COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
Clinical Protocol: Fibromyalgia and Chronic Pain in Related Disorders
PREAMBLE
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The recommendations below are supported by strong evidence (level A) unless stated
otherwise
We have added practical “tips”
The drugs are presented in the order (more or less) to try them
The actual order of use will depend on prior treatment, patient preference, etc.
Look for “two fors” (drugs that benefit two or more problems)
Provide patient with information/dose adjustment handout
Given the different mechanisms of action, patients often end up on 2 or more drugs
Patients with ME/CFS may need to be titrated more slowly, and may not tolerate higher doses
of medications
It is expected that physicians would educate themselves about these drugs beyond the outline
provided below
We have distinguished patient review, which can be done by nurse practitioner, from a
physician review
The treatments described below may occur one-on-one or in a group setting depending on
resources
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1. PATIENT EDUCATION
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Level A evidence
Incorporated into multiple offerings (e.g., handouts, web-based resources)
Incorporated into core group: Living with ME/CFS, FM, and related disorders
“Family and Friends” evening session
2. PHYSICAL ACTIVITY
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Graded Exercise Therapy (GET)
Level A evidence
Offered in groups: Physical Activity Group
Tai-Chi and mild Yoga
o Suggested
o Offerings in community rather than CCDP
3. SLEEP
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Sleep disturbance is a major component of FM and pain
See sleep protocol for details
4. DIET
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Emerging evidence; some RCT data
Offered in group setting
o Topic specific “one-off” groups (one session)
 Diet 101
 Low-Inflammatory Diet
o Included in disease specific groups (3 – 5 sessions)
 E.g., IBS Group
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
5. ALTERNATIVE AND COMPLEMENTARY THERAPIES
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Some agents have a strong theoretical rational and early evidence
o Co-enzyme, D-Ribose 5 g, magnesium Malate, NADH, Vitamin D
Other agents
o Evidence under review
5.1 Co-enzyme Q
 200 mg TID
5.2
D-Ribose
 5 g TID
5.3 Magnesium Malate
 250 mg QID
5.4 NADH
 10 – 20 mg daily
5.5 Vitamin D
 2000 IU daily
6. PSYCHOLOGICAL AND BEHAVIOURAL THERAPIES
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Level A evidence
Incorporated in core group: Living with ME/CFS, FM, and related conditions
o Combines Education, Pacing, CBT &, Mindfulness
o 10 weeks
o Also includes a “Family and Friends” 2 hr evening session
Incorporated in disease specific groups, e.g., IBS Group, Migraine Group
Other optional groups:
o Relaxation group
o Physical Activity group
o Mindfulness group
7. INTERVENTIONS
7.1 Trigger Point Injection, etc.
 Emerging evidence and expert opinion
 Maneuvers that resolve muscular trigger points, lengthen muscle contractures, and release
painful scars and other connective tissue restrictions
 For example:
o Myofascial release
o Trigger Point Injections
o Nerve blocks
 Currently available:
o Internally:
o Externally (outside referral):
 Change Pain Clinic
 Muscle MD
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
7.2 Acupuncture
 RCT data
7.3 Biofeedback/Neurofeedback
 Evidence under review
8. MEDICATIONS
8.1 Tricyclics
 Used for pain
 Also improves sleep architecture
 Not generally use during the day
 Watch for:
o Dry mouth
o Blurred vision
o Urinary retention
 May need to taper at higher doses when discontinuing
8.1 A Amitriptyline
 Start 5 mg 2 hrs before bed (or 12 hrs before getting up in the morning)
 Increase to 10 mg after 1 week
 Increase by 5 mg increments at 2 week intervals
 Increase to 70 mg as tolerated, depending on benefit & side effects
 Many patients cannot tolerate more than 20-30 mg
8.1 B Cyclobenzaprine
 Alternative to amitriptyline
 Also helps muscle spasms
 Start 5 mg 2 hrs before bed (or 12 hrs before getting up in the morning)
 Increase by 5 mg increments at 2 week intervals
 Increase to 20 mg as tolerated, depending on benefit & side effects
 Not generally used during the day, but occasional patients may benefit from 3 divided
doses
o 1/3 during the day and 2/3 2 hrs before bed
o e.g., 5 mg BID + 20 mg 2 hrs before bed
8.1 C Nortriptyline
 Alternative to amitriptyline
 Useful in patients who have tried amitriptyline in the past and didn’t tolerate it (usually
because it was started at too high a dose)
 Generally less benefit for pain, but also fewer side effects
 Start 10 mg 2 hrs before bed (or 12 hrs before getting up in the morning)
 Increase by 10 mg increments at 2 week intervals
 Increase to 50-70 mg as tolerated, depending on benefit & side effects
8.2 Anticonvulsants
 Used for pain
 Also helps with sleep, anxiety, dysesthesia, and restless leg
 Start with evening dosing and add during day later (1/3 day + 2/3 evening)
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
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Watch for:
o Sedation (common)
o Cognitive dysfunction
o Weight gain
o Edema
Not a good choice in obesity, metabolic syndrome, or fear of gaining weight
Topiramate may be an alternative in these populations, especially patients with migraine
(see below)
Avoid abrupt withdrawal; need to taper
Balance pain relief (benefit) with day time somnolence (side effect)
Monitor weight
Follow Brief Pain Inventory
8.2 A Pregabalin (Lyrica)
 Expensive $$$ (not a Pharmacare benefit)
 Patient dosing schedule
o Inform patients not to expect benefit until 100mg (prevent early discontinuation)
AM
Evening
25 mg
50 mg
75 mg
100 mg
Patient review at 100mg
25 mg
100 mg
50 mg
100 mg
1/3 + 2/3
Physician review for higher doses / multidrug regimens
Maximum dose 450 mg / day
 Increase dose at 1 (or more) week intervals depending on side effects (dizziness and
drowsiness are common)
 If unsure current dose is helping, trial of tapering warranted
8.2 B Gabapentin
 Alternative to pregabalin if cost is a factor (is a Pharmacare Benefit)
 Patient dosing schedule
o Inform patients not to expect benefit until 600mg (prevent early discontinuation)
AM
Afternoon
HS
100 mg
200 mg
300 mg
400 mg
500 mg
600 mg
100 mg
600 mg
100 mg
100 mg
600 mg
100 mg
100 mg
700 mg
100 mg
100 mg
800 mg
100 mg
200 mg
800 mg
100 mg
200 mg
900 mg
200 mg
200 mg
900 mg
Physician review for higher doses
Patient review at 600 mg
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
AM
Afternoon
HS
Maximum dose 3600 mg / day
 Increase dose at 1 (or more) week intervals depending on side effects (dizziness and
drowsiness are common)
 If unsure current dose is helping, trial of tapering warranted
8.2 C Topiramate
 No specific evidence for fibromyalgia
 Strong evidence for other pain syndromes
 May be useful when gabapentinoids can’t be used due to obesity, metabolic
syndrome or fear of gaining weight
o Used off-label as a weight loss drug
 Also useful if patient has migraines
 Watch for:
o Drowsiness
o Cognitive dysfunction
o GI upset
o Good water intake (prevent renal stones)
o Weight loss
 Check blood work at baseline; q month x 2, then q 6 months:
o Lytes (metabolic acidosis)
o Neutropenia
o Elevated liver enzymes
 Patients who benefit but have daytime somnolence may do better with just night time
dosing
 Patient dosing schedule
o Inform patients not to expect benefit until 50mg BID (prevent early discontinuation)
AM
Evening
12.5 mg
25 mg
50 mg
50 mg
50 mg
75 mg
75 mg
100mg
100 mg
25 mg
50 mg
Patient review at 50 mg BID
50 mg
75 mg
75 mg
100 mg
And so on…
Maximum dose 200 mg BID
 Increase dose at weekly (or more) intervals
8.3 SNRIs
 Used for pain
 Also helps with comorbid depression or anxiety, and other somatic symptoms
 If patient is currently on SSRI, consider a trial of switching from SSRI to SNRI
o Can switch from one day to the next
o Use same relative dose of SNRI (e.g., 50% of maximum dose)
 Coming off SNRI more difficult than SSRI
o Slower taper
 Tell patient to expect “transition” effects in the first 7-10 days
o Otherwise patient will think these are side effects and discontinue drug
o Patient may feel “off,” anxious, not like themselves, etc.
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Fibromyalgia and Chronic Pain in
Related Disorders
COMPLEX CHRONIC DISEASES PROGRAM
Clinical Protocol
Date: Nov 15, 2015
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Watch for:
o Agitation, insomnia
o Dyspepsia, and other GI side effects
o Sexual dysfunction
Monitor blood pressure
8.3 A Duloxetine (Cymbalta)
 Expensive $$$ (not a Pharmacare Benefit)
 Inform patient not to expect benefit for 4-6 weeks (prevent premature discontinuation)
 Start 30 mg daily (or q 2 days in drug sensitive patients)
 Increase to 60 mg daily after 3 weeks if tolerated
 Stay on 60 mg for at least 2 months before considering further dose increase
 Physician review for doses above 60 mg daily
 Above 60 mg go to BID dosing
 Can increase to 90-120 mg daily in select patients who benefit
o Usually decreased incremental benefit at higher doses and increased side effects
8.3 B Venlafaxine XR
 Alternative to duloxetine if cost is a factor (is a Pharmacare Benefit)
 Can also be tried in patients who did not tolerate duloxetine
o Venlafaxine XR comes in much smaller incremental doses
 Inform patient not to expect benefit for 4-6 weeks after reaching dose of 112.5 mg
o Prevent premature discontinuation
 Start 37.5 mg daily
 Increase by 37.5 mg increments at q 2 week intervals
 Reassess after 112.5 mg daily
 Maximum dose 225 mg daily
8.4 Canabinoids
 Used for pain
 Also helpful for anxiety, nausea, appetite, and sleep
 Can assist with opioid tapering
8.4 A Nabilone (Cesamat)
 Expensive $$$ (is a Pharmacare Benefit)
o Both 0.25 and 0.5 mg covered by Pharmacare
 Watch for:
o Drowsiness
o Cognitive dysfunction
o Dizziness
o Dry mouth
o Weight gain
 Use with caution in patients with:
o POTS (Postural Orthostatic Tachycardia Syndrome)
o NMH (Neurally Mediated Hypotension)
 Patient dosing schedule
o Can also be taken prn for breakthrough symptoms
AM
Evening/Bedtime
0.25 mg
Patient may break open a 0.5 mg capsule and take
half (if using 0.5 mg covered by Pharmacies)
0.5 mg
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
AM
Evening/Bedtime
0.25 mg
0.5 mg
0.5 mg
0.5 mg
0.5 mg
0.75 mg
0.75 mg
0.75 mg
0.75 mg
1 mg
1 mg
1mg
Patient review at 1 mg BID
Physician review for doses above 1 mg BID
Consider TID dosing at higher doses
Consider regular + prn dosing
Maximum 6 mg daily (2 mg TID)
 Dose can be increased every few days or at weekly intervals
8.5 Low Dose Naltrexone
 Only 2 small RCTs
 Used for pain
 Not to be used for patients on opioids
 May benefit patients with inflammation/inflammatory markers (e.g., co-infections)
 Usually tried only if other meds have failed
 Inexpensive drug but needs to compounded
o $$
o Compounding not usually covered
o Not a Pharmacare benefit
 Few side effects at lower doses but watch for:
o Headaches
o Dizziness
o GI sided effects
 Follow inflammatory markers if elevated at baseline
 Inform patients not to expect benefit until 4 mg daily (prevent early discontinuation)
 Start 1 mg daily
 Increase by 1 mg at weekly intervals
 Target (max) dose: 4.5 mg daily as tolerated
o Give new script for 4.5 mg dose
8.6 NSAIDs
 No evidence of efficacy in fibromyalgia (level 5D evidence)
 May benefit patients with “peripheral pain generators” (e.g., OA, back pain, etc.)
 Best used for short periods or prn
 Long term use associated with GI, renal, and cardiac side effects
 E.g., diclofenac 25-75 mg TID
 May need to provide gastro-protection
o Addition of PPI
 e.g., pantoprazole 40 mg daily
o Combination drugs
 e.g., Arthrotec (diclofenac + misoprostol)
 Expensive $$$; not covered
 e.g., Vimovo (naproxen + esomeprazole)
 Expensive $$$; not covered
 Toradol may be helpful in acute severe flares
8.7 Opioids
 Tramadol (with or without acetaminophen) may be helpful in refractory cases
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
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No evidence of efficacy for stronger opioids (level 5D evidence)
May benefit patients with “peripheral pain generators” (e.g., OA, back pain, etc.)
May want to get patients off opioids if other meds have not been tried
Tapentadol (opioid with norepinephrine reuptake inhibition) or buprenorphine patches
(opioid partial agonist) may be of benefit
Other opioids generally avoided
8.7 A Tramadol
 Expensive $$$ (not a Pharmacare benefit)
 Tramadol 50-100 mg q6h; max 400 mg / day
 Tramacet (Acetaminophen 325 mg and Tramadol 37.5 mg)
o 1-2 tabs q6h
o max 8 tablets / day
8.7 B Tapentadol (not a Pharmacare benefit)
 Expensive $$$
 Tapentadol IR (immediate release)
o For breakthrough pain
o 50-100 mg q6h prn
o Max 500 mg daily
 Tapentadol ER (extended release)
o Start 50 mg daily then BID
o Max 500 mg daily
8.7 C Buprenorphine transdermal patch
 Expensive $$$ (not a Pharmacare benefit)
 Applied weekly
 Comes in 5, 10, 15, and 20 mcg/hr patches
9. ASSESS AND TREAT COEXISTING CENTRAL SENSITIVITY SYNDROMES
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Level A evidence for most of these conditions
May require referral out
Central Sensitivity Syndromes include:
o IBS
o Migraine
o Tension Type Headaches
o POTS
o Multiple Chemical Sensitivities
o Interstitial Cystitis
o Pelvic Pain Syndromes
o Irritable Larynx Syndrome
o Restless Leg Syndrome
o Temporomandibular Disorders
o Myofascial Pain Syndrome
o PTSD
10. ASSESS AND TREAT FOR COEXISTING ANXIETY AND MOOD DISORDERS
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Level A evidence
Referral to psychiatrist for selected patients
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
11. HORMONAL ISSUES
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Testing
o TSH is part of the screening blood work for new patients
o AM cortisol can be ordered as a second-line test
o Patients requiring anything beyond this, should be referred to endocrinology
Non-Addison adrenal insufficiency
o Currently there is no evidence that patients who do not demonstrate adrenal
insufficient by validated tests such as ACTH stimulation test, CRH stimulation test
and Insulin Tolerance Test (ITT) would benefit from active glucocorticoid
replacement.
o The Clinical Advisory Committee believes that the potential harm would greatly
outweigh any perceived benefit by patients.
Patients with low TSH, low T3, and low T4
o These findings are analogous to those seen in “sick euthyroid” hospitalized patients.
o Currently, there is no role for the administration of exogenous thyroxine to these
patients. Extrapolating from this approach, CCDP patients with similar thyroid
function test findings would similarly not be given thyroid replacement therapy.
Growth Hormone
o Lower levels of IGF-1 /GH have been reported in some patients with fibromyalgia.
o Although growth hormone replacement has been explored in small series, the
potential benefit of GH replacement long- term clearly is outweighed by the risks and
cost.
Hormone Replacement Therapy (HRT) for women
o For Women, HRT is currently indicated for symptomatic management of
perimenopausal symptoms. Ongoing use of HRT is associated with increased
cardiovascular risks, venous thromboembolism, and breast cancer.
o The use of HRT should not be routine in perimenopausal women without a further
assessment of patient risks from these sex-hormone replacement.
o Further referral to subspecialists is required for these patients.
Androgen replacement in men
o Androgen replacement therapy may be indicated for those with symptoms and who
have a confirmed diagnosis of hypogonadism (decreased free testosterone levels
below the normal values).
o However, ongoing use of androgen replacement is similarly associated with the risk
of cardiovascular disease and prostate disease.
o The use of ART should not be routine in men with hypogonadism without a further
assessment of patient risks from these sex-hormone replacement.
o Further referral to subspecialists is required for these patients.
Patient with diabetes insipidus-like symptoms
o If patients are suspected to have diabetes insipidus based on a history of polyuria
and polydipsia and the absence of diabetes of mellitus, they should be referred to an
endocrinologist for consideration of a water deprivation test.
o There is currently no logistic support at BCW’s to safely perform a water-deprivation
test.
Melatonin assessment
o The Endocrinology panelist members are unaware on the implications of melatonin
assessment on the health of patients.
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COMPLEX CHRONIC DISEASES PROGRAM
Fibromyalgia and Chronic Pain in
Related Disorders
Clinical Protocol
Date: Nov 15, 2015
12. CO-INFECTIONS
Evidence under review
Patient Resources
UpToDate
CFIDS & Fibromyalgia Self-Help
Pain BC
ME|FM Society of BC
ME/FM Action Network
National Fibromyalgia Association (US)
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