Fibromyalgia 2

FIBROMYALGIA

FIBROMYALGIASteven Smith, NPMontgomery, Alabama

CONFLICT OF INTEREST STATEMENT:

Steven Smith, NP has in years past been on the speaker bureau for Pfizer Inc though not currently. This CE activity was compiled without the aid of any pharmaceutical company. The medications and products mentioned in this activity will be presented in a fair and balanced way.No ink pens or coffee cups were received in exchange for endorsement of any pharmaceutical product mentioned in this presentation.

WHAT IS FIBROMYALGIA SYNDROME?Is it a musculo-skeletal disorder?


Is it a mental condition or is it all in their heads?



Is it an inflammatory, rheumatologic problem?



Is it an inflammatory, rheumatologic problem?

Is it an illness of the central nervous system?

FMS is thought to be an illness of the

CENTRAL NERVOUS SYSTEM

And even more, an illness of the

NEURO-ENDOCRINE SYSTEM

FMS is thought to be one of the many

CENTRAL SENSITIZING SYNDROMES

What is CENTRAL SENSITIZING SYNDROME?

Afferent (conducting inward) sensory input into

THE DORSAL HORN GANGLION

of the spinal column overwhelm the

GATED PROTECTIVE MECHANISMS

so that you get a

WIND-UP PHENOMENON.

What is a WIND-UP PHENOMENON?

It is NEURON HYPEREXCITABILITY with a LOW DISCHARGE THRESHOLD that worsens with each sensory input (pain, touch, movement, any sensory input). This creates an EXAGERATED DISCOMFORT in people with CENTRAL SENSITIZATION SYNDROME.

FMS is thought to be one of several CENTRAL SENSITIZING SYNDROMES.

Others include:

IRRITABLE BOWEL SYNDROMEIRRITABLE BLADDER SYNDROME CHRONIC PELVIC PAINCHRONIC FATIGUE SYNDROMECHRONIC T M JCHRONIC HEADACHERESTLESS LEG SYNDROME

THERE IS OFTEN OVERLAP AMONG THESE CONDITIONS

Also overlapping with FMS are a higher prevalence of coexisting psychopathology:

DepressionGAD/Panic Disorder (responds best to FMS Tx)PTSD (responds worse to FMS Tx)Bipolar Disorder (responds worse to FMS Tx)InsomniaOCD

Pain pathways are a two-way street.

There are AFFERENT, conducting inward, ascending pain pathways,

(Pain towards the brain) or (Pain on a train trying to gain toward the brain)

ANDAmeliorating, inhibitory, descending pain pathways.

(Drain the pain from the brain) or(Train the pain to wane)

Some of the neurotransmitters involved in the ASCENDING pain pathways are:

Substance PGlutamate and other excitatory amino acidsNeurotrophinsNerve Growth FactorBrain Derived Neurotrophic Factor

These are found in higher levels in the CEREBRAL SPINAL FLUID of patients with Fibromyalgia

Some of the neurotransmitters involved in the DESCENDING pain pathways that inhibit pain are:

NorepinephrineSerotonin

The metabolites of these were found to have LOWER levels in the Cerebral Spinal Fluid of patients with Fibromyalgia.

! WAIT !I THOUGHT PAIN WAS A BRAIN THING

In one FMS study, they apply painful stimuli to both FMS patients and a normal control group while performing an MRI observing the increased activity in the areas of the brain related to pain.

It took only half of the painful stimuli to light up these brain areas in the FMS patients than the control group.

The FMS patients have an increase in the gain or sensitivity on their CB radios OR have an increased volume control on their MP3 players of pain.

So, what does this have to do with PHARMACOLOGY?To treat FMS appropriately, you must understand:The Neurotransmitters you want to increase and decrease.The Receptors you want to block.The Neurons that you want to control hyperexcitability.The ascending, descending, and brain pathophysiology of the CNS of the FMS patient.If you understand this you will also understand what pain ameliorating therapies NOT to use.

TWO GREAT TRUTHS

You will not adequately treat what you cannot diagnose.Richard Sobel, MD, mentor

If you do not know how to diagnose Fibromyalgia then this pharmacology lecture is useless.Steven Smith, NP, mentee

FIBROMYALGIA is a diagnosis of EXCLUSION.

That is why FMS is a Syndrome and not a Disease. There is no specific test for FMS.

Diagnosing FMS take the good old fashioned hard work of a good HISTORY AND PHYSICAL EXAM(i.e.. SOAP)

HISTORY AND PHYSICAL EXAM

S.CC, HPI, PMH, SocH, PsychH, FH, ROS

O.PHYSICAL EXAM, DIAGNOSTIC TESTS

A.ASSESSMENT/DIAGNOSIS

P.PLAN

Name: _________Date:_______ Age:_39_Sex: __F__

FMS affects 3 million to 8 million people in the U.S.Age is usually between 20 and 60 years old.Over 80% of those diagnosed with FMS are female.Mostly occurs in females of reproductive age.

S - SUBJECTIVECHIEF COMPLAINT: Rarely I think I have 14/18FMSMore often:Im depressedI cant sleepIm tired all the timeAND I hurt all over

Legitimizing statement: Im afraid Im going to lose my job.

20% apply for disability50% leave the workforce

HISTORY OF PRESENT ILLNESSFMS

Onset/duration: A while.>3 mo.Location: My neck and my back4quadsSeverity: a 6 out of 10Quality: Its hard to describe, it just hurts.Modifying factors:I was in a wreck 2 years ago.My friend was killed.

HISTORY OF PRESENT ILLNESSFMSModifying factors:I was in a wreck 2 years ago.My friend was killed.

Modifying factors in FMS:Acute traumaImproper body mechanics, Abnormal postureInfection, InflammationPsycho-social stressorsMetabolic imbalance

HISTORY OF PRESENT ILLNESS

Associated signs and symptoms:I wake up tired, Im depressed, My nerves are shot, I dont sleep well,Im gonna lose my job

Associated signs/symptoms in FMS:Cognitive impairment, poor sleep, fatigue, morning stiffness, anxiety, depression, impaired social function, impaired occupational functioning, sexual dysfunction

HISTORY OF PRESENT ILLNESS

Current Treatment: Goody Powders didnt help but I took a friends Lortab and it helped. I been on Prozac since my 1st marriage ended.

Treatment with FMS:Will NSAIDs help FMS?Will SSRIs help FMS?Will narcotics help FMS?

CURRENT MEDICATIONS:

Prozac 10mg qdXanax 0.5mg BIDGoody PowdersCoQ 10

Will these help Fibromyalgia pain?

PAST MEDICAL HISTORY:Fatigue, Trauma/MVA, Insomnia, Obesity

PSYCH HISTORY:Generalized Anxiety DisorderDepressionAbused by 1st husband

Common comorbid psychiatric conditions with FMS:GAD, Depression, PTSD, Bipolar Disorder

PAST SURGICAL HISTORY:

C-Section x 2Tubal ligation

FAMILY HISTORY:

Father: IBSMother: Depression, Migraine2 Children: ADHD

There is a strong genetic predisposition for FMS with the other CENTRAL SENSITIZATION SYNDROMES (CSS) in family members.

REVIEW OF SYSTEMS:FMSConstitutional:FeverNoFatigue70%Sleep apneaWeight changeInactivityEnergy levelDown

REVIEW OF SYSTEMS:FMS

Eyes:r/o inflam, neuroENT:r/o infectionPulmonary:r/o infection, asthmaCardiovascular:r/o CV disease

REVIEW OF SYSTEMS:FMS

GI:Abd pain40% have IBS symptomsConstipationN/V/DBleeding

REVIEW OF SYSTEMS:FMSGU:Dysuria/Frequencyr/o infectionIncontinenceI.C. (CSS)Nocturiar/o metabolicIr. Bladder Sy. (CSS)

REVIEW OF SYSTEMS:FMSMusculoskeletal:Back painAlwaysNeck painAlwaysArthralgias80%Myalgias80%

Fibromyalgia pain must be AXIAL not peripheral.Fibromyalgia pain must be in ALL 4 QUADRANTS, NOT unilateral, NOT upper or lower.

REVIEW OF SYSTEMS:FMSSkin:RashButterfly/malar rashr/o LupusPsoriasis/psoriatic Arth.Dry Skinr/o Thyroid DzLesionsr/o cancer

REVIEW OF SYSTEMS:FMSPsychiatric:DepressionHighly coexistantAnxietyHighly coexistantInsomniaHighly coexistantBipolar disorderHighly coexistant

With FMS,1st degree relatives of FMS patients are twice as likely to have a mood disorder.1st degree relatives of FMS patients has an 8 fold risk of FMS or other CSSs.

REVIEW OF SYSTEMS:FMSNeurological:Headache53%Paresthesias35%RLS15%CVASeizures

REVIEW OF SYSTEMS:FMSEndocrine:DiabetesAlways r/o

Thyroid DiseaseAlways r/o

Dyslipidemia? Statins

Vasomotor Perimenopausal Symptoms

REVIEW OF SYSTEMS:FMSHemo/Lymph/Immun:Easy bruising/bleedingr/o cancer

Lymphadenopathy r/o cancerinfection

REVIEW OF SYSTEMS:FMSGYN:Vag d/cr/o infectionBleedingPelvic Painr/o pregnancy

Other CSSs are Chronic Pelvic Pain, Post C-Section Neuropathy, Post Inguinal Repair Neuropathy. Remember, damaged nerves can lead to a wind-up phenomenum. What is #1 cause of abd. Pain?

O - OBJECTIVEPHYSICAL EXAM:FMS

Vital signs:Weight:200Height62BMI37B/P138/88HR92RR16Temp98.2?fever

PHYSICAL EXAM:FMSAlert & oriented x3ConfusedFibro fog 20% Memory Attn. Span Task SwitchingCleanDepressed with FMS & Chronic PainAnxious Correlation

PHYSICAL EXAM:FMSEyes:Conjunctivar/o inflammatory Dzr/o anemiaPERRLAr/o MS

EMOIr/o neuro problems

ENT:r/o infection

PHYSICAL EXAM:FMSNeck:SuppleLADr/o infectionr/o cancerThyroidr/o thyroid dz

A GOOD TIME TO CHECK TENDERPOINTS SINCE MOST ARE AROUND THE NECK

Bruits

PHYSICAL EXAM:FMSRespiratory:CTABr/o infectionEffort normalRetractionsWheezingCrackles

A GOOD TIME TO CHECK TENDERPOINTS AROUND THE BACK

PHYSICAL EXAM:FMSCV:r/o fatigue cause

ABD: r/o infection

GU:r/o infectionGYN: r/o infectionRECTAL:(not a fibromyalgia tenderpoint)

PHYSICAL EXAM:FMSLymph:Cervicalr/o infection & cancerSupraclavicularAxillaryInguinal

A GOOD OPPORTUNITY TO CHECK TENDERPOINTS WITHOUT BEING TOO OBVIOUS

PHYSICAL EXAM:FMSNeuro:MotorWeakness /?MS

Sensoryr/o cervical, lumbarspinal stenosisReflexesr/o hypo/hyperthyroid

Gaitr/o MS, NPH, Parkinsn

PHYSICAL EXAM:FMSMusculo-skeletal:FROM JointsCheck joints for RA/OACheck tenderpoints

Swelling

Erythema

Laxity

PHYSICAL EXAM:FMSSkin:Abnormal lesionsFaceTrunkExtremities

Rule out infection, lupus, psoriasis(psoriatic arthritis)scleroderma, and other skin manifestations of other rheumatologic diseases that could cause FMS like pain.

Location of FMS tender points:

Attachment of neck muscles at the base of the skull Midway between neck and shoulder Muscle over upper inner shoulder blade 2 cms below side bone at elbow upper outer buttock Hip bone Just above knee on inside Lower neck in front Edge of upper breast bone

DEMONSTRATION OF PHYSICAL EXAM WITH EMPHESIS ON FIBROMYALGIA TENDER POINTS

NEED 11 OF 18 POSITIVE TENDER POINT FOR DIAGNOSIS OF FIBROMYANGIA

FMS affects 2-3% of the general population of the US, 4% of the female population.

The female to male treatment seeking ratio is 9:1

There is a 3 fold healthcare cost in FMS compared to an average American.

SO, WHATS YOUR DIAGNOSIS SO FAR?1. Family Hx of Central Sensitization Syndrome and Psychiatric conditions2. She has an environmental trigger: MVA with friend killed3. She has non-restorative sleep

4. She has a positive physical exam: 14/18 tender points

MAYBE SHE HAS FIBROMYALGIA !

WHAT ARE YOUR DIFFERENTIAL DIAGNOSES?Hormone imbalance: Hypothyroid, menstrual irregularities, adrenal insufficiency, DM 2Infection: Post infectious fatigue (Mono), Chronic infection, Lyme Disease, HIVAutoimmune D/O: Lupus, RA, PMR, Irritable Bowel DiseaseNeurologic: Myasthenia Gravis, Multiple SclerosisPsychiatric Illnesses: Bipolar D/O, Substance abuse, eating d/o with malnutritionMalignanciesHypercalcemia (groans, stones, or bones)

What diagnostic test do you need base on your DIAGNOSIS and DIFFERENTIAL DIAGNOSIS?

Remember, FMS is a SYNDROME, a diagnosis of EXCLUSION.

DIAG. TESTSRULING OUT

U/AKidney dz, DM, InfectionCBCInfection, anemia, Fe, CancerPregnancyChem ProDM, Lyte Imbal., Hypercalcemia, ANALupusESRPolymyalgia Rheumatica (PMR)RFRheumatoid ArthritisCRPInflammationTSHHypothyroidismCPKPolymyositis, Muscle Damage

A - ASSESSMENTDiagnosis: FIBROMYALGIA - Has become the #1 pain syndrome in the US.GADDepressionInsomniah/o neck/back injury(ALL CONTRIBUTORY)ObesityTobacco abuse

P PLAN

3 Major Goals in the treatment of Fibromyalgia

What are the 3 things you need to address and treat in anyone with any chronic pain?

P PLAN



A. TREAT PAIN

P PLAN



A. TREAT PAINB. TREAT DEPRESSION

P PLAN



A. TREAT PAINB. TREAT DEPRESSIONC. TREAT INSOMNIA

P PLAN

THE TREATMENTOF FIBROMYALGIA INVOLVES:

A. Treating Fibromyalgia Pain

B. Treating Anxiety and Depression

C. Improve Sleep Architecture

P PLAN





A. TREATING FIBROMYALGIA PAINDo you treat all pain the same?Chest wall pain-NSAIDsRib fracture-NarcoticsGout-Steroids, NSAIDsMigraine-TriptansPost-op pain-NarcoticsDPN/PHN-Antiepil., SNRIs,TCAsOr, you can shoot a fly with a shotgun and give them Lortab. NPs are more sophisticated that that.(5 min. to prescribe narcotics, 30 min. to explain and treat without narcotics.)

3 TYPES OF PAIN1. Peripheral Pain (Nociceptive):Rib Fx, OA/RA, Gout, Trauma, Post-op2. Neuropathic (Damaged/entrapped nerves):DPN, PHN3. Central Pain (Non-Nociceptive):FMS, IBS, Ch. Pelvic Pain, other CSSs

Can someone with RA, DPN, and drop a brick on their foot AND have Fibromyalgia at the same time?

A. TREATING FIBROMYALGIA PAINBecause we now know more about the pathophysiology of Fibromyalgia pain, we will target our approach:

1. Target ASCENDING pain pathways

2. Target inhibitory, DESCENDING pathways

Pain pathways are a two-way street.

There are AFFERENT, conducting inward, ascending pain pathways,

(Pain towards the brain) or (Pain on a train trying to gain toward the brain)

ANDAmeliorating, inhibitory, descending pain pathways.

(Drain the pain from the brain) or(Train the pain to wane)

A. TREATING FIBROMYALGIA PAIN1. Target ASCENDING pain pathways. HOW?

Decrease spinal neuron hyperexcitability with anticonvulsantsa. -2- (alpha-2-delta) ligand anticonvulsants1. Pregabalin (Lyrica) FDA approved for Fibromyalgia2. Gabapentin (Neurontin)b. Other anticonvulsant/antiepileptic drugs

How does pregabalin (Lyrica) and gabapentin work?They bind to the -2- protein on the neuron that has voltage gated channels. A calcium ion has to go back through the gate before certain neurotransmitters can be released from the neuron.

How does Pregabalin (Lyrica) and gabapentin work?(continued)If you decrease the influx of the calcium ions, you decrease the release of certain neurotransmitters into the synaptic gap, therefore decreasing the hyperexcitability of the neuron (seizure control) and, in this case, reduce the level of Substance P and Glutamate that play a role in pain processing and decrease the wind-up phenomenum in the pain sensing neurons.

A. TREATING FIBROMYALGIA PAIN2. Target inhibitory, DESCENDING pain pathways. HOW?a. Raise Serotonin-Norepinephrine levels

1. Serotonin-Norepinephrine Reuptake Inhibitorsa. Venlafaxine (Effexor), Desvenlafaxine (Pristiq)b. Duloxatine (Cymbalta) FDA approved for FMSc. Milnacipran (Savella) FDA approved for FMS, inhibits Norepinephrine reuptake with a 3 fold higher potency that serotonin.


2. Tricyclic Antidepressants (TCAs)a. Amitriptylline (Elavil)b. Nortriptylline (Pamelor)c. Imipramined. Others


3. Muscle Relaxersa. Cyclobenzeprine (Flexeril)


4. Tramadol (Ultram, Ultram ER, Ultracet) Has SNRI properties as well as weak (mu) opioid-receptor agonist properties

5. Exercise Endorphins are pain inhibitors


HOW DO SNRIs WORK?Mechanism of action is unknown

DESCENDING PAIN CIRCUITSHypothalamus Periaquaductal Gray Rostral DorsolateralVentral PontineMedulla Tegmentum(serotonergic pathway) (noradrenergic pathway) Dorsolateral Funiculus(SNRIs put the Fun in the Funiculus)

A. TREATING FIBROMYALGIA PAIN2. Target inhibitory, DESCENDING pain pathways. HOW?a. Raise Serotonin-Norepinephrine levelsHOW?

If you can reduce the re-uptake of these neurotransmitters back into the neuron, it leaves more neurotransmitter in the synaptic gap leading to pain inhibition, same as with the antidepressant/antianxiety effect of SNRIs.

Pain pathways run through parts of the brain that tell us where the pain is and the intensity of the pain BUT,

Some of the pain pathways run through the areas of the brain such as the amygdala that are related to the affective domain or the emotional response to pain.

This leads us to the second aspect of the treatment of FIBROMYALGIA PAIN.

P PLAN





B. TREAT ANXIETY AND DEPRESSION1. Raise Serotonin-Norepinephrine levelsa. SNRIs1. Venlafaxine (Effexor) Cheaper, generic2. Duloxatine (Cymbalta) FDA approved for FMS and anxiety and depression3. Milnacipran (Savella) FDA approved for FMS, inhibits Norepinephrine reuptake with a 3 fold higher potency that serotonin. You need the serotonin reuptake inhibition to treat anxiety.

B. TREAT ANXIETY AND DEPRESSION1. Raise Serotonin-Norepinephrine levels

b. Tricyclic Antidepressants (TCAs)

Remember: TCAs are too anticholenergic and sedation at high enough doses to treat anxiety and depression

B. TREAT ANXIETY AND DEPRESSION1. Raise Serotonin-Norepinephrine levels2. Anti-Epileptic Drugsa. Pregabalin (Lyrica) FDA approved for FMS, Seizure d/o,PHN, DPN, and in Europe approved for anxiety.b. Gabapentin (Neurontin)

c. Valproaic Acid (Depakote)d. Carbamazepine (Tregretol) both used for years for mood disorders

B. TREAT ANXIETY AND DEPRESSION3. What NOT to use:a. Benzodiazepines They increase depression and increase pain scores.b. Narcotics Kills a fly with a shotgun.Morpheus the Greek god of dreams

The Goal of Treating FMS: ECONOMIC 101Try to get the pain scores from 6-7/10 to 2-3/10 so they can return to work so they can pay taxes. People addicted to benzos and narcotics tend to take more taxes than they pay in as a rule.

P PLAN





C. IMPROVE SLEEP ARCHITECTURE

80% of FMS patients report Non-Restorative Sleep.

Why do we want to improve sleep architecture?

C. IMPROVE SLEEP ARCHITECTUREFMS polysomnographic studies show abnormalities in sleep continuity as well as sleep architecture.a. Decreased REM sleep with FMSb. Increased awakenings with FMSc. Abnormal alpha wave intrusions in non-REM which is found to worsen pain in sleep with FMSd. Stage 4 or Delta wave sleep is where many restorative hormones are activated like Growth Hormone. This leads to the fibrositis symptom complex causing non-restorative sleep.

IMPROVE SLEEP ARCHITECTURE

So, poor sleep increases pain and fibrositis symptoms.

That is why Fibromyalgia is thought to be an illness of the NEURO-ENDOCRINE SYSTEM.


1. Antiepileptic Drugs Improve pain and sleepa. Pregabalin (Lyrica)1. Has a sedative effect2. Enhances slow wave delta sleepb. Gabapentin (neurontin)


2. Tricyclic Antidepressants (TCAs) Improve pain, depression and sleep.a. Amitriptylline (Elavil)b. Imipramine (Tofranil)c. Many others


3. Non-Benzodiazepine Sedatives Improve sleep.a. Zolpidem (Ambien)b. Zaleplon (Sonata)c. Eszopiclone (Lunesta)d. DO NOT use benzos

4. Teach sleep hygiene5. Treat depression and anxiety6. Exercising/Stretching not within 3 hours of HS

Which of the FDA approved medications would you want to start first?

FMS pain with Fatigue dominant: Savella

FMS pain with Depression dominant: Cymbalta

FMS pain with Insomnia dominant: Lyrica

P PLAN




CImprove Sleep Architecture

D. Other Nurse Practitioner Treatments

D. Other Nurse Practitioner Treatments (that other healthcare providers probably wont do)

Patient Education Explain itInstill a sense of self-worthAvoid disability and narcoticsEstablish anxiety reducing measuresPrayerExercise

D. Other Nurse Practitioner Treatments

5. Exercising and stretching Staying active6. Address underlying psycho-social issues and stressors , Cognitive Behavioral Therapy (CBT) referral.7. Medications8. Referral Physical Therapy, Rheumatologist, Neurologist, Pain Management9. Hugs

-2- (alpha-2-delta) ligand anticonvulsants

Adverse Reactions: Dizziness, somnolence, edema, weight gain

Interactions: Potentiates other CNS drugs

Precautions: Never stop AEDs abruptly

Serotonin-Norepinephrine Reuptake Inhibitors

Adverse Reactions: Nausea, somnolence/insomnia, constipation, dry mouth, hyperhydrosis, HTN

Interactions: Other psych meds (MAOI, SSRI, Haldol)

Precautions: Hypertension, Mania/Bipolar, Suicidal Ideation

Tricyclic Antidepressants (TCAs)

Adverse reactions: Drowsiness, anticholinergic effects, Prolonged Q-T

Interactions: Anticholinergics , Prozac, MAOIs, Alcohol/CNS depressants

Precautions: SEIZURES, Hx of seizures, Increase fall risk and arrhythmias in Elderly, Urinary retention

Tramadol (Ultra, Ultram ER, Ultracet, Ryzolt)

Adverse Reactions: Dizziness, GI upset, Constipation, SEIZURES

Interactions: MAOI, Carbamazepine, Alcohol

Precautions: SEIZURES, concomitant use with opioids

Non-benzo Hypnotics

Adverse Reactions: CNS effects, Complex sleep related behaviors

Interactions: Alcohol, CNS depressants (Marilyn Monroe effect)Precautions: Depression, Behavioral changes

BIG PICTURE PRECAUTIONS

SEIZURES: Tricyclic Antidepressants (TCAs), Tramadol, and bupropion (Welbutrin) lower the seizure threshold in people who may have never had a seizure. Caution using together.

SEROTONIN SYNDROME: Keep in mind the doses of concomitant use of traditional SNRIs and other medications with SNRI effect like TCAs and Tramadol. No need to add an SSRI.

QUESTIONS?