This document reviews fibromyalgia and chronic fatigue syndrome, discussing their definitions, epidemiology, pathophysiology, symptoms, theories of causation, and treatment options. It examines various theories that fibromyalgia may be caused by abnormalities in brain chemistry, hormones, muscle and cell function. Both pharmacological and non-pharmacological therapies are considered, including medications, diet, exercise, sleep, and supplements. Specific evaluation and treatment approaches focused on the thyroid, adrenals, sleep, fatigue, stress reduction, and pain management are outlined.

1. Fibromyalgia & Chronic Fatigue
Syndrome: Theories & Therapies
Mark Burger, PharmD, RPh
Health First! Pharmacy &
Compounding Center

2. Objectives
• Review the basic information on fibromyalgia
and chronic fatigue syndrome
• Examine various theories on the cause(s) of
FM and CFS
• Consider pharmacologic and non-
pharmacologic therapies for FM and CFS
• Explore new approaches to the treatment of
FM, CFS and related syndromes

3. Fibromyalgia (FM)
• DEFINITION :: A common condition associated
with muscular pain, fatigue, and modd
changes;
• DEFINITION :: A history of widespread, “all
over” pain of at least 3 months duration with
abnormal pain sensitivity in at least 11 of 18
specific sites (tender points)
– American College of Pharmacy definition

4. Epidemiology
epidemiology /ep·i·de·mi·ol·o·gy/ (-de″me-ol´ah-je) the science concerned
with the study of the factors determining and influencing the frequency and
distribution of disease, injury, and other health-related events and their
causes in a defined human population. Also, the sum of knowledge gained in
such a study.
• Present in most countries and most ethnicities
• Present fro ages 30 to 50
• Affects, primarily, women
– Ratio of F:M = 9:1
• More prevalent in older patients
– i.e. > 50 years old

5. Pathophysiology
path·o·phys·i·ol·o·gy (pth-fz-l-j)n.1. The functional changes
associated with or resulting from disease or injury.
• No “real” cause has been determined
• Can not be diagnosed w/lab tests, x-rays, or blood tests
• Ultimately comes down to altered pain perception & is
recognized as a form of chronic pain syndrome
• Decreased REM sleep is seen
• Psychololgical abnormalities seen:
– Depression
– Anxiety
• Langford, C, Gilliand, B, “Chapter 329: Fibromyalgia”,
Harrison’s Principles of Internal Medicine

6. Symptomology
• Muscle pain
• Fatigue
• Stiffness
• Anxiety
• Depression
• Headaches
• Decreased Quality of Life (QOL)
– Langford, C, Gilliand, B, “Chapter 329: Fibromyalgia”,
Harrison’s Principles of Internal Medicine

7. Brain Chemistry & Hormonal Abnormalities
Commonly Seen in Fibromyalgia 1 of 2
• ↓ serotonin (an inhibitory neurotransmitter
found in the brain & gut)
• ↓ stress hormones due to defects in the
feedback loop from the adrenal glands to the
brain (pituitary)
– ↓ norepinephrine (NE) an excitatory
neurotransmitter. A “fight-or-flight” hormone
– Altered cortisol (a long-term “f-or-f” hormone)
• Decreased Insulin Like Growth Factor (IGF) which
is an indicator of Growth Hormone (HGH)

8. Brain Chemistry & Hormonal Abnormalities
Commonly Seen in Fibromyalgia 2 of 2
• Decreased DHEA (an adrenal hormone). Highest
in 3rd decade of life & gets lower as we age. Can
be tested in saliva as DHEA-S
• Decreased Thyroid Hormone (especially T-3)
• Decreased Melatonin
• Increased Substance-P (a neuromodulator &
neurotransmitter associated with the regulation
of mood disorders, anxiety, stress,
reinforcement, neurogenesis, respiratory rhythm,
neurotoxicity, nausea/emesis, pain and
nociception or pain perception)

9. Abnormalities in the Muscle and Cell
• Biochemical abnormalities resulting in ↓ ATP (ATP is
considered as the universal energy currency for
metabolism: ATP→ADP + Energy)
• Structural blood flow abnormalities particularly
regional cerebral blood flow (rCBF)
• Functional abnormalities due to pain and stress
(Functional abnormalities or functional deficiencies
can become a problem for the entire body. E.g. if your
shoulder or an area of your spine loses optimal
function, the workload and physical stress of that body
part is distributed to other areas of the body)

10. Treatment of FM (Pharmacologic)
• Lyrica®, Cymbalta®, Savella®
• Tricyclic antidepressants (Elavil®, etc.)
• Cyclobenzaprine (Flexeril®, etc.)
• SSRIs (Prozac®, Paxil®, etc.)
• Analgesics (Tramadol®)
• Anticonvulsants (Neurontin® aka gabapentin)

11. Adverse Effects Considerations for
Pharmacologic Agents
• Angioedema (rapid swelling or edema of the skin,
subcutaneous tissue, mucosa & submucosal
tissues)
• Suicide ideation
• Dizziness, sleepiness
• Weight gain
• Headache
• Quality of Life (QOL) issues
• “One Size (does not) Fit All”

12. Treatment of FM (non-pharmacologic)
• Physical Therapy & Graded Exercise
• Diet [gluten-free and/or vegetarian]
• Regular sleep
• Stress reduction
• Acupuncture
• Massage Therapy
• Tai Chi

13. Theories as to cause of FM
• “A large body of evidence supports the
relationship between stress and altered
activity in both the sympathetic nervous
system and hypothalamic-pituitary-adrenal
(HPA) axis [aka the “feedback loop for cortisol
and stress”].”
– The Journal of Rheumatology 2005. Vol. 32,
supplement 75.

14. Theories as to cause of FM
• Given the complexity of the symptoms associated
with FM, disturbances in the endocrine
(hormonal) system may account for some of the
associated symptoms of fibromyalgia.
• Proposed by John Lowe: Symptoms of FM are
due to inadequate thyroid conversion
↓(T4→T3). The key to proper thyroid
measurement & evaluation is NOT thyroid
production, but thyroid conversion, uptake, &
utilization.

15. T4→T3 Conversion
Active T3
Selenium & Zinc
T4 De-Iodinases
Adrenaline & Cortisol
Reverse T3
(inactive)

16. • Thyroid hormone controls metabolism.
Therefore, poor thyroid utilization could
create a hypometabolic (low metabolism)
state in FM patients.

17. Treatment per Lowe
• FM low thyroid patients need T4/T3
supplementation
• FM hypometabolic patients need T3
supplementation
• As metabolism increases, symptoms of FM
decrease
• RULE: Treat the patient, NOT the blood
tests!!!

18. FM and Dopamine (DA) Dysfunction
• Proposed by Patrick Wood
• Wood looks at FM as a stress-related disorder.
• Wood believes that prolonged exposure to
unavoidable stress produces a reduction in DA
output and development of hyperalgesia
(heightened pain perception)
• According to Wood, both serotonergic &
dopaminergic systems are impacted, but the
effect on DA appears to outlast the effect on
serotonin.

19. Treatment according to Wood
• Emphasis on total body stress, not just pain
• Uses comprehensive approach
• Suggests the use of Mirapex®/pramipexole a dopamine
agonist (sits on DA receptors)
• Melatonin
• DHEA [cream, capsule, troche ... Compounded Rx]
• T3 [Slow Release: Compounded Rx]
• Phosphatidyl serine + adrenal support
• Cortisol [Cortef® or IsoCort™ or Compounded Rx]
• Magnesium malate or Dextromethorphan for pain
• Mucuna pruriens ext. [DopaTropic Powder™/Biotics]

20. Other Approaches in the treatment of
FM
• Myofascial approach (the junction of the
fascia and the muscle) Fascia is the soft tissue component of
the connective tissue that provides support and protection for most
structures within the human body, including muscle. This soft tissue can
become restricted due to psychogenic disease, overuse, trauma,
infectious agents, or inactivity, often resulting in pain, muscle tension, and
corresponding diminished blood flow.
• This may explain the success of localized
“trigger point” therapies

21. “What can I do to address my FM
problem?”

22. Thyroid Measurement (metabolism)
• Evaluation survey/questionnaire
• Basal Temperature measurement
– In AM
– Immediately upon awakening
– Analogue thermometer, mercury-free
– Thyroid tests that measure T4→T3 conversion
– Treatment with dessicated thyroid or a T4/T3
combination ... NOT levothyroxine (aka T4)

23. Adrenal Measurement (stress)
• Evaluation survey / questionnaire
• Saliva cortisol measurements (4 point)
• Saliva DHEA measurement (in AM)
• Adrenal Support
• Treatment with cortisol or DHEA

24. Universally Accepted Therapies for
FM: Diet
• Well balanced diet (gluten-free or vegetarian)
• Small meals (4-5 per day)
• Fruits
• Vegetables
• Whole grains
• Skinless poultry and fish
• Eliminate caffeine, sugar, and alcohol

25. Universally Accepted Therapies for
FM: Exercise
• REGULAR exercise
• Start SLOW
• Short times of walking or swimming
• Stretch properly (myofascial release)
• Accountability partner

26. Universally Accepted Therapies for
FM: Sleep
• Establish and maintain normal sleeping
routine
• Avoid caffeine and drinking for the entire day,
not just at night. Caffeine can alter cortisol for
24 hours after drinking
• Consider switching medications from bedtime
to morning

27. Universally Accepted Therapies for
FM: Stress Reduction
• Avoid stress triggers
• Use stress reduction techniques (meditation,
breathing, Tai Chi, Quigong, walks in Nature.
• Find enjoyable activities/hobbies
• Use support groups

28. Supplements
• ↓ inflammation with MEDICAL FOODS (e.g.
UltraInflamx™)
• ↓ inflammation with Fish Oil 1200-1500
mg/day (esp. the ones high in EPA)
• Curcumin w/absorption enhancement
• Improve mitochondrial function w/CoQ-10
and mitochondrial numbers w/PQQ & Resv.
• Improve mitochonrial energy w/L-carnitine
• Improve energy production w/Resveratrol

29. Reducing localized pain
• Ibuprofen, Diclofenac, Ketoprofen Transdermal
Gels (Rx-compounded)
• Capsaicin Creams [works on Substance P] (Rx-
compounded)
• Magnesium glycinate, -citrate, -malate 1200-
1800 mg per day
• Ribose, 2.5-5.0 Gms. Twice daily (Corvalen-M™)
• Magnesium 20% Topical Cream (Rx-compound)

30. Fatigue (Thyroid Based): Following
appropriate eval + testing
• Thyroid support products
• Iodine + Tyrosine (tyrosine is the main
building block of the thyroid hormone. It is an
amino acid)
• Ribose (a sugar that enters into an alternate
pathway to provide energy after the usual
sources have been depleted) [Corvalen-M™]

31. Fatigue (Stress/Adrenal Based):
Following appropriate eval + testing
• Adrenal Support Products
• Adreset™
• Adren-ALL™
• Rhodiola, Ginseng, Ashwaganda, Astragalus,
Holy Basil, Maca, Licorice, Cordyceps
(adaptogens)
• Ribose

32. Sleep (problems with sleep can be
MORE problematic than pain
management)
• Goal is to restore normal sleep cycles & sleep
activity
• Therapy should be non-addictive
• Non-interactive with other medications
• Customized to needs of patient

33. Sleep Supplements
• Melatonin SR capsules (Rx-Compounded)
• Phosphatidyl Serine Complex(PS)
• L-theanine (an amino acid found in tea)
• “Sweet Dreams” [L-theanine + Melatonin +
Hops + Phosphatidyl Serine + P-5-P + Lemon
Balm] (Rx-Compounded)
• Magnesium Malate (or glycinate) at bedtime
• Chamomile, passionflower, valerian, skullcap.

34. Evaluation Surveys
• Adrenal Evaluation
• Thyroid Evaluation
– (see handouts)

35. Thank You
Mark Burger, PharmD, RPh
www.facebook.com/healthfirstpharmacy