Fibromyalgia & Chronic Fatigue Syndrome: Theories & Therapies

Mark Burger, PharmD, RPhHealth First! Pharmacy &

Compounding Center

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

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

Epidemiologyepidemiology /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

Pathophysiologypath·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

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

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)

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)

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)

Treatment of FM (Pharmacologic)

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

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”

Treatment of FM (non-pharmacologic)

• Physical Therapy & Graded Exercise• Diet [gluten-free and/or vegetarian]• Regular sleep• Stress reduction• Acupuncture• Massage Therapy• Tai Chi

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.

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.

T4→T3 Conversion

T4 De-Iodinases

Active T3

Reverse T3 (inactive)

Selenium & Zinc

Adrenaline & Cortisol

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

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!!!

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.

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]

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

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

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)

Adrenal Measurement (stress)

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

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

Universally Accepted Therapies for FM: Exercise

• REGULAR exercise• Start SLOW• Short times of walking or swimming• Stretch properly (myofascial release)• Accountability partner

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

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

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

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)

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™]

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

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

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.

Evaluation Surveys

• Adrenal Evaluation• Thyroid Evaluation– (see handouts)

Thank You

Mark Burger, PharmD, RPhwww.facebook.com/healthfirstpharmacy