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Insomnia Pharmacotherapy A Practical Guide for Primary Care

Offices in Jacksonville, FL Fortis Spectrum is the educational partner for this session.

Session 7

Session 7: Insomnia Pharmacotherapy: A Practical Guide for Primary Care Learning Objectives

• Define 3 practice interventions that will enhance the diagnosis and treatment of insomnia. • Describe the components of an effective risk-benefit analysis leading to an insomnia treatment plan.

Faculty Paul Doghramji, MD Family Physician, Collegeville Family Practice Medical Director, Ursinus College Collegeville, Pennsylvania Paul P. Doghramji, MD, is cofounder of Brookside Family Practice & Pediatrics, a current affiliate of Pottstown Medical Specialists, in Pottstown, Pennsylvania. He has also been attending physician in family practice, chair of the Utilization Management Committee, and physician advisor at Pottstown Memorial Medical Center. Most recently he has moved his practice location to Collegeville Family Practice in Collegeville, Pennsylvania, both subsidiaries of Pottstown Medical Specialists, Inc. Dr Doghramji received his medical degree from Jefferson Medical College in Philadelphia and completed his residency in family practice at Chestnut Hill Hospital, also in Philadelphia. He is a fellow of the American Academy of Family Physicians, a member of the National Headache Foundation and Chronic Fatigue and Immune Dysfunction Syndrome Association. He has been certified by the American Board of Family Practice in 1985, and has been recertified every six years since then. Karl Doghramji, MD Professor, Jefferson Medical College Thomas Jefferson University Philadelphia, Pennsylvania Dr Doghramji is professor in the Department of Psychiatry and Human Behavior at Jefferson Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania, and director of the Sleep Disorders Center at Thomas Jefferson University Hospital, also in Philadelphia. Dr Doghramji is also chair of the Albert M. Biele, MD, Memorial Lectureship in Psychiatry in the Department of Psychiatry and Human Behavior at Jefferson Medical College. Dr Doghramji received his medical degree from Jefferson Medical College and completed his internship in internal medicine at Presbyterian–University of Pennsylvania Medical Center in Philadelphia, his residency in psychiatry at Thomas Jefferson University Hospital, and his clinical research fellowship in sleep disorders medicine and polysomnography at Montefiore Medical Center/Albert Einstein College of Medicine in the Bronx, New York. He is also an Academic Associate in the Adult Division of the Institute of the Psychoanalytic Center of Philadelphia. Faculty Financial Disclosure Statements The presenting faculty reported the following: Dr Doghramji, MD, receives honoraria and speaker fees from Takeda Pharmaceuticals North America, Inc.; sanofi-aventis U.S.; and Sepracor, Inc. Dr Doghramji receives speaker fees from GlaxoSmithKline; Boehringer Ingelheim Pharmaceuticals, Inc.; Jazz Pharmaceuticals; Takeda Pharmaceuticals North America, Inc.; sanofi-aventis U.S.; and Sepracor, Inc. He also receives consulting fees from sanofi-aventis, U.S. and owns stock in Merck & Co., Inc. Education Partner Financial Disclosure Statements The content collaborators at Fortis Spectrum have reported that they have no disclosures to report. Drug List Generic Trade estazolam Prosom flurazepam hydrochloride Dalmane quazepam Doral temazepam Restoril

Generic Trade triazolam Halcion zolpidem tartrate Ambien eszopiclone Lunesta zaleplon Sonata

Session 7

Generic Trade ramelteon Rozerem tiagabine hydrochloride Gabitril gabapentin Neurontin pregabalin Lyrica Investigational agomelatine Valdoxan indiplon epilvanserin M100907 ritanserin gaboxadol NGD96-3

Off-Label trazodone Desyrel nefazodone hydrochloride Serzone mirtazapine Remeron doxepin Adapin, Sinequan

Suggested Reading List Bootzin RR, Epsteil D. Stimulus control. In: Lichstein KL, Morin CM, eds. Treatment of Late-Life Insomnia. Thousand Oaks, CA: Sage Publications, Inc.; 2000:167-184. Crenshaw MC, Edinger JD. Slow-wave sleep and waking cognitive performance among older adults with and without insomnia complaints. Physiol Behav. 1999;66:485-492. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders: An opportunity for prevention? JAMA. 1989; 262:1479-1484. Institute of Medicine. Institute of Medicine Report on Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. April 4, 2006. Morin CM, Colecchi C, Sone J, et al. Behavioral and pharmacological therapies for late life insomnia. JAMA. 1999;281:991-999. Morin CM, Kowatch RA, Barry T, et al. Cognitive-behavior therapy for late-life insomnia. J Consult Clin Psychol. 1993;61:137-146. National Sleep Foundation. 2003 Sleep in America poll. April 2003. Available at: http://www.sleepfoundation.org/2003poll.cfm. Accessed February 9, 2004. Shochat T, Martin J, Marler M, et al. Illumination levels in nursing home patients: effects on sleep and activity rhythms. J Sleep Res. 2000;9:373-380. Walsh JK, Benca RM, Bonnet M, et al. Insomnia: assessment and management in primary care. Am Fam Physician. 1999;59:3029-3037. Zammit GK, Weiner J, Damato N, et al. Quality of life in people with insomnia. Sleep. 1999;22(suppl 2):S379-S385.

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1

1

Insomnia Insomnia Pharmacotherapy:Pharmacotherapy:

A Practical Guide for Primary CareA Practical Guide for Primary Care

2

Course Objectives:Course Objectives:

Define three practice interventions Define three practice interventions that will enhance the diagnosis and that will enhance the diagnosis and treatment of insomniatreatment of insomnia

Describe the components of an Describe the components of an effective riskeffective risk--benefit analysis leading benefit analysis leading to an insomnia treatment planto an insomnia treatment plan

3

Part I: Insomnia OverviewPart I: Insomnia Overview

4

Insomnia DefinedInsomnia Defined

Complaint of Complaint of inadequate or inadequate or insufficient sleep insufficient sleep despite adequate despite adequate opportunityopportunity

Adversely affect Adversely affect waking functionwaking function

5

Prevalence of Specific Prevalence of Specific Insomnia ComplaintsInsomnia Complaints““Sleep disruptionSleep disruption”” in general in general population ~30%population ~30%

Sustained insomnia with daytime Sustained insomnia with daytime functional impairment (= insomnia functional impairment (= insomnia diagnosis) ~10% diagnosis) ~10%

Symptoms in general practice ~50%Symptoms in general practice ~50%

National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults June 13-15, Sleep 2005 Vol. 28 6

Primary vs. Primary vs. ComorbidComorbidInsomniaInsomnia

OhayonOhayon MM. MM. Sleep Medicine RevSleep Medicine Reviewiew 2002; 6:972002; 6:97--111111

Psychiatric Disorders

44%

Primary Insomnia

16%

No DSM-IV Diagnosis

24%

Medical disorders

11%

Other Sleep Disorders

5%

2

7

Impact of Impact of ComorbidComorbid Disease Disease on Insomnia Prevalenceon Insomnia Prevalence

Insomnia prevalence is increased in:Insomnia prevalence is increased in:Major psychiatric disorders, e.g., Major psychiatric disorders, e.g., depression, anxiety, schizophreniadepression, anxiety, schizophreniaNeurological disorders, e.g., ParkinsonNeurological disorders, e.g., Parkinson’’s s disease, dementiadisease, dementiaMedical disorders, e.g., COPD, diabetesMedical disorders, e.g., COPD, diabetesPrimary sleep disorders, e.g., sleep apnea, Primary sleep disorders, e.g., sleep apnea, restless legs syndromerestless legs syndrome

Roth T. and T. Roehrs, Clinical Cornerstone 2003 5(3): 5-15 8

Insomnia in Primary CareInsomnia in Primary Care

9

Insomnia and Insomnia and ComorbidComorbidDisease: A Circular RelationshipDisease: A Circular Relationship

InsomniaInsomnia

ComorbidComorbidDiseaseDisease

10

0.00.10.20.30.40.50.60.70.80.91.0

0 5 10 15 20 25 30 35 40 45 50 55 60Estim

ated

Cum

ulat

ive

Prob

abili

ty o

f Ons

et

Days to Onset of Response

Eszopiclone 3 mgPlacebo

Treatment

Eszopiclone in Patients with Insomnia Related to Major Depressive Disorder

ESZ + FLX

PBO + FLXP=.0002

Time to Response Based on Clinical Time to Response Based on Clinical Global ImpressionGlobal Impression--Improvement ScaleImprovement Scale

Fava M et al; Biological Psychology 2006:59;1052-1060

11

Insomnia & Major Insomnia & Major Depressive DisorderDepressive Disorder

Fava M et al; Biological Psychology 2006:59;1052-1060 12

Consequences of InsomniaConsequences of Insomnia

Increased risk of psychiatric disordersIncreased risk of psychiatric disorders

Increased pain sensitivityIncreased pain sensitivity

Decreased quality of life (QOL) Decreased quality of life (QOL)

Motor vehicle and workplace accidentsMotor vehicle and workplace accidents

Falls and hip fracturesFalls and hip fractures

MortalityMortality

3

13

Part II: Insomnia TherapyPart II: Insomnia Therapy

14

Recommended Insomnia Recommended Insomnia TherapyTherapy

Behavioral therapy Behavioral therapy -- e.g., sleep hygiene, e.g., sleep hygiene, cognitive behavioral therapy (CBT)cognitive behavioral therapy (CBT)Approved pharmacological therapyApproved pharmacological therapy

Chronic insomnia is a major public health problem Chronic insomnia is a major public health problem affecting millions of individuals, along with their affecting millions of individuals, along with their families and communities.*families and communities.*

*National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults June 13-15, Sleep 2005 Vol. 28

15

Sleep Hygiene: An Essential Sleep Hygiene: An Essential Component of All Insomnia TreatmentComponent of All Insomnia Treatment

Regular sleepRegular sleep--wake cyclewake cycleRegular exercise in the Regular exercise in the morning and/or afternoonmorning and/or afternoonIncrease exposure to bright Increase exposure to bright light during the daylight during the dayMinimize exposure to bright Minimize exposure to bright light at nightlight at nightAvoid heavy meals or drinking Avoid heavy meals or drinking within 3 hours of bedtimewithin 3 hours of bedtimeEnhance sleep environment Enhance sleep environment Avoid caffeine, alcohol and Avoid caffeine, alcohol and nicotinenicotine

KupferKupfer DJ, Reynolds CF. DJ, Reynolds CF. New England Journal of MedicineNew England Journal of Medicine 1997; 336:3411997; 336:341--346346 16

Sleep Hygiene Patient ResourceSleep Hygiene Patient Resource

www.SleepFoundation.org

17

Cognitive Behavioral Therapy for Insomnia

Addresses the multiple factors that perpetuate insomnia

An Ideal CBT approach incorporates multiple modalities

Success depends on trained therapist

18

0

10

20

30

40

50

60

70

80

CBT PCT CBT+PCT

Plbo CBT PCT CBT+PCT

Plbo

Pre-Treatment Post-Treatment

Morin et al., JAMA 1999;281:991-999

WA

SO (m

in)

Sleep Diary Polysomnography

WASO = Wake after sleep onset; CBT = cognitive behavior therapy; PCT = pharmacotherapy

Efficacy of CBT

4

19

Insomnia Pharmacotherapy in Insomnia Pharmacotherapy in 20082008

NutraceuticalsNutraceuticalsOTC agentsOTC agentsOffOff--label label prescriptive prescriptive agentsagentsApproved Approved prescriptive prescriptive agentsagents

20

NutraceuticalNutraceutical TherapiesTherapies““Internet therapiesInternet therapies””No FDA oversight and No FDA oversight and fewer datafewer dataMany GABAMany GABA--ergicergicAn incomplete list:An incomplete list:

•• LavenderLavender•• German chamomileGerman chamomile•• Mimosa blossomsMimosa blossoms•• MelatoninMelatonin•• Valerian RootValerian Root•• ““Sleeping BuddhaSleeping Buddha””

National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults June 13-15, Sleep 2005 Vol. 28

21

FDA WARNS CONSUMERS AGAINST TAKING FDA WARNS CONSUMERS AGAINST TAKING DIETARY SUPPLEMENT "SLEEPING BUDDHA"DIETARY SUPPLEMENT "SLEEPING BUDDHA"

Source: http://www.fda.gov/bbs/topics/NEWS/NEW00625.html (accessed 2.28.2008)22

Most Common Rx for Most Common Rx for InsomniaInsomnia

Walsh JK. Walsh JK. SleepSleep 2004; 27:14412004; 27:1441--14421442

Occ

urre

nces

(Milli

ons) 2002 prescribing data

23

Sedating AntidepressantsSedating AntidepressantsMost commonly used agent in U.S. is Most commonly used agent in U.S. is trazodonetrazodoneNo positive efficacy data in nonNo positive efficacy data in non--depressed depressed patientspatientsCan cause Can cause daytime sedationdaytime sedationPotentially significant adverse effects raising Potentially significant adverse effects raising concerns about the riskconcerns about the risk--benefit ratiobenefit ratio

Mendelson, WB, Clinical Psychiatry 2005 66(4): 469-76


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Over the Counter Sleep Agents Over the Counter Sleep Agents (e.g., (e.g., DiphenhydramineDiphenhydramine))

KupferKupfer DJ, Reynolds CF III. DJ, Reynolds CF III. New England Journal of MedicineNew England Journal of Medicine 1997 336:3411997 336:341--346346Richardson et al., Richardson et al., Clinical PsychopharmacologyClinical Psychopharmacology 2002 22:5112002 22:511--515515

Advantages:Advantages:

Disadvantages 1,2:Disadvantages 1,2:

Prescription not neededPrescription not needed

Efficacy not consistentEfficacy not consistentLimited supporting studies on Limited supporting studies on

efficacy in treating insomniaefficacy in treating insomniaPotential for residual effectsPotential for residual effectsNo wellNo well--defined effective dosedefined effective doseRapid onset of toleranceRapid onset of tolerance

5

25

DiphenhydramineDiphenhydramine ToleranceTolerance

Richardson et al., Richardson et al., Clinical PsychopharmacologyClinical Psychopharmacology 2002 22:5112002 22:511--515515

Sleep latency = time required to fall asleepSleep latency = time required to fall asleep

26

BzRABzRA Hypnotics: Mechanism Hypnotics: Mechanism Principal CNS Principal CNS GABA receptorGABA receptorPentamerPentamerconstructed constructed from 3 types of from 3 types of subunit subunit ((αα, , ββ, and , and γγ) ) Binding sites for Binding sites for multiple multiple modulators modulators (including (including BzBz))αα subunit has 6 subunit has 6 forms forms ((αα11-- αα66) thought to ) thought to confer specificity confer specificity of of BzBz actionaction

Bzbinding

site

27

BzRABzRA Efficacy: Nocturnal SleepEfficacy: Nocturnal Sleep

*p<0.005; ESZ vs. PBO for all comparisons*p<0.005; ESZ vs. PBO for all comparisons

******

00

1010

2020

3030

4040

5050

6060

7070

Month 1Month 1 Month 2Month 2 Month 3Month 3 Month 4Month 4 Month 5Month 5 Month 6Month 6

ESZ ObservedESZ ObservedPlacebo ObservedPlacebo ObservedESZ Completers (n=360)ESZ Completers (n=360)Placebo Completers (n=109)Placebo Completers (n=109)ESZ LOCF (n=593)ESZ LOCF (n=593)Placebo LOCF (n=195)Placebo LOCF (n=195)

Min

utes

Min

utes

Median Sleep Latency*:Median Sleep Latency*:Completed, Observed, and LOCFCompleted, Observed, and LOCF

Krystal et al., Krystal et al., Sleep Sleep 2003 26; 7932003 26; 793--799799**time required to fall asleeptime required to fall asleep 28

BzRABzRA Efficacy: Daytime Efficacy: Daytime ImprovementsImprovements

Recent studies with intermediate-acting BzRAs (e.g., eszopiclone and zolpidem CR) document that these drugs can improve daytime function (e.g., alertness) in patients with insomnia relative to placebo.

Krystal et al., 2003 Sleep Vol. 26., No. 7Krystal et al., 2008 Sleep Vol. 30, No.1

29

Insomnia Medications:Insomnia Medications:Potential for Adverse Effects Potential for Adverse Effects

Daytime drowsinessDaytime drowsinessCognitive and Cognitive and psychomotor psychomotor impairmentimpairmentDependenceDependenceRebound insomniaRebound insomnia

1. National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults June 13-15, 2005 Sleep Vol. 28

2. Krystal AD, Sleep Medicine Alert, National Sleep Foundation 2004 9:3. 30

Insomnia Medications:Insomnia Medications:Recent ConcernsRecent Concerns

Allergic reaction including angioedema

Complex sleep-related behaviors (CSB). Wake-like behavior, e.g., driving, performed without full cognitive awareness and for which the patient is subsequently amnestic. Incident and relationship to specific drugs or drug classes is unknown.

FDA Requests Label Change for All Sleep Disorder Drug Products, March 14, 2007http://www.fda.gov/bbs/topics/NEWS/2007/NEW01587.html (accessed 3.11.2008)

6

31

Melatonin and the Biological Melatonin and the Biological ClockClock

Adapted from Brzezinski A, Adapted from Brzezinski A, New England Journal MedicineNew England Journal Medicine 1997; 336:1861997; 336:186--195195 32

O

Ramelteon

Melatonin Agonists: Melatonin Agonists: RamelteonRamelteon

High selectivity and High selectivity and potency for potency for MT1/MT2MT1/MT2Negligible affinity Negligible affinity for other active for other active binding sites, binding sites, including including BzBz, DA, , DA, and opiate receptorsand opiate receptors

Kato K et al. Kato K et al. NeuropsychopharmacologyNeuropsychopharmacology 2005 48:3012005 48:301--310 310

H5C2CONHCH2CH2H

Ramelteon should not be used in patients with severe hepatic impairment or in combination with fluvoxamine.

33

Melatonin Agonists: EfficacyMelatonin Agonists: Efficacy

ZammitZammit G et al. G et al. Sleep Sleep 2005 28:Abstract Supplement A229. Abstract no. 06802005 28:Abstract Supplement A229. Abstract no. 0680

00

2020

4040

6060

8080

BaselineBaseline Week 1Week 1 Week 3Week 3 Week 5Week 5

LPS

(min

utes

)LP

S (m

inut

es)

Placebo n=131Placebo n=131RamelteonRamelteon 8 mg n=1388 mg n=138

**** **** ****

** P<0.05 (LS means for LOCF data)** P<0.05 (LS means for LOCF data)

34

Residual Pharmacologic Residual Pharmacologic EffectsEffects

All testing 8 hours postAll testing 8 hours post--dose. All comparisons N.S.dose. All comparisons N.S.

PlaceboPlacebo(N=103)(N=103)

Ram 4mgRam 4mg(N=103)(N=103)



Ram Ram 32mg32mg

(N=103)(N=103)DSSTDSST 47.447.4 47.347.3 46.546.5 47.747.7 47.547.5

MemMem. . immedimmed..

88 7.97.9 7.77.7 8.08.0 7.87.8

MemMem. . delayeddelayed

4.94.9 5.05.0 5.45.4 5.15.1 5.25.2

AlertnessAlertness 3.63.6 3.53.5 3.63.6 3.53.5 3.63.6

Ability Ability concenconcen

3.63.6 3.53.5 3.53.5 3.53.5 3.63.6

ErmanErman M et al. M et al. Sleep MedicineSleep Medicine 7:177:17--24, 200624, 2006

35

Abuse Liability of HypnoticsAbuse Liability of HypnoticsAbuse liability Abuse liability assessed as:assessed as:Likelihood of abuseLikelihood of abuseConsequences of Consequences of abuse (toxicity)abuse (toxicity)All All BzRAsBzRAs = class IV = class IV controlled controlled substancessubstancesMelRAsMelRAs = non= non--scheduledscheduled

Griffiths, R. R. and M. W. Johnson Griffiths, R. R. and M. W. Johnson Clinical PsychiatryClinical Psychiatry 2005 66 2005 66 SupplSuppl 9: 319: 31--414136

Part III: Treating Insomnia in Part III: Treating Insomnia in the Primary Care Settingthe Primary Care Setting

7

37

Defining SuccessDefining Success……

Insomnia patients suffer from a Insomnia patients suffer from a range of daytime deficits, health and range of daytime deficits, health and quality of life impairmentsquality of life impairments

Treating sleep symptoms has been Treating sleep symptoms has been shown to improve daytime function, shown to improve daytime function, perceived health, and quality of lifeperceived health, and quality of life

Krystal AD, Sleep Medicine Alert, National Sleep Foundation. 2004 9:3.38

Two Questions to Ask All Patients….

1.1. Are you having difficulty sleeping?Are you having difficulty sleeping?

2.2. If yes, does this problem affect you If yes, does this problem affect you during the day?during the day?

39

Follow-Up Questions

For patients answering For patients answering ““yesyes”” to 1 and 2:to 1 and 2:

•• How does it affect you during the How does it affect you during the day?day?

•• How long has this been a problem?How long has this been a problem?

•• Are you taking anything to help with Are you taking anything to help with this? If so, what?this? If so, what?

40

Why Can’t My Patient Sleep?

MedicationsAre all comorbidities accounted for?DepressionSubstance abusePrimary sleep disorder

41

Insomnia Management: Insomnia Management: Where Do I Start?Where Do I Start?

Considerations for patient care include:Considerations for patient care include:Duration of treatment Duration of treatment –– longlong--term or short?term or short?

PatientPatient’’s participation s participation –– is the patient likely is the patient likely to comply with behavioral interventions?to comply with behavioral interventions?

Potential for adverse effects Potential for adverse effects

Abuse liabilityAbuse liability

42

Consider Likely Duration of Consider Likely Duration of Treatment?Treatment?

Acute insomnia (< 4 weeks) can often be managed with a short course of hypnotics as the acute stress is resolved.

Treatment of chronic insomnia often involves multiple types of therapy (e.g., hypnotics, CBT).

8

43

Objective: Practice Parameters to Objective: Practice Parameters to Enhance the Diagnosis and Enhance the Diagnosis and

Treatment of InsomniaTreatment of Insomnia

1.1. Add sleep to ROS in order to identify patients Add sleep to ROS in order to identify patients presenting with other complaints presenting with other complaints

2.2. Facilitate patient education about sleep Facilitate patient education about sleep hygiene (e.g., handouts, Web pages)hygiene (e.g., handouts, Web pages)

3.3. Develop protocols to utilize full range of Develop protocols to utilize full range of available treatments as well as fallavailable treatments as well as fall--back back strategies when initial therapy failsstrategies when initial therapy fails

44

Additional Tools for the Evaluation of Insomnia

Sleep diaries – having patients keep a sleep diary for two weeks can help identify sleep symptoms as well as precipitating factors.

Polysomnography – for patients who snore and suffer from daytime sleepiness, polysomnography (overnight sleep study) can identify sleep disordered breathing.

45

Online Sleep Education Resources

Visit SleepFoundation.org for:Articles on sleep disorders such as insomnia and sleep apnea as well as a range of topics that may affect sleep (aging, depression, COPD, pain, fibromyalgia, pregnancy, etc.)

Sleep-themed games, quizzes, and other interactive educational tools

Downloadable sleep diaries

46

Broad Approaches to Broad Approaches to Insomnia Treatment:Insomnia Treatment:

Sleep hygiene education onlySleep hygiene education only

Combination of Combination of behavioral/pharmacologicalbehavioral/pharmacological

Pharmacotherapy onlyPharmacotherapy only

47

Objective: Components of an Effect Objective: Components of an Effect RiskRisk--Benefit Analysis Leading to an Benefit Analysis Leading to an

Insomnia Treatment PlanInsomnia Treatment Plan1.1. Complete a thorough evaluation, including Complete a thorough evaluation, including

history and physical examhistory and physical exam2.2. Assess degree of functional impairmentAssess degree of functional impairment3.3. Consider the risks/benefits of alternative Consider the risks/benefits of alternative

therapiestherapies4.4. Weigh the risks/benefits against those of Weigh the risks/benefits against those of

pharmacotherapy based on available datapharmacotherapy based on available data5.5. Assess abuse potential and adverse eventsAssess abuse potential and adverse events

48

My Patient has Insomnia. Now what?

If the problem is acute (< 4 weeks),

a. Identify precipitant and reverse where possible (e.g., new medication, incomplete post-op pain control, acute stress)

b. Education of sleep hygiene

c. Short course of medications if insomnia is likely to pose risks

9

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Case Study #1 Case Study #1 Ellen Ellen –– 80 Year80 Year--Old FemaleOld Female

Presenting complaint: worsening insomnia Presenting complaint: worsening insomnia and fatigue over the past two yearsand fatigue over the past two yearsSuffers from chronic arthritisSuffers from chronic arthritisPoor sleep 4Poor sleep 4--7 nights per week7 nights per weekFatigue is worse after poor night of sleepFatigue is worse after poor night of sleepDifficulty falling asleep most prominent, but Difficulty falling asleep most prominent, but also wakes too early (3also wakes too early (3--4 AM) 4 AM)

50

Case Study #1Case Study #1Considerations for TreatmentConsiderations for Treatment

Sleep symptomsSleep symptomsDaytime deficits Daytime deficits ComorbidityComorbidityAdverse effects with Adverse effects with BzRAsBzRAs (e.g., (e.g., dependence, dependence, psychomotor psychomotor impairment)impairment)

51

Case Study #1 Case Study #1 –– Question 1Question 1

How would you manage this patientHow would you manage this patient’’s s sleep complaint?sleep complaint?

1.1. BzRABzRA2.2. MelRAMelRA3.3. CBTCBT4.4. Observation/reassuranceObservation/reassurance

?

52

For Chronic or Recurrent Insomnia…

Develop a longer-term strategy:a. Identify precipitants/exacerbants and

reverse where possible (e.g., medications)b. Identify comorbidities and optimize current

treatment (e.g., DM, depression)c. Educate on sleep hygiened. If another sleep disorder is suspected or

patient fails to respond to therapy, consider polysomnography

53

Are Daytime Symptoms Present?

If there are no evident daytime consequences, educate on sleep hygiene and follow conservativelyIf daytime symptoms are present,

a. Consider behavioral therapy in all patients with chronic insomnia, but particularly in those who will not or should not take hypnotics

b. Consider pharmacologic therapy54

When Selecting Pharmacotherapy for Insomnia,

Consider that…

Approved agents are preferable to off-label agents

Newer BzRAs are preferable to older ones


10

55

Specific Considerations for Insomnia Pharmacotherapy…

Age of the patient

Sleep maintenance insomnia

Respiratory compromise

History of substance abuse

56

Case Study #2Case Study #2Carolina Carolina –– 29 Year29 Year--Old FemaleOld Female

Presents with sleep onset Presents with sleep onset insomnia since a breakinsomnia since a break--up up six months agosix months ago

Reports feeling Reports feeling ““very sadvery sad””

Uses alcohol as a sleep aidUses alcohol as a sleep aid

Medical history nonMedical history non--contributorycontributory

Family history of Family history of depressiondepression

57

Case Study #2 Case Study #2 -- Question 1Question 1

At this point in the evaluation, the At this point in the evaluation, the most likely diagnosis for this patient most likely diagnosis for this patient is:is:

1.1. Primary insomniaPrimary insomnia

2.2. Insomnia Insomnia comorbidcomorbid with alcoholismwith alcoholism

3.3. Insomnia Insomnia comorbidcomorbid with depressionwith depression

?

58

Case Study #2 Case Study #2 -- Question 2Question 2

How would you manage this patientHow would you manage this patient’’s s sleep complaint?sleep complaint?

1.1. Start antiStart anti--depressant medication and depressant medication and follow insomnia symptomsfollow insomnia symptoms

2.2. Start CBT for depression and insomniaStart CBT for depression and insomnia

3.3. Start antiStart anti--depressant and insomnia depressant and insomnia pharmacotherapypharmacotherapy

?

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Case Study #3Case Study #3Allison Allison –– 35 Year35 Year--Old FemaleOld Female

Eight months Eight months pregnantpregnant

Presents with Presents with insomnia due to insomnia due to anxiety about anxiety about pregnancy, labor, pregnancy, labor, birth, and birth, and motherhoodmotherhood

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Case Study #3 Case Study #3 –– Question 1Question 1

If pregnancyIf pregnancy--specific approaches & specific approaches & sleep hygiene are inadequate, how sleep hygiene are inadequate, how would you manage this patientwould you manage this patient’’s sleep s sleep complaints?complaints?

1.1. Reassure patient that this is a Reassure patient that this is a ““normal part normal part of pregnancyof pregnancy””

2.2. Add Add diphenhydraminediphenhydramine 2525--50 mg 50 mg qhsqhs

3.3. Add Add zolpidemzolpidem 10 mg 10 mg qhsqhs prnprn

4.4. Add Add temazepamtemazepam 7.57.5--30 mg 30 mg qhsqhs prnprn

?

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Pregnancy Safety Classification Pregnancy Safety Classification -- Commonly Commonly Used Medications for Sleep DisordersUsed Medications for Sleep Disorders

Pien GW and RJ Schwab, Sleep 2004 27(7): 1405-17

Note: ramelteon is Pregnancy Category C (Physicians Desk Reference)

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Case Study #4Case Study #4Liam Liam –– 50 Year50 Year--Old MaleOld Male

New patient reports history of chronic New patient reports history of chronic insomniainsomniaPrescribed zolpidem 10 mg Prescribed zolpidem 10 mg qhsqhs since since divorce almost three years ago divorce almost three years ago Recently discontinued because of Recently discontinued because of lapsed prescription lapsed prescription –– recurrence of recurrence of symptoms x 2 nightssymptoms x 2 nightsMedical history includes hypertension, Medical history includes hypertension, hypercholesterolemia, GERDhypercholesterolemia, GERD

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Case Study #4Case Study #4Question 1Question 1

Based on this patientBased on this patient’’s clinical s clinical presentation, how do you proceed?presentation, how do you proceed?

1.1. Resume Resume BzRABzRA2.2. Discontinue BzRA, initiate CBTDiscontinue BzRA, initiate CBT3.3. Discontinue BzRA, observe/reDiscontinue BzRA, observe/re--evaluateevaluate4.4. Evaluate for possible primary sleep Evaluate for possible primary sleep

disorderdisorder

?

64

Try, Try Again?Try, Try Again?

When should you When should you try alternative try alternative pharmacotherapy?pharmacotherapy?

65

Alternate Treatment ApproachesInadequate efficacy:

Review sleep hygiene, add CBT?Alternate drug class

Daytime sedation, psychomotor symptoms:

Reconsider CBTSwitch to MelRA

“Pharmacokinetic phailure:”Tailor duration of action to sleep complaint and morning function

66*Modified absorption prolongs duration of action*Modified absorption prolongs duration of actionPhysiciansPhysicians’’ Desk Reference. 1991, 1999 and 2007Desk Reference. 1991, 1999 and 2007

Approved BzRA HypnoticsApproved BzRA HypnoticsAgent Agent Dose (mg)Dose (mg) HalfHalf--life (h)life (h) ClassClass ApprovedApproved

LongLong--actingactingFlurazepam HCL Flurazepam HCL 15 or 3015 or 30 4747--100100 BZDPBZDP 19701970

Quazepam Quazepam 7.5 or 157.5 or 15 3939--7373 BZDPBZDP 19791979

IntermediateIntermediate--actingactingTemazepam Temazepam 7.5, 15 or 307.5, 15 or 30 3.53.5--18.418.4 BZDPBZDP 19821982EszopicloneEszopiclone 1, 2, or 31, 2, or 3 6.06.0 NONNON--BZDPBZDP 20042004Zolpidem MRZolpidem MR 6.25 or 12.56.25 or 12.5 1.41.4--4.5*4.5* NON=BZDPNON=BZDP 20062006

ShortShort--actingactingTriazolam Triazolam 0.125 or 0.250.125 or 0.25 1.51.5--5.55.5 BZDPBZDP 19791979

Zolpidem Zolpidem 5 or 105 or 10 1.41.4--4.54.5 NONNON--BZDPBZDP 19931993Zaleplon Zaleplon 5 or 105 or 10 1.01.0 NONNON--BZDPBZDP 19971997

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SummarySummaryInsomnia is a common complaint associated Insomnia is a common complaint associated with daytime impairmentwith daytime impairmentInsomnia is most often comorbid with other Insomnia is most often comorbid with other conditionsconditionsInsomnia has independent effects on comorbid conditions, daytime function, and QOL, and merits treatmentNew developments in therapy provide a wide range of empirically supported treatment options

insomnia pharmacotherapy - pri-med files/syllabus files_fall08... · session 7 session 7: insomnia...

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