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9/30/2013
Boomershine Wellness Centers
Personalized Rheumatology Care
FIBROMYALGIA 2013
MOVING BEYOND TENDER POINTS
Chad S. Boomershine, MD, PhD
Medical Director, Boomershine Wellness Centers
Medical Director, Elite Healthcare Alliance
Assistant Professor of Medicine, Vanderbilt University
330 Mallory Station Road, Suite E‐15
Franklin, TN 37067
Phone 615‐435‐3235 Fax 615‐435‐3275
Chad S. Boomershine, MD, PhD
MD and PhD degrees from the Ohio State University Internal Medicine and Rheumatology training at Vanderbilt University. Internationally recognized fibromyalgia (FM) clinician and researcher. Creator of the FIBRO System© for managing FM.1
Author of Medscape Fibromyalgia article
1Boomershine
CS. (2010) The FIBRO System: A Rapid Strategy for Management of Fibromyalgia Syndrome.
Therapeutic Advances in Musculoskeletal Disease 2(4), 187-200.
Disclosure Statement of Financial Interest
I, Chad S. Boomerhsine, DO have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation, they are: Affiliation/Financial Interest: Name of Organization (s):
Speaker's Bureau:
Pfizer, Takeda
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Disclosure Statement of Unapproved/Investigative Use
I, Chad S. Boomerhsine, DO anticipate discussing the unapproved/investigative use of a commercial product/device during this presentation. Objectives
1. Audience will change the way they diagnose
fibromyalgia.
2010 American College of Rheumatology Diagnostic
Criteria for Fibromyalgia will be reviewed.
2. Audience will change the way they think of fibromyalgia
symptoms.
Audience will learn the FIBRO mnemonic for discussing
the symptoms of fibromyalgia.
3. Audience will change the way they treat fibromyalgia.
CARES mnemonic will be reviewed that outlines the
medications used to manage fibromyalgia symptoms.
FM Epidemiology
• 3.4% of women and 0.5% of men have FM1
– Prevalence increases with age
– 80% of people with FM are undiagnosed
• Reported female:male ratio 9:1
– True ratio 4:1 female:male
– Men have fewer tender points
– Men don’t go to the doctor
– Providers don’t consider FM in men
1Wolfe
F, et al. Arth Rheum 1995;38:19-28
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FM Pain Pathogenesis1
BRAIN=PAIN
1) Injury activates
peripheral nerves
2) Excitatory signals by
peripheral nerves to
Inter-neurons = PAIN
NMDA-glutamate
Norepinephrine (NE)
Substance P
Serotonin (5-HT)
Nitric Oxide
GABA and Opioids
3) Inhibitory signals turn
off pain and reset the
system to baseline
4) Dysregulation of
excitatory and inhibitory
signals results in FM
1Bennett.
FM treatments decrease excitatory
signals and increase inhibitory
signals to restore balance
Mayo Clin. Proc. 1999, 74, 4, 385-98.
fMRI Proof: FM Patients have True Pain
Gracely RH, et al. Arthritis & Rheum. 2002, 46(5), 1333-1343.
1990 ACR Fibromyalgia Classification Criteria1
Widespread pain ≥3 months:
bilateral, above and below waist
including spine
2
1
Pain with 4kg/cm2 pressure at
≥11 of 18 Tender points:
1) Occiput- at insertion of suboccipital muscles
2) Trapezius- at midpoint of upper border
3) Supraspinatus- at origins above scapula spine
near medial border
4) Gluteal-in upper outer quadrants of buttocks in
anterior fold of muscle
5) Greater trochanter- medial and posterior to the
trochanteric prominence
6) Low cervical- anterior aspects of intertransverse
spaces at C5-7
7) Second rib- second costochondral junction just
lateral to the junctions on upper surfaces
8) Lateral epicondyle- 2cm distal to the
epicondyles
6
7
3
Back
4
Front
8
5
9
9) Knee- At medial fat pad proximal to the joint line
1Wolfe
F, et al. Rheum Dis Clin N Am 1989, 15, 1-18
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Classification Criteria miss 1/2 of FM patients1
1990 ACR Classification Criteria
15%
Clinical Diagnosis
20%
40%
26%
Stop using the ACR Classification Criteria in the clinic.2
1Katz
2J
et al., A&R 2006, 54, 1, 169-76.
Rheumatol. 2003 Aug;30(8):1671-2
FM is more than just Pain1
FATIGUE
FIBROFOG
INSOMNIA
(Unrefreshed sleep)
Depression
BLUES Anxiety
RIGIDITY (Stiffness)
Pain
OW!
Work difficulty2
OMERACT 9 Hierarcy of domains for fibromyalgia1
1Mease
P, et al, J Rheum 2009, 36, 2318-29
2Boomershine
CS and Crofford LJ Nature Rev Rheum 2009;5(4):191-9
2010 ACR FM Diagnostic Criteria
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FIBRO Diagnosis Simplified
PAIN that is Widespread (all body quadrants including spine) and Chronic (at least 3 months)
Fatigue both physical and mental (fibrofog)
Sleep – wake unrefreshed (still tired)
Symptoms must NOT be due to another condition
FM Differential Diagnosis/Labs
CBC and CMP (anemia, Paget’s, liver/renal disease, diabetes)
25,OH Vitamin D, B12 and folate levels (vitamin deficiencies)
Iron, %iron saturation, ferritin (iron deficiency if %sat <20 or ferritin <50)
TSH (Thyroid disease)
AGE‐APPROPRIATE CANCER SCREENINGS
http://www.cancer.org/Healthy/FindCancerEarly/CancerScreeningGuidelines/america
n‐cancer‐society‐guidelines‐for‐the‐early‐detection‐of‐cancer
ESR and/or CRP (inflammatory disorders‐RA/SLE but also high with obesity)
normal ESR is ½ patient age if female, ½ age ‐10 for men
Creatinine kinase, LDH, LFTs and aldolase if proximal muscle weakness (inflammatory muscle disease)
Hepatitis A/B/C, HIV, Parvo, EBV, Ehrlichia/Borrelia if risk factors
FM Differential Diagnosis
Psychologic disorders: Major depressive disorder, generalized anxiety disorders, bipolar disease, somatoform disorders
Hematologic disorders: Anemia, Leukemia, Lymphoma, Sickle Cell Disease
Endocrinologic disorders: Thyroid Disease, Hyperparathyroid
Disease, Paget’s Disease, Cushing’s Disease, Diabetes Autoimmune disorders: Polymyalgia Rheumatica, Rheumatoid Arthritis, Systemic Lupus Erythematosis, Sjogren’s Syndrome, Behcet’s Disease, Sarcoid, Vasculitidies
Infectious diseases: Human Immunodeficiency Virus, Hepatitis, Parvovirus, Lyme Disease, Epstein Barr Virus, Cytomegalovirus, Urinary Tract Infection
Neurologic disorders: Multiple Sclerosis, Myasthenia Gravis, Peripheral Neuropathy
Miscellaneous Conditions: Obstructive Sleep Apnea, Periodic Limb Movement Disorder, Restless Legs Syndrome, Cancer, Renal Disease, Vitamin deficiencies (eg, B12, folate, D), Celiac Disease (Sprue), Chiari Malformation, Drug and Alcohol Abuse
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Syndromes Associated with FM
‐
‐
‐
‐
‐
‐
‐
‐
‐
‐
Interstitial cystitis (bladder pain and inflammation) Migraine headaches
Irritable Bowel Syndrome Peripheral neuropathy
Low Back Pain and/or Sciatica
Chronic Pelvic Pain
Chest pain (Costochondritis)
Temporomandibular Dysfunction
Bursitis – Trochanteric, Shoulder, Knee, Olecranon
Tendonitis – biceps, quadriceps, hamstrings
EULAR FM Guidelines
“Optimal treatment
requires a multidisciplinary
approach … tailored
according to pain intensity,
function, associated
features, such as
depression, fatigue and
sleep disturbance …”1
1Ann
FATIGUE
FIBROFOG
INSOMNIA
Depression
BLUES Anxiety
RIGIDITY (Stiffness)
Pain
OW!
Work difficulty2
Rheum Dis. 2008; 67(4) :536-41
2Boomershine
CS and Crofford LJ Nature Rev Rheum 2009;5(4):191-9
FIBRO Problem Scale1
0 to 10 scale; 0 = NO PROBLEM and 10 = TOTALLY DISABLING PROBLEM
1. FATIGUE: How much of a problem is FATIGUE or FEELING TIRED?
2. FOG: How much of a problem is THINKING, MEMORY and/or CONCENTRATION?
3. INSOMNIA1: How much of a problem is FALLING ASLEEP?
4. INSOMNIA2: How much of a problem is STAYING ASLEEP?
5. INSOMNIA3: How much of a problem is WAKING UP FEELING REFRESHED?
6. BLUES1: How much of a problem is DEPRESSION or FEELING SAD?
7. BLUES2: How much of a problem is ANXIETY or FEELING NERVOUS?
8. RIGIDITY: How much of a problem is STIFFNESS IN MUSCLES and/or JOINTS?
9. Ow!: How much of a problem is PAIN?
10. GLOBAL: How much of a problem are all your symptoms in total (including any that are not listed above)?
1Boomershine
CS. Ther Adv Muscul Dis 2010;2(4):187-200
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FM Treatment Algorithm1
1Boomershine
CS and Crofford LJ Nature Rev Rheum 2009;5(4):191-9
FM Treatment Algorithm1
1Boomershine
CS, et al. Nature Rev Rheum 2009;5:191-9
All FM patients get P.A.I.N.1
• Prescription medications based on problematic symptoms
• Activity recommendations: Daily morning stretches along with
alternating days of aerobic and resistance exercise 6 days per week.
• Information sources: Educate and give handouts and web links:
www.fibroguide.com, http://go4life.nia.nih.gov, www.sleepassociation.org
• NO Narcotics: Avoid narcotics, benzodiazepines, and steroids
– Narcotics have poor efficacy in FM
– FM patients can have rebound pain making withdrawal of narcotics
difficult
– Regulatory issues make prescribing narcotics for fibromyalgia
problematic
– Tramadol is the only narcotic recommended to treat FM
1Boomershine
CS and Crofford LJ Nature Rev Rheum 2009;5(4):191-9
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Education and Exercise Recommendations
Self-help + Aerobic + Resistance Combination Best1
Daily morning stretches with theraband and low-impact aerobic activity
www.fibroguide.com (was www.knowfibro.com) • Comprehensive, individualized, self-directed FM management program
• Includes cognitive behavioral modules to reframe negative thinking
http://go4life.nia.nih.gov
healthy living recommendations for older people
1Rooks
DS Arch Intern Med 2007;167:2192–2200
Pharmacotherapy of FM
General points:
1) Must rule out and treat disorders that can
mimic FM before symptomatic therapies are used.
2) Medications should be started individually at low dose
and slowly up-titrated and/or combined - over half of FM
patients suffer from multiple medication intolerances.1
Multiple medications or combinations may be necessary,
ask patients what medicines worked before.
3) Medications have a limited role in FM treatment, to limit
symptoms so patients can participate in non-pharmacologic
modalities that provide long-term disease management
(exercise, behavioral, and education).2 Nonpharmacologic
therapies should be used when possible.
1Slotkoff
2Carville
AT et al. (1997) Scand J Rheum 26: 364-7
SF et al. (2008) Ann Rheum Dis 67: 536–541
Limit Polypharmacy
• The average FM patient is on 6 medications. • Review medications at first visit.
– Get rid of meds that don’t work.
– Restart meds that worked before.
• Try to find “two-fer” or “three-fer” medicines
– One medicine that serves 2 or 3 functions
– Amitriptyline at night can help sleep, pain and
depression
– Gabapentin or pregabalin at night can help sleep
and pain and anxiety
– Milnacipran in the morning can help pain and
fatigue and cognitive dysfunction
1Slotkoff
2Carville
AT et al. (1997) Scand J Rheum 26: 364-7
SF et al. (2008) Ann Rheum Dis 67: 536–541
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FM Treatment: CARES
• CNS pain modulators/anti‐Convulsants
• Anti‐depressants/Analgesics/Anti‐spasmotics
• Rest (sleep aids, treat OSA and/or RLS)
• Exercise/Education (aerobics, resistance, physical therapy, support group, web sites)
• Stretching/Stimulants/pSychotherapy
Adjuvant Nonopioid Meds for Pain
• Anti-Convulsants – 8
carbamazepine*, gabapentin*, pregabalin, topiramate, zonisamide*, ethosuximide,
lamotrigene, oxcarbazepine
• Anti-Depressants – 12
amitriptyline*, nortriptyline*, fluoxetine*, paroxetine*, buspirone *, desipramine,
venlafaxine, desvenlafaxine, duloxetine, milnacipran, velazodone, bupropion
• Anti-Inflammatories- 19
meloxicam*, naproxen*, diclofenac*, indomethacin*, ibuprofen*, ketoprofen, flurbiprofen,
oxaprozin, ketorolac, etodolac, sulindac, tolmetin, piroxicam, celecoxib, salsalate, diflunisal,
choline magnesium trisalicylate, meclofenamate, nabumetone
• Muscle Relaxers – 8
baclofen*, cyclobenzaprine*, methocarbamol, orphenadrine, chlorzoxazone,
tizanidine*, metaxalone, carisoprodol
*Indicates medicines that are on $4/month lists
1Boomershine
CS. Pain Medicine News. In Press.
FM “Anchor” drugs
• Pregabalin (Lyrica)1
– α2δ calcium channel antagonist
• Decreases presynaptic excitatory neurotransmitter release
(ascending pain pathways)
– FDA approved for FM, DPN, PHN, spinal cord injury
pain and add-on therapy for seizure disorders
– FDA approved FM dosing 150 or 225mg twice daily
• Start with 25mg with dinner/evening snack
• Up-titrate in weekly intervals as needed/tolerated
• AM dose not usually required unless patient has
severe allodynia or neuropathic symptoms
1Boomershine
CS. Journal of Pain Research, 3, 81-88
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Pregabalin: adverse reactions1
Adverse reaction
150 mg/d
300 mg/d
450 mg/d
Dizziness
23
31
43
600 mg/d Placebo
45
9
Somnolence
13
18
22
22
4
Weight gain
8
10
10
14
2
Increased appetite
4
3
5
7
1
Peripheral Edema
5
5
6
9
2
Fatigue
5
7
6
8
4
Attention disturbance
4
4
6
6
1
Memory impairment
1
3
4
4
0
Confusional state
0
2
3
4
0
Euphoric Mood
2
5
6
7
0
Vision blurred
8
7
7
12
1
Dry mouth
7
6
9
9
2
Constipation
4
4
7
10
2
http://labeling.pfizer.com/ShowLabeling.aspx?id=561
Pregabalin‐ Warnings and Precautions1
•
•
•
•
Angioedema, risk increased with ACE inhibitor use
Hypersensitivity reactions can occur
Theoretical seizure risk‐ gradually discontinue
Antiepileptic drugs, including LYRICA, may increase the risk of suicidal thoughts or behavior.
Peripheral edema‐noncardiac, increases with dose
Dizziness and Somnolence‐avoid CNS depressants and heavy machinery
Weight gain
Tumorigenic potential in mice, unknown human risk
Ophthalmological effects‐blurred vision
Creatinine Kinase Elevations
Decreased Platelet Count
PR Interval Prolongation
•
•
•
•
•
•
•
•
http://labeling.pfizer.com/ShowLabeling.aspx?id=561
FM “Anchor” drugs
• Duloxetine (Cymbalta)1
– Serotonin and Norepinephrine Reuptake Inhibitor
• Increases activity of descending anti-nociceptive
pathways
• “Balanced” 5-HT and NE reuptake inhibition
– FDA approved for FM, DPN, Chronic OA Pain,
Chronic Low Back Pain, Depression, and Anxiety
– Approved dose 60mg once daily
• Start 20-30mg with breakfast
• Up-titrate monthly if needed and tolerated
GENERIC in December 2013
1Sholz
BA, et al. Journal of Pain Research 2, 99-108
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Duloxetine: adverse reactions1
Adverse Reaction
Duloxetine
Placebo
Nausea
29
11
Decreased appetite
11
2
Dry mouth
18
5
Constipation
15
4
Diarrhea
12
8
Headache
20
12
Fatigue
15
8
Insomnia
16
10
Somnolence
11
3
Agitation
6
2
Dizziness
11
7
Orgasm Abnormal
3
<1
Libido decreased
2
<1
Ejaculation disorder
4
0
Penis disorder
2
0
Hyperhidrosis
7
1
1http://pi.lilly.com/us/cymbalta-pi.pdf
Duloxetine: Warnings and Precautions1
– Boxed warning for Suicidality in children and young adults
–
–
–
–
–
–
Hepatotoxicity risk – Monitor LFTs and avoid alcohol use
Avoid in patients with hepatic insufficiency or CrCl <30 mL/min
Blood pressure‐hypertension, hypotension/syncope and tachycardia
Serotonin Syndrome/Neuroleptic Malignant Syndrome
Abnormal Bleeding Risk
Withdrawal symptoms with discontinuation, especially when abrupt
–
–
–
–
–
–
–
Activation of mania or hypomania‐ recommend bipolar disease screen
Caution in patients with history of seizure disorder
Avoid Inhibitors of CYP1A2 or Thioridazine
Diabetics‐worsening glycemic control and slows gastric emptying
Urinary hesitancy and retention
Narrow angle glaucoma
Hyponatremia especially elderly
• dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures
1http://pi.lilly.com/us/cymbalta-pi.pdf
FM “Anchor” drugs
• Milnacipran (Savella)1
– Norepinephrine and Serotonin Reuptake Inhibitor
• Increases activity of descending anti‐nociceptive pathways
• 3:1 Norepinephrine:Serotonin reuptake inhibition in vitro
– FDA approved for FM management
– Anti‐depressant in Europe (1998) and Japan (1999)
– Approved dose 50‐100 mg twice daily
• Dose‐titration pack ‐ starts with 12.5 mg once daily
• SLOWER up‐titration improves tolerability
– I give 2 packs, have patient start 1 just in morning and add second dose in evening if tolerate 50mg qam x1 week, takes 1 month
1Ormseth
M, et al. Journal of Pain Research 3, 15-18
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Milnacipran: adverse reactions
Adverse Reaction
100 mg/day 200 mg/day Placebo
Nausea
35
39
20
Constipation
16
15
4
Vomiting
6
7
2
Dry Mouth
5
5
2
Headache
19
17
14
Migraine
6
4
3
Dizziness
11
10
6
Hot flush
11
12
2
Palpitations
8
7
2
Heart rate increased
5
6
1
Tachycardia
3
2
1
Hypertension
7
4
2
Blood pressure increased
3
3
1
Hyperhidrosis
8
9
2
1http://frx.com/pi/Savella_pi.pdf
Milnacipran:
–
–
–
–
–
–
–
–
–
–
–
–
Warnings and Precautions1
Boxed warning for Suicidality in children and young adults
Hepatotoxicity risk – Monitor LFTs and avoid alcohol use
Blood pressure‐hypertension, hypotension/syncope and tachycardia
Serotonin Syndrome/Neuroleptic Malignant Syndrome
Abnormal Bleeding Risk
Withdrawal symptoms with discontinuation
Theoretical risk for activation of mania or hypomania
Caution in patients with history of seizure disorder
Avoid in patients with substantial alcohol use or chronic liver disease
Urinary hesitancy and retention
Narrow angle glaucoma
Hyponatremia
50% dose ↓ Severe Renal Impairment (CrCl <30 mL/min)
1http://frx.com/pi/Savella_pi.pdf
Which to choose?
• Direct efficacy comparisons impossible1
– Pregabalin if sleep problems predominate
• Limit daytime use if fatigue or cognitive dysfunction severe
– Duloxetine if depression or anxiety predominate
• Avoid if renal/liver dz; caution in diabetes, migraine, insomnia, IBS
– Milnacipran if fatigue or cognitive dysfunction predominate
• Avoid in liver disease; caution in IBS, migraine
• Combination therapy may be beneficial
– Decreased pain with gabapentin‐venlafaxine combination in DPNP patients who failed gabapentin mono‐therapy2
– Pregabalin + milnacipran better in FM patients who failed
pregabalin mono‐therapy3 with reduced severity of side effects
1Boomershine
2008 Nat Clin Pract Rheum 12: 636-7
DA 2001 J Clin Neuromuscul Dis 3: 53–62
M, et al. Ann Rheum Dis 2010; 69: 448
2Simpson
3Farmer
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NON-FDA Approved Substitutes
• Older specific serotonin reuptake inhibitors (SSRIs) have norepinephrine activity and can improve FM symptoms at high doses (fluoxetine 80mg/d)1
– Combine SSRI with an agent that inhibits norepinephrine reuptake such as TCAs (amitriptyline), trazadone, or amoxetine (Strattera)
– Amitriptyline 25mg qhs + fluoxetine 20mg qam
– Risk for serotonin syndrome when combining serotonin‐active drugs
• Amitriptyline provides balanced norepinephrine and serotonin re‐uptake inhibition and has been shown in multiple meta‐
analyses to be effective in FM patients2,3
• Gabapentin mean dose 600mg tid has efficacy in treating FM4
1Am
J Med. (2002) 112: 191-7
2Arth
Rheum (2008) 59: 1279-98
(2008) 47: 1741-6
Rheum (2007) 56: 1336-44
3Rheum
4Arth
Fatigue and Fibrofog
• Non‐stimulant wakefulness promoting agents
– Modafinil (Provigil)
• FDA‐approved for obstructive sleep apnea (OSA), narcolepsy, and shift‐work‐syndrome
• 3 reports supporting use in treating FM fatigue1,2,3
– Doses ranged from 50‐400mg daily given as a single am dose or divided morning and noon
– ?Armodafinil (Nuvigil) active enantiomer of modafinil
• Stimulants‐ methylphenidate (Ritalin), dexmethylphenidate (Focalin), amphetamines (Adderall)
– Methylphenidate 5‐10mg qam and noon
• SR preparation allows once daily dosing
1J
Clin Rheum (2007) 13: 52
Clin Rheum (2003) 9: 282-5
3J Neuropsych Clin Neurosci (2001) 13: 530-1
2J
Insomnia Evaluation
• Identify specific sleep problem
• Restless legs syndrome(RLS), obstructive sleep apnea(OSA)
– RLS in 1/3 of FM patients, screen using RLS Study Group criteria1
• Have you ever experienced a disagreeable feeling in the legs, with
aching, creeping, and motor restlessness, with an urge to move the
legs? If answer YES, ask:
– Do these symptoms appear mainly when sitting or lying down?
– Are these symptoms worse at night?
– Is any relief of these symptoms obtained by leg movement or
walking?
Patient Berlin Questionnaire criteria2 should have formal sleep study
• Persistent snoring and daytime somnolence and hypertension or
obesity predicts OSA with 86% sensitivity and 77% specificity2
• Epworth Sleepiness Scale is very poor at identifying OSA
1Movement
2Ann
Disorders (1995) 10: 634-42
Intern Med (1999) 131: 485-91
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Insomnia Treatments
• Benzodiazepines should be avoided in FM patients
• Sedating antidepressants can benefit depressed patients
• Ramelteon (Rozerem) and eszopiclone (Lunesta) are recommended FDA approved therapies for insomnia, zolpidem (Ambien) 2nd line
– Ramelteon is a selective melatonin receptor agonist given as 8mg tablet 90 minutes before bedtime followed by a hot shower
• Usually well tolerate, no sedation, no “hang‐over” the next day
– Eszopiclone is a nonbenzodiazepine hypnotic given as a 1, 2 or 3mg tablet immediately before bedtime
• Patients should be monitored for worsening depression or suicidal ideation • Use with other sedatives should be avoided
– Headache and dysgeusia (unpleasant taste sensation) can limit tolerability
Zolpidem dosing 50% maximum in women due to sedation risk
• Sodium Oxybate (Xyrem or GHB)
– Improves sleep and global FM symptoms1
– Indication rejected due to safety concerns
1Russell
IJ, et al. Arthritis Rheum. 2009;60:299-309
Sedating Antidepressants
• Tricyclic antidepressants (TCAs): amitriptyline, desipramine, nortriptyline, and cyclobenzaprine
– Low evening doses (5‐10mg cyclobenzaprine, 10‐50mg amitriptyline)
– Intolerance to higher doses often makes TCA monotherapy insufficient to manage FM or mood disorders
– Combining low‐dose TCAs with fluoxetine 20mg daily can provide synergy for treating FM symptoms with minimal side effects1
• Mirtazapine (Remeron) enhances serotonergic and noradrenergic neurotransmission via a novel mechanism – May allow use in patients who do not tolerate traditional SNRIs
– 15‐30mg at night improves FM pain, insomnia, fatigue, depression2
– Somnolence inversely proportional to dose, increase if too sedating
• Trazodone is the most sedating antidepressant
– 100mg qhs improves sleep architecture3
1J
Clin Psychiat (2008) 69 (suppl 2): 25-30
2Pharmacopsychiatry
3Neuropsychobiol
(2005) 37: 168-70
51: 148-63
RLS Management
• Replete Iron stores
– Ferritin should be ≥50ug/L (100 optimal), %iron saturation ≥20%1
• If inflammation present, divide ferritin by 3 to get true value
• soluble transferrin receptor (mg/L)/ferritin (mcg/L) ratio
– If <1 likely anemia of chronic disease, if >2 likely iron deficiency anemia
• Dopamine agonists
– Pramipexole (Mirapex) and ropinirole (Requip) approved for RLS
– Both have demonstrated efficacy in managing FM2,3
– Start at low dose (0.125mg for pramipexole and 0.25mg for ropinirole) 2 hours before bedtime
– Increased in weekly intervals until RLS symptoms resolve or patients become intolerant
• Recommended maximum doses for RLS: pramipexole 0.5mg and ropinirole 4mg
• Higher doses for FM symptoms (mean 4.5mg for pramipexole and 6mg for ropinirole)
– Generic carbidopa/levodopa (25 and 100mg, respectively) combination tablets can be used to treat RLS off‐label
1Sleep
2Arth
3J
Med Reviews (2001) 5: 277-86
Rheum (2005) 52: 2495-505
Clin Rheum (2003) 9: 277-9
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Antidepressants
• FM patients often have major depressive disorder (30%) or an anxiety disorder (40%) • Duloxetine is recommended first‐line treatment
– Milnacipran monotherapy doesn’t work well for depression in FM • Desvenlafaxine (Pristiq) generic SNRI, similar to Cymbalta
• Venlafaxine (Effexor) is generic SNRI shown to improve FM symptoms at dose of 75mg once daily1
• Older selective serotonin reuptake inhibitors (SSRIs): fluoxetine (Prozac) and paroxetine (Paxil)
– Inhibit norepinephrine reuptake at 40‐80mg per day
– High doses often poorly tolerated
SNRIs should be gradually tapered as rebound
increases in depression and withdrawal
symptoms may occur
1Sayar
et al. Ann Pharmacother 2003;37(11):1561-5
Stiffness Treatments
• Daily morning stretching
• Cyclobenzaprine (Flexeril)
– A tricyclic antidepressant (TCA)
– Significantly improves global FM symptoms along with pain, sleep, and tender points1
– 30‐50mg divided over the day can manage FM “flares”
• Dose typically limited by sedation
• Nightly 15 or 30mg extended release (Amrix) is less sedating2
– Monitor for worsening fatigue and anticholinergic side effects (dry mouth, urinary retention, etc.) – Avoid use with other CNS depressants
1Arth
Rheum (2004) 51: 9-13
2http://www.amrix.com/pdf/AMR-001b_072808_Blueline.pdf
Stiffness Treatments
• Tizanidine (Zanaflex) is central α2‐adrenergic agonist
– Start with 4mg qhs, maximum dose of 36mg divided over the day
– Along with anticholinergic side effects, tizanidine can cause hepatotoxicity
and laboratory monitoring is strongly recommended
• Methocarbamol (Robaxin) and metaxalone (Skelaxin)
– Less sedating, limited published evidence in managing FM
• Antispastics (baclofen and dantrolene) can be helpful especially in FM patients with muscle cramps
• Benzodiazepines should be avoided in FM patients due to addiction potential and worsening of nonrestorative sleep.
• Tramadol can significantly improve FM stiffness and will be discussed in the next section.
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Analgesics
• Acetaminophen (APAP) has proven efficacy in FM
– Treatment failures are common since required dosing is near 4000mg/day and usually divided 6‐8 times per day
– Compliance can be improved using extended‐release formulations of 1000mg four‐times daily
– Known APAP hepatotoxicity‐ lab monitoring required
• Most patients prefer NSAIDs over APAP1
– Evidence for efficacy of NSAIDs in FM is lacking – NSAIDs are not recommended in the absence of a concomitant inflammatory condition or OA/bursitis that can serve as a pain generator in FM
1Arth
Rheum (2001) 44: 2451-5
Tramadol (Ultram)
• Traditional narcotics should be avoided in FM treatment
– Poor Efficacy and can cause Rebound Pain
• Tramadol is a narcotic combining mu‐opioid agonist and SNRI activities recommended for managing FM1
– One or two tramadol/acetaminophen 37.5/325mg tablets taken 4 times daily can significantly improve pain, stiffness and work interference in FM patients2
– Side effects include nausea, pruritis and constipation
– Risk of abuse and dependence is low
• 97% of cases occur in patients with a prior history of substance abuse3
• Recommend screening for prior substance abuse before prescribing
• Tapentadol (Nucynta)
– Weak mu‐opioid agonist with NRI activity
– Acute pain indication only
1Ann
2Arth
Rheum Dis (2008) 67: 536–541
Rheum (2005) 53: 519-27
Alcohol Depend (1999) 57: 7-22
3Drug
Conclusions
• FM patients can be very rewarding to treat
• Identify and treat disorders that can mimic FM
• Pharmacologic therapies work best when combined with nonpharmacologic treatments
• The FIBRO mnemonic with the FIBRO Problem and Change Scales provide a rapid, symptom‐
based method for assessment and management of FM patients designed for use in busy clinics
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Boomershine Wellness Centers
Personalized Rheumatology Care
FIBROMYALGIA 2013
MOVING BEYOND TENDER POINTS
Chad S. Boomershine, MD, PhD
Medical Director, Boomershine Wellness Centers
Medical Director, Elite Healthcare Alliance
Assistant Professor of Medicine, Vanderbilt University
330 Mallory Station Road, Suite E‐15
Franklin, TN 37067
Phone 615‐435‐3235 Fax 615‐435‐3275
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