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Page 1: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Sleep Disturbances in

Fibromyalgia Patients

Robert Bennett MD, FRCP, MACR

Page 2: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Disclosure

Research support : Forest, Jazz, Pfizer

Advisory Boards: Lilly, Jazz

Speaker Bureaus: None

Page 3: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

3 Key References

1) Rosenthal MS, Physiology and neurochemistry of sleep. Am. J. Pharm. Educ., 62, 204-208, 1998

2) Passarella S et al. Diagnosis and treatment of insomnia. Am J Health-Syst Pharm. 2008; 65:927-34

3) Moldofsky H. Rheumatic manifestations of sleep disorders. Curr Opin Rheumatol 2010;22(1):59-63

Page 4: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Objectives

Page 5: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Page 6: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

      

      

        

              

      

        

              

THE PRINCIPLES AND

PRACTICE OF MEDICINE

DESIGNED FOR THE USE OF PRACTITIONERS AND STUDENTS OF MEDICINE

BY WILLIAM OSLER, M. D.

FELLOW OF THE ROYAL COLLAGE OF PHYSICIANS, LONDON PROFESSOR OF MEDICINE IN THE JOHNS HOPKINS UNIVERSITY AND PHYSICIAN-IN-CHIEF TO THE JOHNS HOPKINS HOSPITAL, BALTIMORE FORMERLY

PROFESSOR OF THE INSTITUTES OF MEDICINE MOOILL UNIVERSITY, MONTREAL AND PROFESSOR OF OLINIOAL MEDICINE 1H THE UNIVERSITY CF PENNSYLVANIA PHILADELPHIA

NEW YORK D. APPLETON AND

COMPANY 1892

William Osler

1849 - 1919

Page 7: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

The Principles and Practice of MedicineWilliam Osler MD, 1892

“Neurasthenia”: a condition of weakness or exhaustion of the nervous system

1. Sleeplessness is a frequent concomitant2. The majority are moody or depressed3. They have weariness on the least exertion4. The aching pain in the back of the neck is the most constant complaint5. There are spots of local tenderness in the spine

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Alpha-deltasleep

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First “Scientific” Study in FM

Delta (≈1cps)

Alpha + delta

Auditory stimulation in a healthy control

Moldofsky et al. Psychosomatic Med. 37:341-351, 1975

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Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

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A. REM sleep

B. Non-REM sleep Stage 1 - Transition from wake to sleep Stage 2 – Largest percentage of sleep Stages 3 and 4 – Restorative sleep

There are 4 to 5 cycles of REM and non-REM sleep each night

Each cycle lasts 1.5 to 2 hours

Sleep stages

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Sleep stages

REMStage 1Stage 2Stage 3Stage 4

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Polysomnography

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PolysomnographyPolysomnographic data is reviewed in 30 second "epochs"

Sleep latency Sleep efficiency Percent time in REM and non-REM sleep Percent time in each of the 4 sleep stages Electro-oculogram (EOG) EMG chin EMG tibialis anterior Nasal air flow Chest and abdominal movements Oxygen saturation ECG

The number of minutes of sleep divided by the number of minutes in bed. Normal is approximately 85 to 90% or higher.

Iber, C et al. The AASM Manual for the Scoring of Sleep: American Academy of Sleep Medicine, Westchester, IL 2007

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Sleep architecture

Decreasing frequency

Increasing amplitude

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Drowsy EEG

During the earliest phases of sleep, when people are drowsy the brain produces beta waves (13–35 Hz). As the brain begins to relax slower alpha waves (8–12 Hz) are produced. During this time when you are not quite asleep, people may experience vivid sensations known as hypnagogic hallucinations. Another very common event is myoclonic jerks.

Beta waves (12-30 HZ)

Eyes openEyes closed

Alpha waves (8 – 12 HZ)EEG leads

Chin EMG

EOG

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Stage 1 sleep

Slow rolling eye movements

Theta waves (4–7.5 Hz) with some alpha

Chin EMG

EOG

EEG leads

Stage 1 is a transition period between wakefulness and sleep. In Stage 1, the brain produces high amplitude theta waves (4–7 Hz), which are very slow brain waves. This period of sleep lasts only 5-10 minutes. If you awaken someone during this stage, they might report that they weren't really asleep.

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Stage 2 sleep

Stage 2 lasts for approximately 20 minutes, mainly theta waves (4–7 Hz). Then the brain begins to produce bursts of rapid, rhythmic brain wave activity known as sleep spindles and K-complexes. Body temperature starts to decrease and heart rate begins to slow.

Minimal eye movement

Minimal chin EMG

Theta waves (4–7 Hz)

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Stages 3 and 4 of non-REM sleep

Predominant delta waves (0.5–3.5 Hz)

Stages 3 and 4 are often referred to as delta sleep because slow brain waves known as delta waves (0.1 – 4 Hz) occur during this time. Stages 3/4 are a deep sleep that lasts for approximately 30 minutes. Bed-wetting, night terrors and sleepwalking are most likely to occur at the end of stage 4 sleep. It is followed by REM sleep.

Some eye movement

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REM sleep

Starts after loss of chin EMG

Rapid eye movements

Bursts of alpha activity

Rapid eye movement (REM) sleep is characterized by eye movement, increased respiration rate and increased brain activity. . Vivid dreams often occur in this sleep stage. Dreaming occurs is due to increased brain activity, but voluntary muscles become paralyzed.

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Sleep control mechanismsEncephalitis lethargica

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1. A somnolent-opthalmoplegic form with profound sleepiness often leading to coma and death, paralysis of cranial nerves and expressionless faces.

2. A hyperkinetic form with restlessness, twitching of muscles, anxiety and severe insomnia.

3. An akinetic form with muscle weakness, rigidity, and severe insomnia (postencephalitic parkinsonism).

An epidemic that spread throughout the world from 1977 to 1928.

Sleep control mechanismsEncephalitis lethargica

Postulated cause is a mutation of the H1N1 influenza virus

? N-methyl-D-aspartate (NMDA) receptor antibody mediated

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Sleep control mechanisms

Constantin von Economo1876 - 1931

Von Economo, reported that encephalitis lethargica was due to injury to the posterior hypothalamus and rostral midbrain.

He recognized that one group of individuals infected during the same epidemic instead had the opposite problem: a prolonged state of insomnia that occurred with lesions of the pre-optic area and basal forebrain.

He hypothesized that lesions of the posterior hypothalamus could cause the disease we now call narcolepsy.

Based on his observations, von Economo predicted that the region of the hypothalamus near the optic chiasma would contain sleep-promoting neurons, whereas the posterior hypothalamus would contain neurons that promote wakefulness.

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Sleep control mechanismsOrexin neuronal projectins

Orexin neurons originating in the posterior hypothalamus regulate sleep and wakefulness by sending excitatory projections to the entire CNS, with particularly dense projections to monoaminergic and cholinergic nuclei in the brain stem.

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SleepAwake

Sleep control mechanisms

VLPO = ventrolateral pre-optic nucleus (GABA & galanin)ORX = orexin nucleus (orexins)LC = locus ceruleus (nor-adrenaline)Raphe = raphe magnus (serotonin)TMN = tubermammilary nucleus (histamine)

Page 26: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

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DSM-IV criteria for primary insomnia:

1) A complaint of difficulty falling asleep, staying

asleep or non-restorative sleep

2) Duration of ≥1 month

3) Causes clinically significant distress or impairment

4) Does not occur exclusively during the course of a

mental disorder

5) Is not due to another medical or sleep disorder or

effects of medications/substance abuse

Insomnia – definition

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Riemann et al. Pharmacopsychiatry. 2011 Jan;44(1):1-14.

Insomnia - consequences

1) Fatigue / malaise

2) Impaired attention, concentration, memory

3) Vocational dysfunction

4) Daytime sleepiness

5) Motivation / energy / initiative reduction

6) Proneness for errors / accidents at work or while driving

7) Tension headache

8) Obesity / diabetes

9) Hypertension

10) Depression / anxiety

11) Coronary heart disease

12) Increased mortality

Sleep loss may transiently improve depression

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Hyperarousal Sleep disturbance

Neurobiologicalalterations

Dysfunctional behavior

Stressors

Long-termconsequences

Insomnia – mechanisms

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Am J Psychiatry 2004; 161:2126–2129

Insomnia – mechanisms

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(A) Patients with insomnia: brain areas where metabolism was not decreased in waking and sleep states

(B) Healthy subjects: brain areas where metabolism, while awake, was higher than in patients with insomnia

Insomnia – mechanisms

Interacting neural networks are involved in the neurobiology of insomnia:

1. General arousal system (ascending reticular formation and hypothalamus), 2. Emotion-regulating system (hippocampus, amygdala, and anterior cingulate cortex), 3. Cognitive system (prefrontal cortex)

Page 32: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Page 33: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Sleep disturbances in FM

Insomnia α intrusion rhythm cyclic alternating rhythm (CAP)

Periodic limb movements (PLM/RLS) Snoring and arousals Apnea and hypopnea Periodic breathing Bruxism

Page 34: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

First “Scientific” Study in FM (1975)

Delta (≈1cps)

Alpha + delta

Moldofsky et al. Psychosomatic Med. 37:341-351, 1975

Auditory stimulation in

healthy controls

Page 35: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

ECG

R. leg

L. leg

Chin EMG

EEG leadsNormal sleep

α-EEG sleep

Alpha – delta sleep

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Cyclic alternating pattern (CAP) in FM

J Rheumatol 2004; 31:1193–9

Cyclic Alternating Pattern: A New Marker of Sleep Alteration in Patients with Fibromyalgia?

Maurizio Rizzi, Piercarlo Sarzi-puttini, Fabiola Atzeni, Franco Capsoni, Arnaldo Andreoli, Marica Pecis, Stefano Colombo, Mario Carrabba, Margherita Sergi

Found CAP pattern in 68% FM patients vs 45% controls.

Hypothesized that CAP in FM maybe a result of chronic pain reducing sleep efficiency, causing more CAP and more arousals and increasing the occurrence of periodic breathing.

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Cyclic alterating pattern in FM

Sergi et al. Eur Resp J 1999; 14:203-208

R. EOG

L. EOG

EEG

EEG

Air flux

Thorax

EMG

Abdomen

%O2 sat.

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Upper airway resistance syndrome

The upper airway resistance syndrome (UARS) is a form of sleep-disordered breathing in which repetitive increases in resistance to airflow within the upper airway lead to brief arousals and daytime somnolence. Patients do not meet criteria for obstructive sleep apnea.Manometry and pneumotachographic are the "gold standard" for diagnosis.

Sleep 2004 May 1;27(3):459-66

Now considered to be same as “cyclic alterating rhythm”

Page 39: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Periodic leg movements (PML)

• PLM is a repetitive cramping or jerking of the legs during  sleep; it can range from a small movements in the ankles and toes, to wild flailing of all 4 limbs

• PLM is the 4th leading cause of insomnia

• PLM affects about 5% of total population

• More common in women (~20% of females age ≥ 50)

• PLM affects about 60% of all FM patients

Natarajan R. Review of periodic limb movement and restless leg syndrome. J Postgrad Med 2010;56:157-6

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Restless legs syndromeJ Clin Sleep Med 2010;6(5):423-427

RLS symptomsFM patients = 33%Healthy controls = 3.1%

Conclusions:

There is a high prevalence and odds of having RLS in FM patients.

Clinicians should routinely query FM patients regarding RLS symptoms becausetreatment of RLS can potentially improve sleep and quality of life in these patients.

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RLS associations

Hereditary (~50%)

Uremia (~50%)

Narcolepsy (~50%)

Pregnancy (~20%)

Diabetes

REM sleep behavioral disorder

Parkinson’s disease

Hypothyroidism

Iron deficiency (ferritin ≤ 50 ng/ml)

Some drugs

(TCAs, SSRIs, DA, L-thyroxine, tramadol, benadryl)

Opioid / benzodiazapine withdrawal

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Sleep apnea

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Sleep apneaExcessive daytime sleepiness

*Epworth score usually ≥ 15

Loud snoring - more prominent in obstructive sleep apnea

Abrupt awakenings with shortness of breath

– more prominent in central sleep apneaObserved episodes of apnea during sleepAwakening with a dry mouth or sore throatMorning headacheDifficulty losing weightHypertension, gastric reflux, arrythmias

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Obstructive sleep apnea

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Central sleep apnea

Central

Page 46: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Page 47: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

SITUATION Score

1. Sitting and reading

2. Watching TV

3. Sitting inactive in a public place

4. As a passenger in a car for an hour

5. Lying down to rest in the afternoon

6. Sitting and talking to someone

7. Sitting quietly after a lunch without alcohol

8. In a car, while stopped for a few minutes in traffic

How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? 

0 = no chance, 1= slight chance2 = moderate chance 3 = high chance

Epworth sleepiness scale(http://epworthsleepinessscale.com)

ANALYSIS

Score of 1-6 getting enough sleep

Score of 4-8 the average score

Score of 9-15 very sleepy and need further evaluation

Score of ≥16 dangerously sleepy and urgently need

specialist evaluation/polysomnogram

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(1) Do you have uncomfortable feelings or sensations in the legs (or urge to move the legs) while sitting or lying down?

(2) Is the discomfort was worse when resting?

(3) Is the discomfort improved or resolved with walking?

(4) Is the discomfort worse in the evening or nighttime?

Restless legs questionnaire

Hening WA et al. The Johns Hopkins diagnostic interview for the restless legs syndrome. Sleep Med 2003;4:137-41

Crawling TinglingCramping CreepingPulling PainfulElectric ItchyGnawing Aching

Score of 4 provides 90% diagnostic sensitivity

Page 49: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

* A diagnosis of PLMS requires 3 periods of ≥30 movements followed by partial arousal or awakening

Periodic limb movement disorder (PLMD)(nocturnal myoclonus)

1) Patient has RLS

2) Report from sleep partner

3) Polysomnogram

4) Response to dopamine agonist

*

Diagnostic considerations:

80% of RLS patients have periodic limb movement disorder (PLMD)

Paradoxically only 30% PLMD patients have RLS

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Polysomnography

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SLEEP 2003;26(6):754-60

SLEEP 2003;26(6):754-60

Polysomnography is indicated when a sleep-related breathing disorder or periodic limb movement disorder is suspected, initial diagnosis is uncertain, treatment fails, or precipitous arousals occur with violent or injurious behavior.

Polysomnography is not indicated for the routine evaluation of transient insomnia, chronic insomnia, insomnia associated with psychiatric disorders or insomnia associated with fibromyalgia or chronic fatigue syndrome.

Page 52: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Page 53: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

ChronicPain

Disturbedsleep

Chicken or Egg?

Dysfunctional sleep and pain

?

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Clin J Pain Volume 27, Number 5, June 2011

A night of poor sleep was followed by increased pain ratings the following day and a day of increased pain was followed by a night of poor sleep.

Dysfunctional sleep and pain

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SLEEP 2007;30(4):494-505

Dysfunctional sleep and pain

MEASUREMENTS:

Nocturnal Polysomnography (PSG)

Wrist Actigraphy

Sleep and Pain Diaries

Diffuse Noxious Inhibitory Controls (DNIC)

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Dysfunctional sleep and pain

FA underwent 8 forced awakenings (one per hour) on nights 3-5.

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Impaired sleep is associated with reduced activation of the inhibitory pain pathway

Bottom line:

Frequent sleep disruptions cause a reduction in the descending inhibitory

control system for pain

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ChronicPain

Disturbedsleep

Dysfunctional sleep and pain

?

Page 59: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Sleep improvement reduces pain

Spaeth et al. Annals of the Rheumatic Diseases (in press)

FIQ sleep vs pain VAS (r=0.7, p<0∙001)

Page 60: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Objectives

1) Historical aspects of sleep in FM

2) Physiology of sleep

3) Insomnia

4) Disturbed sleep in FM patients

5) Evaluation of disturbed sleep in FM

6) Disturbed sleep and pain

7) Management

Page 61: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Management of FM associated sleep disorders

1) Explore sleep hygiene and behavioral issues

2) Look for an associated primary sleep disorder:

RLS/PLM, sleep apnea, UARS, bruxism

3) Review current medications for sleep side effects

4) Review all previous treatments

5) Assess for nocturnal pain generators

6) Screen for depression and anxiety

Modified from Abad VC et al. Sleep Med ReV 2008;12:211-228

CrampsCarpal tunnelBursitisSpinal OASpinal stenosisOA hip or knee

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Comment:Young and middle-age patients with sleep-onset insomnia can often derive significantly greater benefit from CBT than pharmacotherapy. CBT should be considered a first line intervention for chronic insomnia.

JAMA. 2001;285:1856-1864

CBT for insomnia

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Basic principles of CBT

Sleep hygiene

Stimulus control

Sleep restriction

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1) Maintain a regular sleep schedule2) Sleep as long as necessary to feel rested (usually 7 to

8 hours for adults) and then get out of bed3) Adjust the bedroom environment to decrease stimuli

(light, sound, temperature)4) Try not to force sleep (see “sleep restriction”)5) Resolve concerns or worries before bedtime6) Avoid caffeinated beverages after lunch7) Avoid alcohol and tobacco in late afternoon and

evening8) Exercise regularly, preferably more than 4 hours prior

to bedtime9) Avoid daytime naps that are longer than 20 to 30

minutes or occur late in the day

Sleep hygiene

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Rationale: Patients with insomnia often associate their bed and bedroom with the fear of not sleeping. The longer they stay in bed the stronger the association becomes.

Stimulus control

1) Patients should not go to bed until they are sleepy2) Set an alarm clock to wake them at the same time

every morning, including weekends.3) They should not engage in activities that reward them

for being awake, such as eating or watching TV.4) They should not spend more than 20 minutes in bed

awake.5) If they are awake after 20 minutes, they should leave

the bedroom and engage in a relaxing activity.6) They should not return to bed until they feel tired.7) If they return to bed and still cannot sleep within 20

minutes, the process should be repeated.

Page 66: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

Rationale:  Many patients with insomnia stay in bed trying to get to sleep. Sleep restriction therapy increases the drive to sleep by limiting the total time allowed in bed.

Sleep restriction therapy

1) Decrease the time spent in bed to equal the time that the patient reports sleeping (but not less than 5 hours per night)

2) The patient reports the amount of sleep obtained the previous night and the amount of time spent in bed.

3) The clinician then computes the sleep efficiency (reported time asleep divided by the reported time in bed).

4) The time in bed is increased by 15 to 30 minutes once the sleep efficiency exceeds 85 percent.

5) This process is repeated until the patient reports improved sleep without residual daytime sleepiness.

Spielman et al. Insomnia: Sleep restriction therapy. Insomnia Diagnosis and Treatment, Informa UK Ltd, London 2010. p.277.

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Drug Action Dose (mg) Half-life (h)

Estazolam 1 BzRA 1–2 10–24Flurazepam 1 BzRA 15–30 48–120Temazepam 1 BzRA 15–30 8–20Triazolam 1 BzRA 0.125–0.25 2.4Quazepam 1 BzRA 7.5–15 48–120Zolpidem 2 BzRA 5–10 1.4–3.8Zolpidem ER 2 BzRA 6.25–12.5 2.8Zaleplon 2 BzRA 5–20 1.0Eszopiclone 2 BzRA 1–3 6.0Ramelteon 3 MtRa 8 1–2.6

Type 1 indicates benzodiazepines, type 2 indicatesnon-benzodiazepines, and type 3 indicates melatonin.

FDA approved drugs for the treatment of insomniaSleep onset insomnia use a short-acting

medication:Zolpidem Capelin TriazolamLorazepam Ramelteon

Sleep maintenance insomnia use a longer-acting medication :Low dose doxepinZolpidem ER EszopliconeTemazepam Estazolam From: UpToDate 2011

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Slow wave sleep enhancers

GABA reuptake inhibitor: Tiagabine

GABA enhancer:Sodium oxybate (not approved for FM)

Selective GABAA agonistGaboxadol (not available in USA)

VDCC α2δ calcium channel modulators:Gabapentin/pregabalin

5-HT[2A] receptor antagonist:Ritanserin, ketanserin (not available in USA)

GGABA rec. subunits

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Onset Duration REM SWS

Benzodiazapines ↑ ↑ ↔ ↓Benzo. Receptor ↑ ↑ ↔  ↔Anti-histamines (old) ↑ ↑ ↓↓  ↑Anti-histamines (newer) ↔ ↔ ↔ ↔Anti-epileptics (old) ↑ ↑ ↓ ↑Anti-epileptics (newer) ↑ ↑ ↔ ↑TCAs and SARIs ↑ ↑ ↔ ↔SSRIs and SNRIs ↓ ↓  ↔ ↔Ramelteon ↑ ↑ ↔ ↔Sodium oxybate ↑ ↑ ↔ ↑Tiagabine ↑ ↑ ↔ ↑Psychostimulants ↓ ↓ ↓ ↓β adrenergic blockers ↔ ↓ ↓ ↔α adrenergic blockers ↔ ↓ ↓ ↔Corticosteroids ↔ ↓ ↓ ↔

Drugs and sleep architecture

Page 70: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

J Rheumatol. Epub Sep 2, 2011

An 8 week study of cyclobenzaprine (1–4 mg hs) in 37 FM subjects and 36 controls.

Subjects had to have the α-EEG sleep anomaly in ≥40% epochs of non-REM sleep

Low dose cyclobenzaprine

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% Change

Cyclobenz.

% Change

PlaceboP-value

Pain - 26.1 0.00 0.04*

Fatigue - 14.0 + 4.30 0.13

Tenderness - 30.1 + 3.20 0.03*

HAD depression - 22.2 + 10.4 0.02*

Total sleep time + 12.3 0.00 0.10

Sleep efficiency + 15.6 + 3.6 0.09

% Stage 3 sleep + 16.2 - 2.80 0.17

% Stage 4 sleep - 28.6 + 22.9 0.03*

Low dose cyclobenzaprine

Page 72: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.

RLS / PLM management

General measures

Correct iron deficiency

Stop “aggravating” drugs

Dopamine agonists

Gabapentin, pregabalin, valproate

Clonidine

Clonazepam

Opioids

Relaxing bedtime routineRegular stretchingMinimize caffeine, alcohol, tobaccoAvoid exercise 2 h before sleep Cold compress application

CarbidopaLevodopaPramipexoleRopinirole Pergolide Cabergoline

Anti-nausea drugsOTC antihistamines Antidepressants (TCAs and SSRIs) AntipsychoticsTramadol

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Sleep apnea management

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Future Directions

1. Individualized management of insomnia

2. Widespread adoption of CBT as an initial management strategy

3. Improved non-benzodiazepines4. Development of Orexin modulators5. Newer 5-HT receptor antagonists

Page 75: Sleep Disturbances in Fibromyalgia Patients Robert Bennett MD, FRCP, MACR.