Evolving Treatments for Patients with Fibromyalgia

Transcription

1 4:30pm - 5:30pm: Breakout 5 - Women s Health Option C: Evolving Treatments for Patients with Fibromyalgia ACPE UAN L01-P 0.1 CEU/1.0 Hr. Activity Type: Application-Based Program Objectives for Pharmacists: Upon completion of this program, participants should be able to: 1. Describe the pathophysiology of fibromyalgia and comorbidities associated with the condition. 2. Distinguish the pharmacologic treatment options for fibromyalgia including their mechanism of actions and potential side effects. 3. Recall the nonpharmacologic treatment options and lifestyle modifications recommended for patients with fibromyalgia. 4. Explain the value of a multidisciplinary approach for managing patients with fibromyalgia. Speaker: Geoffrey Wall, PharmD, FCCP, BCPS, CGP, is an Associate Professor, Department of Pharmacy Practice, College of Pharmacy at Drake University, and Clinical Assistant Professor, Department of Pharmacology and Physiology at Des Moines University, College of Osteopathic Medicine. His clinical practices include the Internal Medicine and Medical Intensive Care Teaching Services at Iowa Methodist Medical Center as well as the Inflammatory Bowel Disease Center in Des Moines, IA. Dr. Wall received his Bachelor of Science in Pharmacy from the University of Utah in 1992 and his Doctor of Pharmacy from Idaho State University in He completed an ASHP-accredited Internal Medicine Specialty Residency at Scott and White Memorial Hospitals and Clinics in He is Board-Certified in Pharmacotherapy and is a Certified Geriatric Pharmacist. He is a Fellow of the American College of Clinical Pharmacy. Dr. Wall has written a number of peer-reviewed papers and textbook chapters on a variety of topics, and has designed or participated in several clinical trials. His research interests include drug treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD), drug allergy and rheumatologic disorders. He has been selected for several teaching awards and was the Drake University Madelyn Levitt Mentor of the Year in He was also named Hospital Pharmacist of the Year by the Iowa Pharmacy Association in Speaker Disclosure: Geoffrey Wall reports he has no actual or potential conflicts of interest in relation to this program. The speaker has indicated that off-label use of medications will be discussed during this presentation.

2 2010 Educational Expo Evolving Treatments for Patients with Fibromyalgia Geoffrey C. Wall, PharmD, FCCP, BCPS, CGP Pre- & Post-Assessment Questions 1. Recent data suggests that FMS patients may make antibodies to which substance? a. Epinephrine b. Serotonin c. Dopamine d. Estrogen 2. A condition associated with FMS described as an attitude or behavior in which pain is characterized as always horrible and completely unbearable is termed: a. Munchausen's syndrome b. Malingering c. Catastrophizing d. Personality disorder 3. Which of the following gastrointestinal disorders is commonly found in patients with FMS? a. Irritable bowel syndrome b. Ulcerative colitis c. Peptic ulcer disease d. Gastroesophageal reflux disease 4. Which of the following statements are true concerning the role of exercise therapy in FMS? a. Aquatic exercise therapy may be particularly beneficial in FMS patients b. Pharmacotherapy is consistently superior in improving global functioning compared to exercise therapy c. Strength therapy is the preferred type of exercise for all FMS patients d. Exercise therapy should only be attempted if pharmacotherapy has failed 5. Which skeletal muscle relaxant has been used for years for FMS? a. Carisoprodol b. Cyclobenzaprine c. Meprobamate d. Baclofen

3 6. Which tri-cyclic antidepressant would be expected to have the least risk for anticholinergic effects in an FMS patient? a. Amitriptyline b. Nortriptyline c. Imipramine d. Amoxapine 7. Which of the following statements is true regarding the use of selective serotonin reuptake inhibitors (SSRIs) in FMS? a. SSRIs are the most effective drugs in the antidepressant class for treating FMS b. SSRIs have more modest effects in FMS compared to Tri-cyclic antidepressants c. SSRIs are not beneficial in FMS d. SSRIs are contraindicated for FMS due to worsening of symptoms 8. Patients with FMS who are started on duloxetine should be counseled about what rare but potentially serious adverse effect? a. Pulmonary fibrosis b. Renal toxicity c. Thyroid dysfunction d. Hepatotoxicity 9. Which of the following statements is true concerning milnacipran? a. It is approved in the U.S. for treatment of neuropathic pain and FMS b. It is approved in the U.S. for treatment of depression and FMS c. It is approved in the U.S. for treatment of panic disorder and FMS d. It is approved in the U.S. for FMS only 10. According to the American Pain Society guidelines what is the role of opioids in FMS? a. Moderate opioid-nonopioid combinations (such as hydrocodone/acetaminophen) are recommended for FMS pain b. Methadone is the drug of choice for FMS pain c. Opioids are the drugs of last choice for FMS pain d. Opioids should never be used for FMS pain due to lack of efficacy

4 Geoffrey C. Wall, Pharm.D., FCCP, BCPS, CGP Internal Medicine Clinical Pharmacist Iowa Methodist Medical Center Associate Professor of Pharmacy Practice Drake University College of Pharmacy and Health Sciences Objectives Describe the pathophysiology of fibromyalgia and comorbidities associated with the condition Distinguish the pharmacologic treatment options for fibromyalgia including their mechanism of actions and potential side effects Recall the nonpharmacologic treatment options and lifestyle modifications recommended for patients with fibromyalgia Explain the value of a multidisciplinary approach for managing patients with fibromyalgia Etiology/Epidemiology 2 3.5% of the U.S. population (six to ten million Americans) Characteristics Much more likely to be Caucasian female Often numerous co morbidities Young adult to middle age at onset Costs Three times higher than controls and reaches about $10,000/yearly for FMS claims alone Etiology/Epidemiology Cause of FMS has remained elusive Usually no precipitating trauma Genetic predisposition that leads to aberrant pain and sensory processing?? Primary sleep disorder?? Neurotransmitter abnormalities or antibodies?? Goldenberg DL. Rheum Dis Clin North Am. 2002; 28: Berger A, Int J Clin Pract. 2007;61: Arnold Lm, et al Arthritis Rheum 2004;50: Davies KA, et al Rheumatology 2008;47: Diagnosis Classic ACR criteria History of widespread pain has been present for at least three months Pain in both sides of the body Pain above and below the waist In addition, axial skeletal pain (cervical spine, anterior chest, thoracic spine or low back pain) must be present. Pain in 11 of 18 tender point sites on digital palpation Diagnosis Problems with ACR criteria Never intended for clinical use FMS is not a discrete disorder Spectrum of somatic and psychologic complaints Tender point count has very low specificity for FMS Bottom line: use ACR criteria as a guide not the final arbiter Wolf F, et al Arthritis Rheum 1990;33: Petzke F, et al J Rheumatol 2003;30:567 74

5 Co Morbidities With FMS Chronic Fatigue Syndrome Temporomandibular Disorder Irritable Bowel Syndrome Interstitial cystitis Post concussive syndrome Multiple chemical sensitivities Chronic tension type headache Chronic pelvic pain Chronic low back pain Is FMS a Functional Disorder? Many patients and clinicians believe this is a somatoform disorder Clinicians have been dismissive of FMS Obligation to treat this patients as any other Empathy during encounters with these patients is crucial to developing a trusting health care relationship Emerging data shows we are closer to developing objective criteria for diagnosis Catastrophizing Attitude or behavior in which pain is characterized as always horrible and completely unbearable Often with psychiatric co morbidities Can occur with any chronic non malignant pain VERY challenging patients Multi Disciplinary Approach to FMS Crucial to successful treatment and effective use of health care resources Physicians, nurses, pharmacists, therapists, psychologists, and others Patient education sessions are important for buy in and adherence Aim for increased sense of control of disease by patient Burton AK, et al. Spine 1995;20:722 8 Goldenberg DL J Clin Psychiatry. 2008;69 Suppl 2:30 4. New Guidelines European League Against Rheumatism (EULAR) First comprehensive evidenced based document on treatment of FMS Expert panel convened to review clinical data Emphasis on RCTs and Meta analyses Treatment Non pharmacologic EXERCISE** Cognitive behavioral therapy (CPT)* Relaxation therapy Physiotherapy Psychological support Aromatherapy **Strong evidence to support *Moderate evidence to support Carville SF, et al Ann Rheum Dis. 2008;67:536 41

6 Exercise Most studied intervention in FMS Aerobic vs Strength training vs heated pool (aquatic) Recent meta analysis found benefit in all types, with possible highest benefit in aquatic therapy Improves fatigue, sleep, pain, perhaps cognition! CPT Psychotherapy that emphasizes techniques toward imparting coping skills for emotional dysfunction and negative thinking Few adverse effects, but is time consuming and may be expensive Studies demonstrate modest improvements in pain and physical functioning Most important benefit is catastrophizing risk reduction Busch AJ, et al J Rheumatol 2008;35: Bennett R, et al. Nature Clinical Practice Rheumatology 2006;2: Pharmacotherapy for FMS Can be utilized in all phases of disease Combining medication with non pharmacologic therapy is crucial AVOID Opioid analgesics (last line therapy) Non steroidal Anti Inflammatories Corticosteroids Pitfalls in examining evidence for medications in FMS Small studies with poor methodology Short time frames High placebo rate Up to 50% in some studies Outcomes Pain (VAS), general health surveys Fibromyalgia Impact Questionnaire (FIQ) General EULAR Guidelines 1. Tramadol is recommended for management of pain from FMS 2. Antidepressants are recommended to decrease pain and improve function 3. Tropisetron, pramipexole, and pregabalin are recommended to reduce pain of FMS. Skeletal Muscle Relaxants (SMRs) Among oldest therapies for FMS Cyclobenzaprine most studied Works primarily by restoring normal sleep patterns Meta analysis data found moderate effect on functioning 0.21 (95% CI )), less benefit in pain MUST titrate slowly to avoid anticholinergic adverse effects (e.g. start at 5mg qhs) Tofferi JK, et al Arthritis Rheum. 2004;51:9 13

7 Tri Cyclic Antidepressants 5 HT and NE reuptake blockers with long history of use in FMS Modulation of Neuropathic pain and restoring normal sleep patterns Meta analysis data found improvements in sleep, pain functioning but benefits lost at 8 weeks Slow titration needed to avoid ADRs Would favor use of secondary TCAs desipramine and nortriptyline over amitriptyline Nishishinya B, et al Rheumatology 2008;47: Selective serotonin reuptake inhibitors (SSRIs) Nearly all have been studied in FMS Most studies have demonstrated modest benefits in pain and physical functioning especially compared to TCAs WHY?? Is NE levels key to pain modulation in FMS? ADRs: Nausea, sexual dysfunction, EPS, hyponatremia, CNS disturbances Häuser W, et al JAMA. 2009;301: Duloxetine Balanced 5 HT and NE reuptake inhibitor Indicated for several neuropathic pain syndromes, depression and FMS Second drug to receive indication for FMS ADRs: Dry mouth, nausea, somnolence, and constipation Liver toxicity reported Duloxetine Efficacy Recent systematic review Three published trials were examined Primary efficacy outcome was at least 50% pain relief per patient report A moderate area effect was found in FMS patients (SMD % CI ( ), NNT about 5) Dosing Start at 30mg daily and increase in one week to 60 mg daily Sultan A, et al. BMC Neurology 2008;8: /8/29. Accessed 3/27/09 Milnacipran Balanced 5 HT and NE reuptake inhibitor Newest agent to be approved in U.S. for FMS (NOT approved for depression) ADRs: Nausea, headache, constipation, dizziness, insomnia, hot flush, and increase in blood pressure Milnacipran 15 week, MC, R, DB, PC study of 1200 patients Dose ranging study: milnacipran 100mg daily, 200mg daily or placebo Primary outcomes: total symptom responders and pain responders (>30% decrease in pain scores) Clauw DJ, et al Clin Therapeutics 2008;30:

8 Results mg 200mg Placebo Analgesics Several agents examined mostly in underpowered, methodologically flawed trials Three agents with stronger evidence: Gabapentin Pregabalin* Tramadol 0 Primary Pain Outcome Both active arms p < 0.01 vs placebo * = FDA approved Gabapentin Structural analog of γ Aminobutyric acid (GABA) with analgesic effects in neuropathic pain Investigated in FMS with a R, DB, PC, MC study 12 week study with 150 patients treated with gabapentin titrated to a median dose of 1800mg daily or placebo Primary outcome: a >30% improvement in pain, FIQ Results Gabapentin Placebo 0 > 30% Pain Improvement Arnold LM, et al Arthritis and Rheumatism 2007;56: p = Pregabalin Derivative of gabapentin with narrower dosage range Approved largely on basis of FREEDOM trial 6 month study with pregabalin titrated to 600mg (based on pain relief and tolerability) vs placebo Patients improved on pregabalin looking at sustainability of effect Results Pregabalin Placebo 0 Loss of Response p < 0.001

9 Gabapentin and Pregabalin ADRs Dizziness, ataxia, drowsiness, and peripheral edema Both drugs are excreted mostly unchanged in the urine Need to reduce dose for acute changes in renal function Tramadol Effects on central serotonin and norepinephrine reuptake inhibition as well as mu opioid receptors Specifically recommended by EULAR guidelines for pain in FMS DOES CAUSE opioid ADRs Lowers seizure threshold Must reduce dose with renal impairment Pramipexole Dopamine agonist found in one small study to be beneficial for FMS pain Recommended by EULAR High doses studied: 4.5mg/daily Numerous ADRs Anxiety, orthostasis, dizziness, hallucination, sudden sleep episodes, compulsive behaviors Expensive Reserve as last line agent Holman AJ, et al Arthritis Rheum ;52: Complimentary & Alternative Medicine (CAM) Includes Clinical hypnosis, biofeedback, acupuncture, chiropractic manipulation, myofascial release therapy, therapeutic massage Neutraceuticals/Herbal medications Used commonly by FMS patients Often not discussed with treating physician Wall GC, et al Pharmacy Practice 2007;5: Well, we really don t know how effective or safe these agents are, and we don t often have confidence in the quality control of many herbal products What to do? Look at existing clinical data: For example a well done sham controlled study did NOT find benefit with acupuncture in FMS Where efficacy data is lacking look at safety vs giving patient a measure of control over their disease (and costs) Turk DC, et al. J Pain 2008;9: Assefi NP, et al.. Ann Intern Med. 2005;143:10 9.

10 Neutraceuticals/Herbals Magnesium, S adenosylmethionine [SAMe], high dose dextramethophoran, guaifenesin, and 5 hydroxytryptophan (5 HTP) To date only strong data showing benefit with magnesium and SAMe Avoid The Medicine Show Neutraceuticals/Herbals Magnesium/malic acid (50 mg/200mg three times a day) Small study (n = 24) showed improvement in pain scores Benefit lost at 4 weeks ADRs not reported Russell IJ, et al J Rheumatol. 1995;22:953 8 Neutraceuticals/Herbals SAMe 800mg daily Endogenous hormone needed for proper neurotransmitter function Largest study (n = 44) found significant improvements in pain, fatigue, morning stiffness, and mood Possible ADRs: nausea, dry mouth, dizziness and diarrhea Jacobsen S, et al Scand J Rheumatol. 1991;20: Treatment Approach to FMS Exercise therapy +/ CBT are cornerstones of therapy Discuss existing treatments with patient to help insure compliance First Line: Cyclobenzaprine/TCAs Second Line: Switch to Pregabalin or Duloxetine Third Line: Switch to milnacipran or Tramadol Therapeutic trials of each until a effective/tolerated therapy found Conclusion FMS impacts multiple aspects of a patient's life and requires a multidisciplinary approach for successful management Clinicians role: Education of appropriate therapies, managing adverse effects and containing costs Newly approved therapies give patients more options than ever for this disorder Geoffrey C. Wall, Pharm.D Geoff.wall@drake.edu

11 2010 Educational Expo Evolving Treatments for Patients with Fibromyalgia Geoffrey C. Wall, PharmD, FCCP, BCPS, CGP Pre- & Post-Assessment Answers 1. Recent data suggests that FMS patients may make antibodies to which substance? a. Epinephrine b. Serotonin c. Dopamine d. Estrogen 2. A condition associated with FMS described as an attitude or behavior in which pain is characterized as always horrible and completely unbearable is termed: a. Munchausen's syndrome b. Malingering c. Catastrophizing d. Personality disorder 3. Which of the following gastrointestinal disorders is commonly found in patients with FMS? a. Irritable bowel syndrome b. Ulcerative colitis c. Peptic ulcer disease d. Gastroesophageal reflux disease 4. Which of the following statements are true concerning the role of exercise therapy in FMS? a. Aquatic exercise therapy may be particularly beneficial in FMS patients b. Pharmacotherapy is consistently superior in improving global functioning compared to exercise therapy c. Strength therapy is the preferred type of exercise for all FMS patients d. Exercise therapy should only be attempted if pharmacotherapy has failed 5. Which skeletal muscle relaxant has been used for years for FMS? a. Carisoprodol b. Cyclobenzaprine c. Meprobamate d. Baclofen

12 6. Which tri-cyclic antidepressant would be expected to have the least risk for anticholinergic effects in an FMS patient? a. Amitriptyline b. Nortriptyline c. Imipramine d. Amoxapine 7. Which of the following statements is true regarding the use of selective serotonin reuptake inhibitors (SSRIs) in FMS? a. SSRIs are the most effective drugs in the antidepressant class for treating FMS b. SSRIs have more modest effects in FMS compared to Tri-cyclic antidepressants c. SSRIs are not beneficial in FMS d. SSRIs are contraindicated for FMS due to worsening of symptoms 8. Patients with FMS who are started on duloxetine should be counseled about what rare but potentially serious adverse effect? a. Pulmonary fibrosis b. Renal toxicity c. Thyroid dysfunction d. Hepatotoxicity 9. Which of the following statements is true concerning milnacipran? a. It is approved in the U.S. for treatment of neuropathic pain and FMS b. It is approved in the U.S. for treatment of depression and FMS c. It is approved in the U.S. for treatment of panic disorder and FMS d. It is approved in the U.S. for FMS only 10. According to the American Pain Society guidelines what is the role of opioids in FMS? a. Moderate opioid-nonopioid combinations (such as hydrocodone/acetaminophen) are recommended for FMS pain b. Methadone is the drug of choice for FMS pain c. Opioids are the drugs of last choice for FMS pain d. Opioids should never be used for FMS pain due to lack of efficacy