“I Hurt Everywhere” “I Hurt Everywhere” Beginning the Fibromyalgia (FM) Journey? Steven S. Overman MD MPH Medical Director, Northwest Hospital Rheumatology

I Hurt Everywhere I Hurt Everywhere Beginning the Fibromyalgia (FM) Journey? Steven S. Overman MD MPH Medical Director, Northwest Hospital Rheumatology and Musculoskeletal Development Rheumatology and Musculoskeletal Development Clinical Associate Professor of Medicine University of Washington University of Washington

Chronic Widespread Pain (CWP) Prevalence: 10 13% of western populationsPrevalence: 10 13% of western populations Incidence: 5.5%/year of new cases of CWPIncidence: 5.5%/year of new cases of CWP 2% in persons without any pain 8% in persons with chronic regional pain Outcomes: at one year of CWP personsOutcomes: at one year of CWP persons 56% still had CWP (more somatic symptoms increased likelihood) 33% had regional pain 11% had no pain Croft J of MS Pain 2002;10:191-199

Predictors of CWP 2x prevalence in women ( FM is 4x )2x prevalence in women ( FM is 4x ) Persons with CWP more commonly have -Persons with CWP more commonly have - Anxiety and depression Fatigue and other somatic complaints Anxieties about health Features of somatization Dissatisfaction with health care and work Absolute differences not largeAbsolute differences not large Psychiatric diagnoses 16.9% in CWP vs 11.9% pop Croft J of MS Pain 2002;10:191-199

Relevance of CWP and Tender Points (TPs) 40% of CWP have FM (> 11 TPs)40% of CWP have FM (> 11 TPs) Some patients with no pain (5%) and regional pain (20%) had > 11 TPsSome patients with no pain (5%) and regional pain (20%) had > 11 TPs Local TPs associate with segmental painLocal TPs associate with segmental pain Depression, fatigue and sleep disorders increased as TPs rose, independent of pain complaints.Depression, fatigue and sleep disorders increased as TPs rose, independent of pain complaints. Thomas BMJ 1999:318: 1662-7 Croft BMJ 1994; 309: 696-9

FM is a Syndrome of Pain and Tenderness ACR Classification - 1990 Pain for 3 monthsPain for 3 months Generalized pain at least 3 quadrantsGeneralized pain at least 3 quadrants At least 11 out of 18 tender points painful with 4 kg of pressureAt least 11 out of 18 tender points painful with 4 kg of pressure------------------------------------------- FM is at the severe end of a spectrum of pain and tenderness disordersFM is at the severe end of a spectrum of pain and tenderness disorders Not a diagnosis of exclusion.Not a diagnosis of exclusion. FM tenderness is not limited to the 18 points.FM tenderness is not limited to the 18 points. Many feel multi-system symptoms should be present to diagnose FM.Many feel multi-system symptoms should be present to diagnose FM.

Multi-system Symptoms Found in > 50% of FM patients from the ACR 1990 Criteria for Classification Study Neck pain85%Neck pain85% Back pain79%Back pain79% Fatigue78%Fatigue78% Sleep disturbance76%Sleep disturbance76% Morning stiffness76%Morning stiffness76% Paresthesias67%Paresthesias67% Skin fold tender, trapezius60%Skin fold tender, trapezius60% Headaches54%Headaches54% Wolfe A&R 1990; 33: 160-172

Multi-system Symptoms Found in < 50% of ACR FM Study patients Anxiety 45%Anxiety 45% Sicca or dry eye symptoms36%Sicca or dry eye symptoms36% Prior depression31%Prior depression31% Irritable bowel syndrome30%Irritable bowel syndrome30% Urinary urgency26%Urinary urgency26% Raynauds phenomenon 17%Raynauds phenomenon 17%

Syndromes That Overlap With Fibromyalgia The neurologist sees chronic headache, the gastroenterologist sees IBS, the otolaryngologist sees TMJ syndrome, the cardiologist sees costochondritis, the rheumatologist sees fibromyalgia, and the gynecologist sees PMS.

Objectives To define Fibromyalgia (FM) and discuss FM as a patient labelTo define Fibromyalgia (FM) and discuss FM as a patient label Discuss the medical evaluation of FM in relationship to pathophysiologic insightsDiscuss the medical evaluation of FM in relationship to pathophysiologic insights Review evidence that can guide individual treatment decisions for patients with FMReview evidence that can guide individual treatment decisions for patients with FM

Disclosures I have no pharmaceutical grants or consulting for any FM medication.I have no pharmaceutical grants or consulting for any FM medication. I am not an Expert, just a Rheumatologist.I am not an Expert, just a Rheumatologist. A successfully trained rheumatologist is someone who can look patients in the eye all day long and say I dont know. I am not recruiting more FM patients, but I have not closed my practice either.I am not recruiting more FM patients, but I have not closed my practice either.

Definition Fibromyalgia syndrome is a chronic pain disorder with widespread tenderness. It is commonly associated with symptoms common to the affective spectrum disorders. Dysregulation is found in the nervous, immune and adrenal stress systems. A combination of bio-psychosocial factors contribute to FMS pathophysiology and influence outcomes.

Liz 40 year-old Caucasian woman with neck, back and generalized pain. Liz is an office manager and had been an avid water skier until 2 yrs. ago when she fell very hard water skiing, twisting her neck, and laying her up for several weeks. She actually never recovered noting episodes of low back pain, fatigue and increased difficulty sleeping. She started having panic episodes 1 year agon which were initially controlled with Paxil. Work is more and more difficult due to fatigue and problems with concentration. Screening Exam 14/18 tender points are positive, worse around her neck and shoulders.

#1 What do you say to Liz? 1.Tell her she has Fibromyalgia disease, which has no cures and with varying impacts on different individuals. Suggest a book or web site for her to learn about FM and return prn. 2.Tell her she a generalized pain syndrome of unclear etiology and that she will have to learn to live with it. Offer a referral to your pain psychologist and come back in 2 months. 3.Describe your findings as consistent with Fibromylagia syndrome and suggest further investigation and symptom management.

Answer to #1 1.Tell her she has Fibromyalgia disease that no cures and with varying impacts on different individuals. Suggest a book or web site for her to learn about FM. 2.Tell her she a generalized pain syndrome of unclear etiology and that she will have to learn to live with it. Offer a referral to your pain psychologist. 3.Describe your findings as consistent with Fibromylagia syndrome and suggest further investigation and symptom management.

Is Labeling someone with FM a BAD idea? It depends A population study showed that providing the label Fibromyalgia did not result in an increase prevalence, nor increase illness behavior.A population study showed that providing the label Fibromyalgia did not result in an increase prevalence, nor increase illness behavior. (White A&R (AC&R), 2002;47:260-5) The FM associated disability did not change after a claim or suit was closed. (Moldofsky J Rheum 1993:20:1935-40)The FM associated disability did not change after a claim or suit was closed. (Moldofsky J Rheum 1993:20:1935-40) Labeling promotes categorization for scientific evaluation, e.g. Lupus spectrum of illnessLabeling promotes categorization for scientific evaluation, e.g. Lupus spectrum of illness FM is not the cause, but rather the result of a variety of interacting factors. Dr O

#2 What areas need to be considered for investigation? 1.Causes of peripheral pain 2.Causes of nervous system sensitization 3.Disorders resulting from chronic distress 4.Risks for pain associated disability 5.All of the above.

Answer to #2 ALL THE ABOVE Directed by further history and exam, evaluate: Causes of peripheral painCauses of peripheral pain Causes of nervous system sensitizationCauses of nervous system sensitization Disorders resulting from chronic distressDisorders resulting from chronic distress Risks for pain associated disabilityRisks for pain associated disability

Neck Injury is associated with the development of FMS Israel study showing 21.6% of neck injury patient developed FM compared to 1.7% of leg fracture patients. (Buskila A&R 2002; 4:450-3))Israel study showing 21.6% of neck injury patient developed FM compared to 1.7% of leg fracture patients. (Buskila A&R 2002; 4:450-3)) UW study Two months after whiplash injury, 80% had TPs of FM, while 20% also had widespread pain to meet FMS classification criteria.UW study Two months after whiplash injury, 80% had TPs of FM, while 20% also had widespread pain to meet FMS classification criteria. (Robinson, World Conference on Pain, 2003)

The Over-diagnosis of FM Syndrome 321 new rheumatology referrals321 new rheumatology referrals 35 (11%) were diagnosed with FM35 (11%) were diagnosed with FM 11 (~ 34% of all FM patients) were newly diagnosed with a spondyloarthropathy MA Fitzcharles, Am J Med, 1997;103:44-50

Enthesiopathies Disease Association: Spondyloarthritis, Reiters syndrome, Reactive arthritis, Psoriasis arthritis, Crohns and Celiac associated arthritisDisease Association: Spondyloarthritis, Reiters syndrome, Reactive arthritis, Psoriasis arthritis, Crohns and Celiac associated arthritis Anatomic Locations: epicondylitis, rotator cuff capsulitis, dactylitis, trochanteric tendinitis, ilio-lumbar ligament itis, plantar fasciitis, Achilles tendinitis and SI joint, AC and costochondral joints, facet and ribs articulationsAnatomic Locations: epicondylitis, rotator cuff capsulitis, dactylitis, trochanteric tendinitis, ilio-lumbar ligament itis, plantar fasciitis, Achilles tendinitis and SI joint, AC and costochondral joints, facet and ribs articulations

Pain Response in Fibromyalgia RELATIVE PAIN

What are Clinical features of Nervous System Sensitization? Abnormal Wind-up repetitive stimulation with identical stimuli cause progressive increase in pain intensity.Abnormal Wind-up repetitive stimulation with identical stimuli cause progressive increase in pain intensity. FM patients this lasts longer (up to 2 minutes) and with more burning, stinging, and sometimes numbness, than controls Central sensitization refers to the changes that occur in the nervous system (neuroplasticity). High stimulus frequency and intensity AND reduced descending pain inhibition from the brain lead to permanent wind-up through gene transcription changes.Central sensitization refers to the changes that occur in the nervous system (neuroplasticity). High stimulus frequency and intensity AND reduced descending pain inhibition from the brain lead to permanent wind-up through gene transcription changes. The same stimulus registers at a much greater intensity when compared to a normal person.

Evidence of Nervous System Sensitization in FM In FM patients compared to controls: Functional MRI has shown enhanced sensory receptive areas and expanded fields of reception to the same pain stimulus.Functional MRI has shown enhanced sensory receptive areas and expanded fields of reception to the same pain stimulus. (Cook J Rheum 2004;31:364-78) Laser-evoked potentials in the CNS have demonstrated increased amplitudes proportional to the subjective response to skin stimulation.Laser-evoked potentials in the CNS have demonstrated increased amplitudes proportional to the subjective response to skin stimulation. (Gibson Pain 1994;58:185-93)

Peripheral Sensitization in Fibromyalgia Syndrome Trigger Points (TPs) correlate with levels of CSF substance PTrigger Points (TPs) correlate with levels of CSF substance P Epidural blocks remove pain and tenderness of TPsEpidural blocks remove pain and tenderness of TPs (Bengtsson Pain 1989; 39:171-180)

Triggers of Central Sensitization Cytokines Il-1 and IL-6 induces hyperalgesia IL-8 promotes sympathetic pain TNF alpha stimulates macrophages and microglia cells which sensitize neurons Elevation found in cases of FM cases less than 2 years duration.Elevation found in cases of FM cases less than 2 years duration. Cytokines maybe stimulated by stress, injury or inflammatory diseases.Cytokines maybe stimulated by stress, injury or inflammatory diseases. (Wallace Rheum 2001;40:743-749)

Triggers Central Pain Sensitization Functional polymorphism in the promoter region of the serotonin transporter geneFunctional polymorphism in the promoter region of the serotonin transporter gene Smokers have have higher levels of substance P in the CSF.Smokers have have higher levels of substance P in the CSF. Patients with Restless Leg Syndrome have increased hyperalgesia that resolves with treatment.Patients with Restless Leg Syndrome have increased hyperalgesia that resolves with treatment.

Modulators of Sensitization CSF pain modulators affected by wind-upCSF pain modulators affected by wind-up NMDA receptors help induce sensitization. After IV infusion Ketamine, an NMDA blocker, FM patients noted pain reduction and improved muscle endurance for 2-7. (Sorensen Scand J Rheum 1995; 24: 360-365) Substance P are 3-4 times increased in spinal fluid Serum and platelet serotonin levels are reduced in FM patients. (Wolfe J Rheum 1997; 24:555-9 )

Disorders of Distress Chronic stress causes initial increase of corticotropin releasing factor (CRF). This may lead to reduction in CRF-1 receptors and a reduction of ACTH and the cortisol response. CRF increases somatostatin causing a reduction in GH secretion.Chronic stress causes initial increase of corticotropin releasing factor (CRF). This may lead to reduction in CRF-1 receptors and a reduction of ACTH and the cortisol response. CRF increases somatostatin causing a reduction in GH secretion.

Disorders of Distress Sleep dysregulation may induce reduced growth hormone secretion and lower IGF-1 levels. Tender points develop for unclear reasons.Sleep dysregulation may induce reduced growth hormone secretion and lower IGF-1 levels. Tender points develop for unclear reasons. Other conditions with impaired cortisol secretion: chronic pelvic pain, Chronic fatigue, PTSD, overtraining syndromeOther conditions with impaired cortisol secretion: chronic pelvic pain, Chronic fatigue, PTSD, overtraining syndrome

What are Predictors of Disability? PTSD like symptoms hyper-vigilance, catastrophizing, low self-efficacy, harm avoidance, active coping (56%)PTSD like symptoms hyper-vigilance, catastrophizing, low self-efficacy, harm avoidance, active coping (56%) Limited exerciseLimited exercise Physical Function at presentationPhysical Function at presentation Depression, anxiety psychologic distressDepression, anxiety psychologic distress Pending litigationPending litigation Level of educationLevel of education

#3 Is FM primarily a Psychiatric Disorder? 1.YES It shares similar pathophysiology as the anxiety-depression spectrum of disorders. 2.NO FM is like other diseases that are made worse by or lead to stress-depression. 3.MAYBE There are studies that suggest FM is in the group of affective spectrum disorders.

#3 Primarily a Psychiatric Disorder? 1.YES It shares similar pathophysiology as the anxiety- depression spectrum of disorders. 2.NO FM is like other diseases that are made worse by or lead to stress- depression. BUT Stress factors may be necessary perpetuators to develop the full FM syndrome of pain, tenderness and somatic symptoms.

Psych Literature and FM FM non-patients had no greater number of psych diagnoses than population controlsFM non-patients had no greater number of psych diagnoses than population controls Past & current depressive disorders higherPast & current depressive disorders higher 20% of FM persons who seek any care 90% of FM patients at UW university rheum clinic had a past history of psychiatric diagnoses

Melzacks Neuromatrix Endocrine, immune, and autonomic system activity Afferent input Medullary descending inhibition Pathologic Input Central Nervous System Plasticity Attention Pain Perception Pain Behavior Psychosocial and health status factors Neuromatrix Brain areas that underlie pain experience and behavior Melzak, Pain 1999, 82 (supplement 6): S121-126

What is the Menu of Evaluations? Spine disordersSpine disorders Inflammatory disordersInflammatory disorders Infectious disordersInfectious disorders Psych disordersPsych disorders Sleep dysfunctionSleep dysfunction Endocrine dysfunctionEndocrine dysfunction Autonomic dysfunctionAutonomic dysfunction

Evaluation of Peripheral Pain Generators Neck, back, pelvis painNeck, back, pelvis pain Entheseopathy or sacroiilits routine x-rays Degenerative disc or facets routine x-rays Chiari or cervical stenosis MRI if long-tract findings Spinal stenosis or radiculopathy MRI Myofascial trigger point evaluation Ligaments, etc. injection blockade

Evaluation of Peripheral and Central Pain Generators and Sensitizers Inflammatory disordersInflammatory disorders GeneralCRP, ESR, U/A BowelEndomesial (tTG) & Gliaden Abs, ASCA ArthralgiasANA, ENA, RF, ACE SiccaSchirmers test, thyoid antibodies, ANA, ENA Raynauds? cryoglobulins, Phospholipid Ab screen, ANCA, nail fold eval., complements Infection disordersInfection disorders Pelvic symptomsProstatitis, PID, endometriosis, sacroiilitis (xray) Pharyngitis ASO titer, strept screen Hep C riskHep C antibody (Sjogrens syndrome presentation) HIV riskHIV screen (multiple rheumatic presentations) Lyme riskLyme ELISA

MANY conditions can present with as FMS RA - 14 - 54% of patientsRA - 14 - 54% of patients Lupus - 22 65% of patientsLupus - 22 65% of patients Sjogrens Syndrome - 47%Sjogrens Syndrome - 47% Hep C - 16-18% (3x controls)Hep C - 16-18% (3x controls) HIV - 29% of patientsHIV - 29% of patients Crohns disease - 49% of patients attending a university clinic in Israel but no difference in Norwegian population sample.Crohns disease - 49% of patients attending a university clinic in Israel but no difference in Norwegian population sample.

Evaluation of Central Pain Sensitizers and Behavioral Amplifiers Psych screen and concernsPsych screen and concerns All rheum new patients Screening questionnaires (depression, anxiety, panic, stressful events, past trauma or abuse, alcohol screen, function, pain, fatigue, sleep) FM patients Screen questionnaires (ADD, PTSD, Bipolar, addiction risks, personality traits and coping styles) Screen (+) patient and management problem Psychologist referral and possible MMPI, etc. (poor compliance, yes, but , controlling, marital or job distress) SleepSleep Standard questionnaires - apnea, restless legs, day-time sleepiness, fatigue refer for sleep consult / study

Evaluation Distress Disorders and Secondary Dysfunctions Endocrine evaluationEndocrine evaluation GeneralCBC, Full chemistry Thyroid disorderTSH, antibodies Menopausal statusFSH HPA axis (adrenal fatigue)AM cortisol Testosterone statusFree testosterone Other muscle painDHEA-S, IGF-1, Mg, vit D Autonomic DysfunctionAutonomic Dysfunction Postural hypotension or ^ HRTrial of salt and stockings Tilt table test Tilt table test (Geenen Rheum Dis Clinics May 2002)

FM Syndrome pain clearly depends on peripheral nociceptive input as well as abnormal central pain processing.

Liz PMH: Divorced 8 years ago and remarried 3 years ago. Had an abusive marriage. History of childhood non-sexual abuse Intermittent pelvic pain since late teenager. Diagnosed with hypothyroidism and started on treatment 6 months ago.

Liz ROS: Several years of night sweats and increasing fatigue Morning stiffness in her feet without swelling Constipation and energy are improved on thyroid Non-restorative sleep since her ski injury Dry, gritty eyes

Liz Complete PE: Very tense, but engaging and personalVery tense, but engaging and personal Skin no psoriatic pits, no rashesSkin no psoriatic pits, no rashes Thyroid - slightly enlargedThyroid - slightly enlarged CV/Pul/GI - negativeCV/Pul/GI - negative MSK Peripheral joints negativeMSK Peripheral joints negative SC and SI joints more tender than nearby tender points Neck - reduced ROM; dorsal spines tender FM tenderness - 14/18 areas + others Neuro normal strength & sensation a; no clonus; no reflex abnNeuro normal strength & sensation a; no clonus; no reflex abn

#4 - What is the appropriate work- up for Liz? (1 or more) 1.CBC, Chem Screen, ESR, CRP, ANA TSH, FSH, pelvis x-ray, psychologist referral 2.LP for substance P level in CSF 3.MRI cervical spine and functional brain imaging 4.Sleep study 5.An exercise growth hormone stimulation test

#4 - The appropriate work-up Step-wise Screening 1.CBC, Chem Screen, ESR, CRP, ANA TSH, FSH, pelvis x-ray, psychologist referral 2.LP for substance P level in CSF 3.MRI cervical spine and functional brain imaging 4.Sleep study 5.An exercise growth hormone stimulation test

Lizs Evaluation Results X-ray mild SI sclerosis and tendon calcificationsX-ray mild SI sclerosis and tendon calcifications Labs CRP = Nl, ESR = 22, thyroid Abs (+), TSH 5.3Labs CRP = Nl, ESR = 22, thyroid Abs (+), TSH 5.3 Other labs negativeOther labs negative Psychologist notes significant family relationship stressesPsychologist notes significant family relationship stresses

What is in our bag of treatment tricks? CounselingCounseling ExerciseExercise NutritionalNutritional SleepSleep Peripheral pain rxPeripheral pain rx Central agentsCentral agents EndocrineEndocrine

A Clinical Approach Patient centeredPatient centered Unique clinical issues Negotiated illness model - to develop confidence in program Understand personal values and goals Time awarenessTime awareness Chronological assessment of illness factors, symptoms and patients response to these issues Chronicity may lead to irreversibility Rehabilitation ModelRehabilitation Model Positive, hopeful, and can-do attitude Treat local impairments, monitor total function, build on individual resources and social support to limit handicap

Stuck Car Illness Model (ATime-dependent Psycho-biologic Illness Model ) Pre-morbid Are underlying problems that will cause FM or complicate recovery? Trigger events Are there recurrent triggers? Perpetuating factors Are there patient behaviors that will impair healing? Secondary conditions Are physiologic dysfunctions that may be due to the illness experience?

Lizs Pre-morbid Conditions (You may have had thin tires before you became stuck) Inflammatory - possible spondyloarthopathyInflammatory - possible spondyloarthopathy Psyche - past abusePsyche - past abuse Endocrine - hypothyroid, probable autoimmuneEndocrine - hypothyroid, probable autoimmune

Lizs Triggering Events Neck injuryNeck injury Segmental Inflammatory Acute stressAcute stress Family relations Pain

Lizs Perpetuating Factors Uncontrolled painUncontrolled pain Increased worry, frustration, fatigue, depression Behaviors that affect pain, sleep or the immune systemBehaviors that affect pain, sleep or the immune system Reduced exercise Poor sleep hygiene Tire spinning: Are you trying too hard or driving wrong for the conditions?Tire spinning: Are you trying too hard or driving wrong for the conditions? Low confidence in self-management Social discord marriage or work

Associated Conditions to be Considered in Liz DepressionDepression PTSD fear, angerPTSD fear, anger Sleep apneaSleep apnea Cognitive dysfunctionCognitive dysfunction FatigueFatigue

So What do we do for Liz? 1.Marital counseling 2.Stretching and gentle aerobic exercise 3.Diclofenac, Tylenol and possibly hydrocodone for arthritis/pain 4.Sulfasalazine for spondyloarthritis 5.Switch paroxetine to venlafaxine 6.Short-term work disability if needed

So What do we do for Liz? YES 1.Marital counseling 2.Stretching and gentle aerobic exercise 3.Diclofenac, Tylenol and possibly hydrocodone for arthritis/pain 4.Sulfasalazine for spondyloarthritis 5.Switch paroxetine to venlafaxine 6.Short-term work disability if needed

So What do we do for Liz? ALL Marital counselingMarital counseling Stretching and gentle aerobic exerciseStretching and gentle aerobic exercise Diclofenac, Tylenol and possibly hydrocodone for arthritis/painDiclofenac, Tylenol and possibly hydrocodone for arthritis/pain Sulfasalazine for spondyloarthritisSulfasalazine for spondyloarthritis Switch paroxetine to venlafaxineSwitch paroxetine to venlafaxine Short-term work disability if neededShort-term work disability if needed

Counseling Limited RCTs several show improved function for cognitive-behavorial therapy plus exercise, focused on improving functionLimited RCTs several show improved function for cognitive-behavorial therapy plus exercise, focused on improving function Bradley Curr Opin in Rheum 2002; 14:45-61 Turk, UW - 3 groups respond differently to CBT plus exerciseTurk, UW - 3 groups respond differently to CBT plus exercise Dysfuncrtional responds well Adaptive coper - minimal response Interpersonally distressed - no response Turk

Exercise Aerobic program more effective than flexibility exercise aloneAerobic program more effective than flexibility exercise alone Pool exercise or deep water walking helpful for those who cant walkPool exercise or deep water walking helpful for those who cant walk Exercise programs more effective when a part of a multi-disciplinary self-management programExercise programs more effective when a part of a multi-disciplinary self-management program Strength training can be effective additionStrength training can be effective addition Self-treatment of trigger points can be taughtSelf-treatment of trigger points can be taught Individualized or group programs for FM patients improve retention and effectivenessIndividualized or group programs for FM patients improve retention and effectiveness

Nutrition and Supplements Limited studies suggesting Vegan diet improves FM, but less than amitriptyline.Limited studies suggesting Vegan diet improves FM, but less than amitriptyline. Supplements:Supplements: Magnesium Malate 1200 mg / day showed reduction in pain only in open label phase of a RCT NADH 10 mg / day helped 30% in RCT Melatonin 3 mg HS showed improvement in sleep, global and tenderness vs a control group Crofford Currnet Rheum Reports I2001; 3:147156.

#5 - Which drugs are FDA approved for FMS treatment? 1.Amytirptyline 2.Fluoxetine 3.Zolpidem 4.Cyclobenzaprine 5.All of the above 6.None of the above

SleepCLASSGENERICBRANDMECHANISM OF ACTION DOSE TricylicantidepressntAmitriptylineDoxepinElavilSinequan 5-HT/NE RI NMDA antagonist Cation channnel bl. 10 50 mg hs SSRIFluoxetineSertalineProzacZoloft 5-HT re-up blocker 10 - 60 mg am 25 200 mg hs Narcolepsy NA Oxybate Xyrem Alpha intrusions 3 gm hs & 4hrs 2 nd genMAO Pirlindole(European) MAO A inh. Anti- epileptics Pregabalin(coming soon) soon) Ca++ channel blocker 450 mg HypnoticsZopicloneZolpidemImovaneAmbien BZ recptor agonist 7.5 mg hs 5 10 mg hs MuscleRelaxantscyclobenzaprineFlexeril 5-HT 2 antag. Anti-chol/hista 5 -30 mg hs Rao Best Prac & Research Clin Rheum 2003;17: 611-627

Peripheral Pain NSAIDs / COX IINSAIDs / COX II Number of studies have not shown benefit in FM patients. Helpful for peripheral pain generators May be important earlier in FM syndrome OpioidsOpioids Morphine shown to not be helpful in FM 14% of FM patients are on opioids, likely to help control peripheral pain Topical agentsTopical agents

Central Pain CLASSGENERICBRANDMECHANISM OF ACTION DOSE TricylicantidepressntAmitriptylineDoxepinElavilSinequan 5-HT/NE RI NMDA antagonist Cation channnel bl. 10 50 mg hs Dual RI VenlafaxineEffexor 5-HT>NE RI 375 mg / day* SSRIFluoxetineSertalineProzacZoloft 5-HT re-up blocker 10 - 60 mg am 25 200 mg hs 2 nd genMAO inhibitorPirlindole(European)Reversible MAO A inh. Anti-epilepticsPregabalin(Gabapentin)NA(Neurontin) Ca++ channel blocker 450 mg 100 4000 mg MuscleRelaxantscyclobenzaprineFlexeril 5-HT 2 antag. Anti-chol/hista 5 -30 mg hs OpioidsTramadolUltram Mu; 5-HT,NE ri 25 100 mg qid AnestheicsKetamine NMDA antag IV

Endocrine Growth hormone deficiency?Growth hormone deficiency? Symptoms: fatigue, dysphoria, impaired cognition reduced exercise capacity, muscle weakness, cold intolerance. 30% of patients have IGF-1 < 150 RCT of GH injections for 9 months 6 months in trail 15/22 experienced global improvement (p

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“I Hurt Everywhere” “I Hurt Everywhere” Beginning the Fibromyalgia (FM) Journey? Steven S. Overman MD MPH Medical Director, Northwest Hospital Rheumatology