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Fibromyalgia Information Foundation Fall Conference 2008

Fibromyalgia Information Foundation Fall Conference 2008. F I F. www.myalgia.com. New developments in fibromyalgia research and treatment. Robert Bennett MD, FRCP, FACP, MACR. F I F. Some of the FM drug studies that are underway or completed. COMPLETED STUDIES Duloxetine Milnacipran

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Fibromyalgia Information Foundation Fall Conference 2008

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  1. Fibromyalgia Information Foundation Fall Conference 2008 F I F www.myalgia.com

  2. New developments in fibromyalgia research and treatment Robert Bennett MD, FRCP, FACP, MACR F I F

  3. Some of the FM drug studies that are underway or completed COMPLETED STUDIES Duloxetine Milnacipran Desvenlafaxine Pregabalin * Gabapentin D-ribose MK-677 * Ropinirole Pyridostigmine * Pramipexole * Hydrocortisone * Levitiracetam Lacosamide Casopitant ACTIVE STUDIES Ultracet * Eszoplicone Calcitonin Reboxetine * Quetiapine Xyrem * Etoricoxib Rotigitone * Armodafinil Nabilone Neurotropin Fluoxetine Naltrexone Amitryptiline

  4. Two drugs currently FDA approved for fibromyalgia 1. June 21, 2007 - Lyrica (pregabalin) FDA approved indications: Partial onset seizures Post herpetic neuralgia Fibromyalgia 2. June 16, 2008 - Cymbalta (duloxetine) FDA approved indications: Depression Diabetic neuropathy Generalized anxiety disorder Fibromyalgia

  5. Pregabalin - Improvement in weekly mean pain scores Change from baseline in LS mean pain score Treatment Week Arnold et al. EULAR 2007, Barcelona, Spain, 13-16 June 2007.

  6. Pregabalin - Improvement in weekly mean pain scores Placebo response Change from baseline in LS mean pain score Treatment Week Arnold et al. EULAR 2007, Barcelona, Spain, 13-16 June 2007.

  7. Pregabalin Adverse Events Nocebo response *Due to all-cause AEs Arnold et al. EULAR 2007, Barcelona, Spain, 13-16 June 2007. 7

  8. Placebo Duloxetine 60 mg bid † † † † * * † † † † † † † † Duloxetine - Improvement in weekly mean pain scores 0.0 Duloxetine 60 mg qd -0.5 -1.0 -1.5 Change from baseline in LS mean pain score -2.0 -2.5 -3.0 -3.5 0 2 4 6 8 10 12 Week Arnold LM et al. (2005), Pain 119(1-3):5-15

  9. † † † † * * † † † † † † † † Duloxetine - Improvement in weekly mean pain scores 0.0 -0.5 Placebo response -1.0 -1.5 Change from baseline in LS mean pain score -2.0 -2.5 -3.0 -3.5 0 2 4 6 8 10 12 Week Arnold LM et al. (2005), Pain 119(1-3):5-15

  10. Duloxetine: Adverse Events † 45 Nocebo response † 40 Placebo (N=120) 35 Duloxetine 60 mg qd (N=118) 30 % of Patients Duloxetine 60 mg bid (N=116) * 25 * 20 † * * 15 * † * 10 * * * * * * 5 0 Nausea Diarrhea Anorexia Dry Mouth Somnolence Constipation Nervousness Hyperhidrosis Feeling Jittery Nasopharyngitis Decreased Appetite Arnold LM et al. (2005), Pain 119(1-3):5-15

  11. Are the placeobo and nocebo response for real? Yes they are for real

  12. Anatomy of pain 3. Brain 4. Descending modulation 1. Peripheral tissues 2. Spinal cord

  13. What treatments do FM patients really use?

  14. NFA internet survey 2005 - Interventions Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

  15. NFA internet survey 2005 - Interventions Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

  16. NFA internet survey 2005 – Analgesic use The most helpful drugs were all “opioids” Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

  17. PET Scanning The Journal of Neuroscience, September 12, 2007 • 27(37):10000 –10006 Neurobiology of Disease Decreased Central-Opioid Receptor Availability in Fibromyalgia Richard E. Harris, Daniel J. Clauw, David J. Scott, Samuel A. McLean, Richard H. Gracely, and Jon-Kar Zubieta

  18. μ-Opioid receptor availability in fibromyalgia Finding: About 1/3 of FM patients have nearly maximal occupation of opioid receptors N. acumbens L. amygdala R. ant. cingulate Harris et al. The Journal of Neuroscience 27(37):10000 –10006

  19. What does this stuff really mean? FINDING: Some FM patients have more endorphins than healthy individuals and their endorphin receptors are full CONSEQUENCE: These same patients will be relatively resistant to medications containing opioids

  20. Why do doctors prescribe antidepressants, even when you’re not depressed?

  21. Linking depression and pain Depression is associated with low brain levels of monoamines Serotonin, nor-epinephrine and dopamine

  22. Linking depression and pain Prefrontal cortex Limbic system Amygdala Hippocampus Hypothalamus Nor-epinephrine:Locus coeruleus Serotonin:Raphe nucleus Sleep center Spinal cord

  23. Reduced serotonin / norepinephrine Linking depression and pain Depressed Mood Poor Concentration Loss of AppetiteLow Sex DriveLoss of Pleasure Psychomotor Retardationand Agitation InsomniaHypersomnia Increased pain susceptibility

  24. Anatomy of pain 3. Brain 4. Descending modulation 1. Peripheral tissues 2. Spinal cord

  25. N Engl J Med 2005;352:1112-20. The serotonin syndrome is an adverse drug reaction that results from therapeutic drug use or inadvertent interactions between drugs

  26. Serotonin syndrome Cause: excessive stimulation of serotonin receptors Presentation: Agitation or restlessness Nausea, vomiting and diarrhea Confusion , hallucinations Poor coordination Tachycardia Rapid changes in blood pressure Sweating Hyper-reactive reflexes Fever Seizures Coma

  27. Serotonin syndrome – implicated drugs In some patients combinations of the following drugs can lead to a serotonin syndrome: SSRIs: citalopram (Celexa), fluoxetine (Prozac) SNRIs: duloxetine (Cymbalta), venlafaxine (Effexor) NDRIs: buproprion (Wellbutrin) MAOIs: isocarboxazid (Marplan) and phenelzine (Nardil) Analgesics: tramadol (Ultram), fentanyl (Sublimaze) Anti-migraine: sumatriptan (Imitrex) and zolmitriptan (Zomig) Anti-nausea: metoclopramide (Reglan) and ondansetron (Zofran) Bipolar:lithium (Lithobid) Cough: dextromethorphan (Robitussin DM) Herbal supplements: St. John's wort and ginseng This risk depends on genetic make-up (CYP 450 genes)

  28. What you have always wanted to know about Cytochrome P450 18 families and 43 variants Nomenclature: CYP1A1, CYP2D6, CYP3A4, etc. Function: drug metabolism Relevance: drug interactions Variants are genetically determined About 10% of Caucasians have low CYP2D6 activity

  29. Individualize drug dosing based on metabolic profiling of CYP variants 2005 - The FDA-approved AmpliChip for analysis of CYP2D6 and CYP2C19, variants of CYP450 1. Extensive metabolizers. Can be administered drug in "standard“ dosages2. Intermediate metabolizers. Multiple drug therapy can turn in people into poor metabolizers. 3. Poor metabolizers. May develop drug accumulation and adverse reactions 4. Ultrarapid metabolizers. May experience either no effect or less-than-expected effectiveness from their drug therapy

  30. You don’t have to wait 5 years Learn about fibromyalgia and help fellow sufferers Adopt a positive attitude, newer treatments are on the way Maintain a regimen of gentle stretching and exercise Learn to be kind to your body Maximize your “sleep hygiene” Give medications a chance (many need 3-4 weeks to work)

  31. The “New Normal”: Thriving in the here and now! Rebecca Ross RN, PhD Psychiatric Mental Health Nurse Practitioner F I F

  32. Identifying YOUR “New Normal” • Fibromyalgia-related changes occur in many spheres of life: • Physical Ability, • Energy Level, • Cognitive Ability, • Social Function, • Financial Stability, • Role Expectations (spouse, parent, employee, etc). “If you cry because the sun has gone out of your life, your tears will prevent you from seeing the stars.” -William Shakespeare

  33. Accepting “The New Normal” “The secret of health for both mind and body is not to mourn for the past, worry about the future or anticipate troubles, but to live in the present moment wisely and earnestly.” -- Buddha How to shift “paradigms”: • Identifying negative thoughts/beliefs about your health. • Challenging those thoughts/beliefs. • Adapting thought patterns and behaviors to more effective ways of thinking / behaving.

  34. Mastering “The New Normal” Tasks to Master: • Setting realistic expectations for self and others. • Learning to set healthy boundaries for self and others. • Learning to communicate with difficult friends & family (and acquaintances who think they are “helping”). • Finding and using resources that will help in the journey ahead.

  35. Mastering “The New Normal”: Realistic Expectations • Set realistic expectations with self: • Let go of what you use to be able to do. • Set priorities- Self, family, exercise, friends, work, etc. • Educate family/friends about current energy limits. • Enlist them is helping you set realistic goals. • Set realistic expectations with others: • You can not be the “fixer” for everyone. • Discuss priorities with important people and ask them to help with communicating their expectations. • Sometimes, you have to JUST SAY NO!

  36. Mastering “The New Normal”: Setting Healthy Boundaries • Energy: 100 units of energy for a 1000 unit day! • Break tasks down. Complete over a few days if necessary. • Six 15-minute blocks of time, which limits ante-grade pain, is better than an hour at a time and pain for the next two days. • Ask for help AND THEN LET PEOPLE HELP! • Pacing: Time-limited versus task completion. • Let go of perfectionism and unhealthy expectations. • Stop the “I USE to be able to …” statements.

  37. When flares happen, relax & nurture yourself-DON’T PUSH THROUGH THE PAIN!

  38. Mastering “The New Normal”: Communication Techniques • How to communicate with difficult friends/family/acquaintances (who think they are “helping”). • Keep an open mind- it may actually be good advice. • If appropriate, let them know you already have a treatment plan developed with your health care team. • If they are overly persistent, be gentle yet firm with your decline of their “advice”.

  39. Distraction works

  40. Mastering “The New Normal”: Communication Techniques (cont.) • For those who just don’t know when to stop: • Express your feelings- “I feel frustrated/ invalidated/irritated when you…” • Be patient if possible. Don’t argue, but redirect the conversation- “Be that as it may, I feel…” • Use an easy manner. Manners and humor can sometimes diffuse tense issues- “Interesting, I will ask my health care team about that.” Optional: “NOT!” (and don’t forget to flash that charm school smile!) • If all else fails, end the conversation- • “While I thank you for your concern, my health care team and I have discussed the best treatment options for me and we are doing them.” –then firmly change the subject or walk away.

  41. Mastering “The New Normal”: Resource List • Resources that may help in the journey ahead: • Websites: • The Fibromyalgia Information Foundation: ww.myalgia.com • The National Fibromyalgia Association: www.fmaware.org • Books: “The ”Complete” Idiots Guide to Fibromyalgia- Lynne Matallana • Magazines: FM AWARE • FM Support Groups- see flyer • FM-friendly exercise group

  42. Thank you for your attention!

  43. What is Wrong With My Exercise Program? Kim Dupree Jones PhD, FNP F I F

  44. Ten Things You Should Never Say to Someone with Fibromyalgia • "Well, hey, look on the bright side… At least you don't have cancer!" • “We all start to ache when we get older. Cardio-combat classes would rev you back up." • “You wouldn't have this if you just lost a few pounds." • "Is fibromyalgia a real disease? Maybe if you relaxed more…" • “You just need some vitamins." • "You should probably leave your husband and see if your fibromyalgia goes away." • "May I have some of your Vicodin? I could really use one right now for my headache." • "You should move. There must be toxins in your house making you sick." • "My neighbor has fibromyalgia and she works everyday. She says it takes her mind off the pain…“ 10. “But you look OK”

  45. Blood Flow after Dynamic and During Static Contractions of Infraspinatus Muscle (ISM) Control (n=11) FM Patient (n=10) • Standard Doppler evaluation of ISM typically shows no/small vessel perfusion. Administration of ultrasound contrast media (Levovist) allows visualization of muscle vascularity • No differences in resting vascularity of ISM between FM and control subjects • During static contraction - no detectable vascularity in FM most patients (<0.002) • After dynamic contractions - reduced vascularity in FM patients (<0.001) • Normal vascularity in the non-contracting deltoid muscle of FM patients Elvin et al. Eur J Pain. 2006;10:137-144.

  46. Exercise in FM Can Either Help or Hurt At least 59 FM intervention studies to date have used aerobics, strength and flexibility training, balneotherapy, most recently balance training Earlier studies used higher doses of exercise and resulted in greater fitness improvements but worsening symptom scores Physical functioning, fitness, fatigue, mood, stiffness, sleep and self-efficacy generally improve more than pain Exercise maintenance may improve with social support and supervision FM symptom relief may precede fitness improvement As of last month, we have our 1st exercise intervention in children with FM Jones 2007, Health Care & QOL: Busch 2008, Cochrane Database Reviews

  47. How to Overcome Postures that Worsen Pain Evaluate your posture in a mirror Where are your hands when standing? Are your shoulders pulled up and forward? Is your head pulled forward?

  48. Pain Postures

  49. Exercises to Overcome Pain Postures Stretch Your Anterior Chest

  50. Exercises to Overcome Pain Postures Strengthen Your Upper Back

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