fibromyalgia and how do you know if someone has it? What is thought to cause fibromyalgia related pain? How is it treated? Nonpharmacologic Prescription therapies Alternative medications

2 Page 2 Clinical Features of FM WIDESPREAD PAIN Chronic, widespread pain is the defining feature of FM Patient descriptors of pain include: aching, exhausting, nagging, and hurting TENDERNESS Presence of tender points Most patients also have tenderness to pressure, heat, cold, electrical pain SLEEP DISTURBANCES Characterized by nonrestorative sleep and increased awakenings Abnormalities in the continuity of sleep and sleep architecture Reduced slow-wave sleep Abnormal alpha wave intrusion in non- REM sleep FATIGUE/STIFFNESS Morning stiffness and fatigue are common characteristics of FM Overlap Between Fibromyalgia and Related Syndromes Fibromyalgia 2-6% of population Defined by widespread pain and tenderness Regional Pain Syndromes Irritable Bowel Painful bladder/ interstitial cystitis Tempromandibular Disorder Tension headache Vulvodynia Pain and/or sensory amplification Arthritis Rheum. 1995;38:19-28; Arthritis Rheum. 1990:33: ; Arthritis Rheum. 2001;44: ; Am J Med Sci. 1998;315: Clauw DJ, et al. Neuroimmunomodulation. 1997;4: Chronic Fatigue Syndrome (CFS) 1% of population Fatigue and 4 of 8 minor criteria Psychiatric Disorders Major depression OCD Bipolar PTSD Generalized anxiety disorder Panic attack Somatoform Disorders 4% of population Multiple unexplained symptoms no organic findings Medical Disorder 1 Medical and Psychiatric Comorbidities with FM Prevalence (%) Chronic fatigue syndrome IBS TMD 75 Tension and migraine headache Multiple chemical sensitivities Interstitial cystitis Chronic pelvic pain 18 Psychiatric Disorder 2 OCD=obsessive-compulsive disorder. PTSD=posttraumatic stress disorder. 1. Best Pract Res Clin Rheumatol. 2003;17: J Clin Psychiatry. 2006;67: Lifetime Prevalence (%) Major mood disorder 73.1 Major depressive disorder 62.0 Bipolar disorder 11.1 Anxiety disorder 55.6 Panic disorder 28.7 PTSD 21.3 Social phobia 19.4 OCD 6.5 Interactive Question What percentage of FM patients are women? a % b % c %

3 Page 3 Who Gets Fibromyalgia? 2-6% of population 4-6 times > diagnosis in females All ages but peak Some ethnic groups may have higher risk but conflicting data Fibromyalgia ACR Diagnostic Criteria History of widespread pain ( 3 months) Above and below the waist Bilaterally In the axial skeleton Pain in 11 of 18 specific fibromyalgia tender points on digital palpation Palpation force: 4 kg/1.4 cm 2 Approximately pressure required to blanche the fingernail of the examiner Pain. 2006;124: , Lupus. 1998;7: , Lupus. 2003;12: , Arthritis Rheum. 1995;38:19-28., Ethn Dis. 2008;18: , Pain Med. 2003;4: , J Palliat Med. 2006;9: J Rheumatol. 1997;24: , Arthritis Rheum. 1990;33: Issues with Tender Point Count The threshold of 11/18 tender points may be too insensitive Most clinicians don t use TPC for diagnosis Many don t do it correctly FM diagnostic criteria should reflect better understanding of pathophysiology in FM ACR Preliminary Diagnostic Criteria for Fibromyalgia 1. Pain & symptoms present for 3 months or longer 2. Widespread pain index (WPI, 0-19) 3. Symptom severity scale (SS, 0-12) Fatigue Waking unrefreshed Cognitive symptoms Somatic symptoms Pain 3 mo + WPI > 7 & SS >5 OR WPI 3-6 & SS > 9 Arthritis Care Res. 2010; 62:

4 Page 4 Pathogenesis of FM and Related Conditions Genetics Triggers Mechanisms Relationship between physiological and psychological factors Disordered sensory processing Autonomic/neuroendocrine dysfunction Arch Intern Med. 1999;159(8): Best Pract Res Clin Rheumatol. 2003;17(4): Ann Intern Med. 2007;146(10): Genetic Factors in FM 5-HT2A receptor polymorphism T/T phenotype Serotonin transporter COMT (catecholamine o-methyl transferase) Arthritis Rheum. 2004;50(3): Hum Mol Genet. 2005;14(1): Neurobiol Dis 1999;6:433-9 Arthritis Rheum. 1999;42: Rheumatol Int. 2003;23:104-7 >8 Odds Ratio for First-Degree Relatives to Develop Fibromyalgia Stressors Capable of Triggering FM and Related Illnesses Peripheral pain syndromes Infections (eg,parvovirus, Lyme disease, Q fever, hepatitis) Physical trauma (automobile accidents) Psychological stress/distress Hormonal alterations (eg, hypothyroidism) Certain catastrophic events (war, but not natural disasters) Fibromyalgia Pathophysiology: The Role of Plasticity in Chronic Pain Normal Healing Pain Relief Injury Acute Pain Hyperalgesia Healing With Plasticity Chronic Pain Allodynia Neuroimmunomodulation. 1997;4(3): Med Hypotheses. 2004;63(4): Marcus DM. Am Fam Physician. 2000;61:

5 Pain Intensity Page 5 Central Sensitization in Chronic Pain Enhanced Pain Processing fmri findings Tissue Damage PERIPHERAL ACTIVITY Nerve Damage Hyperalgesia Decreased threshold to peripheral stimuli Spontaneous Pain CENTRAL SENSITIZATION Allodynia Increased Expansion of Spontaneous Receptive field activity Comparison of 16 FM Patients vs 16 Healthy Controls fmri=functional magnetic resonance imaging. Arthritis Rheum. 2002;46(5): Fibromyalgia Subjective pain control Stimulus Intensity, kg/cm 2 Similar pressure produced significantly greater activation at 13 regions in the patient group and 1 region in the control group Stimulus pressure control 4.5 Fibromyalgia Pathophysiology Fibromyalgia Pathophysiology Ascending pathways Descending Modulation Descending modulatory pathways Facilitation Substance P Glutamate and EAAs NGF Inhibition Descending antinociceptive pathways Norepinephrine and serotonin (5-HT 1a,b ) Opioids Mechanism Central sensitization Abnormalities of descending inhibitory pain pathways Neurotransmitter abnormalities Comorbid psychiatric conditions Description Amplification of pain in the spinal cord via spontaneous nerve activity, expanded receptive fields, and augmented stimulus responses Dysfunction in brain centers (or the pathways from these centers) that normally downregulate pain signaling in the spinal cord Decreased serotonin and norepinephrine in the CNS leading to aberrant pain signaling Decreased dopamine transmission in the brain leading to chronic pain via unclear mechanisms Depression, anxiety, PTSD, and somatization, which may predispose individuals to the development of fibromyalgia 5-HT=serotonin. EAA=excitatory amino acid. NGF=nerve growth factor. J Neurosci. 2007;27: ; Prog Neurobiol. 2002;66: ; Arthritis Rheum. 1992;35: ; Arthritis Rheum. 1994;37: ; Pain. 2007;8: CNS, central nervous system; PTSD, post-traumatic stress disorder. Ann Intern Med. 2007;146:

6 Page 6 From Mechanism to Treatment Dually Focused Treatment Primarily a neural disease and central sensitization plays a critical role (neuropathic pain) Deficiency of noradrenergicserotonergic activity and/or excess levels of excitatory neurotransmitters Lack of sleep or exercise increase pain and other somatic symptoms Treatments aimed at the periphery (ie, topicals, injections) are not very efficacious Subgroups of patients with FM need different treatments Drugs to target these neurotransmitters Exercise, sleep hygiene, and other behavioral interventions are effective therapies for biological reasons Symptoms of pain, fatigue, etc Nociceptive processes Neuroendocrine and sleep dysfunction Disordered sensory processing Functional consequences of symptoms Increased distress Decreased activity Isolation Poor sleep Maladaptive illness behaviors Thoughts affect pain levels Cognitive therapies are effective in FM and have a Arch Intern Med. 1999;159: biological substrate Best Pract Res Clin Rheumatol. 2003;17: Ann Intern Med. 2007;146: Best Pract Res Clin Rheumatol. 2003;17: Pharmacologic therapies to improve symptoms Nonpharmacologic therapies to address dysfunction Nonpharmacological Therapies Poll Question Strong Evidence Education Aerobic exercise Cognitive-behavioral therapy (CBT) Modest Evidence Strength training Hypnotherapy Balneotherapy Weak Evidence Chiropractic, manual, and massage therapy Acupuncture, electrotherapy, ultrasound Meditation Biofeedback Yoga No Evidence Tender-point injections (TPIs), flexibility exercise Which is the most important treatment of fibromyalgia? a. Medications b. Exercise c. Psychotherapy d. Patient education JAMA. 2004;292: Clin Exp Rheumatol. 2009;27(5 Suppl 56):S29-32, S46-50.

7 Page 7 Patient Education The Most Important Treatment for FM Validate pain Explain disease Realistic expectations Goal is not to be pain free but to have reduced/manageable pain Patient responsibilities J Rheumatol. 1994;21: Patient Educ Couns. 2002;48: Am J Phys Med Rehabil. 2003;82: Arch Intern Med. 2007;167: Exercise Aerobic exercise is nearly universally beneficial Tolerance & adherence are biggest issues To maximize benefits Begin gradually after pharmacologic therapy Begin with stretching, low-impact exercises; avoid strength training until later Goal is to achieve regular, consistent physical activity Cognitive Behavioral Therapy (CBT) A program designed to teach patients techniques to Reduce their symptoms Increase coping strategies Identify and eliminate maladaptive illness behaviors Shown to be effective for nearly any chronic medical illness Pharmacologic Approaches

8 Page 8 Pharmacologic Management of Neuropathic Pain Pharmacological Therapies in FM Central Sensitization Calcium Channels - Gabapentin, pregabalin, lamotrigine J Pain Symp Management Peripheral Sensitization Sodium Channels - TCAs, carbamazepine, oxcarbamazepine, phenytoin, lamotrigine, lidocaine, mexiletine Strong Evidence No Evidence Dual reuptake inhibitors Opioids Tricyclic compounds Corticosteroids (amitriptyline, cyclobenzaprine) NSAIDs SNRIs (milnacipran, duloxetine) Benzodiazepine and Pregabalin nonbenzodiazepine Modest Evidence hypnotics Tramadol Guaifenesin Gabapentin Venlafaxine SSRIs Gamma-hydroxybutyrate Dopamine agonists SNRI=serotonin norepinephrine reuptake inhibitor. SSRI=selective serotonin reuptake inhibitor. JAMA. 2004;292: , Ann Rheum Dis. 2008;67(4): , J Rheumatol. 2003;30(5): , Curr Opin Rheumatol. 2008;20(3): Arthritis Rheum. 2007;56(4): Pain Medication Usage Patterns in FM Relative Activity on Serotonin and Norepinephrine Reuptake Serotonin Mixed Norepinephrine Citalopram Fluvoxamine Sertraline Paroxetine Venlafaxine Amitriptyline Duloxetine Milnacipran Cyclobenzaprine Imipramine Maprotiline Desipramine Nortriptyline Fluoxetine P<.001. COX=cyclo-oxygenase. NSAID=nonsteroidal anti-inflammatory drug. Int J Clin Pract. 2007;61(9): Antidepressant Pain Med. 2000;1(4): Analgesic Antidepressant Best evidence of efficacy in FM

9 Pain Reduction % of Patients With Pain Relief Page 9 Duloxetine (Cymbalta ) Pain Relief in Patients With FM FDA-approved for FM An SNRI Dosage should be titrated until recommended dose of 60 mg/day is achieved Common side effects: nausea, headache, dry mouth, dizziness, somnolence, constipation, and fatigue Pain. 2008;136(3): Pain. 2005;119(1-3): Duloxetine 60 mg/day Placebo n=260 n=257 Milnacipran (Savella ) Mean Change in Pain Over Time FDA-approved for FM An SNRI, though its norepinephrine reuptake inhibition predominates Dosage needs to be titrated to recommended dose 100 mg/day (50 mg twice daily) Side effects: nausea, constipation, hot flush, hyperhidrosis, vomiting, palpitations, dry mouth, and hypertension Week J Rheumatol. 2005;32:

10 Page 10 Pregabalin (Lyrica ) First FDA-approved medication for FM Binds to the alpha2-delta ( 2 ) site of voltage-gated calcium channels in the CNS Dosage needs to be titrated, until recommended dose of mg/day is achieved Side effects: dizziness, somnolence, headache, dry mouth, constipation, blurred vision, weight gain, and difficulty with concentration/attention Comparing the 3 Approved Agents Meta-analysis of 11 trials (>6,000 pts) All reduce pain ~20-30% Duloxetine & pregabalin > milnacipran in reducing pain and sleep disturbances Duloxetine > milnacipran & pregabalin in reducing depressed mood Milnacipran & pregabalin > duloxetine in reducing fatigue J. Pain 2010:11; Gabapentin (Neurontin ) Indicated for post-herpetic neuralgia Binds to the alpha2-delta ( 2 ) site of voltage-gated calcium channels in the CNS 51% of 75 FM subjects had 30% reduction in pain Titrate dose to 1,200-2,400 mg/day Side effects: dizziness, somnolence, and peripheral edema Arthritis Rheum. 2007;56: Tramadol Dual action Mild opioid action plus mild serotonin and norepinephrine action Modest evidence of efficacy Side effects: nausea, dizziness, somnolence, constipation Reports of Classic opioid withdrawal with sudden discontinuation Abuse and dependency potential Arthritis Rheum. 2005;53: Pain Pract. 2009;9: Ther Clin Risk Manag. 2007;3:

11 Page 11 Pramipexole (Mirapex ) Dopamine receptor agonist Modest evidence of efficacy Placebo-controlled study 82% improved pain 42% had a >50% decrease in pain when taken in addition to other medications Also improved: fatigue and function Dosing: start with mg every night, gradual increase up to 4.5 mg every night 33% prevalence of RLS in FM Arthritis Rheum. 2005;52: J Clin Sleep Med. 2010;6: Poll Question Agents which decrease peripheral sensitization are effective in treating fibromyalgia a. True b. False Agents to Reduce Peripheral Nociceptive Input Medicine Class Topical analgesics Muscle relaxers Capsaicin Trigger point injections Botulinum toxin type A NSAIDs, COX-2 inhibitors Little or No Evidence of Benefit in FM Case Presentation AJ is a 47 year old female with a 4 year history of FM Currently being treated with pregabalin and milnacipran Practices good sleep hygiene and walks 20 mins 3 x/week Prior treatments: CBT, acupuncture, TENS Still having moderate pain and significant fatigue Asks Are there any supplements that might help me?

12 Page 12 Supplements & Alternative Medications for FM 43% in one phone survey took at least one Most common were omega fatty acids, glucosamine, gingko In a FM clinic: 35% used vitamin C, 31% vitamin E, 29% magnesium, 25% vitamin B complex, 24% green tea J Womens Health. 2009;18: , J Altern Complement Med. 2010;16: J Int Med Res. 2002;30: Mayo Clin Proc. 2005;80: Intravenous micronutrient therapy (IVMT, Myer s Cocktail) 1 randomized, placebo controlled trial (n=31) Once a week infusion for 8 weeks Significant placebo effect, greater but not statistically significant effect of IVMT J Altern Complement Med. 2009;15: Alternative Medications Chinese herbal medicine Anthocyanidins S-adenosylmethionine (SAMe) 400 mg bid diarrhea, dyspepsia, anxiety, headache, mania, insomnia, allergy, and rashes serotonin J Altern Complement Med. 2010;16: J Nutr Environ Med 2000;10: Scand J Rheumatol 1991;20: Alternative Medicines Homeopathy Rhus toxicodendron (6c potency) tid Arnica montana, Bryonia alba and R. toxicodendron (all of 6c potency) Adverse effects: allergic reactions, photodermatitis Clin Rheumatol. 2010;29: Br Med J 1989;299: Br Homeopath J 1986;75: Rheumatology 2004;43:

13 Page 13 Case 47 year on pregabalin and milnacipran Would an alternative medicine be beneficial? Which one would you suggest to her? Overall Management of FM Educate the patient Multidisciplinary and combination therapy approach Pharmacologic and nonpharmacologic therapies Target medications to underlying pathophysiology Individualized treatment goals Successful outcome does not mean painfree Notes Notes