Insomnia Pharmacotherapy A Practical Guide for Primary Care
Offices in Jacksonville, FL Fortis Spectrum is the educational partner for this session.
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.; sanofiaventis 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 estazolam flurazepam hydrochloride quazepam temazepam
Trade Prosom Dalmane Doral Restoril
Generic triazolam zolpidem tartrate eszopiclone zaleplon
Trade Halcion Ambien Lunesta Sonata
Session 7
Generic ramelteon tiagabine hydrochloride gabapentin pregabalin Investigational agomelatine indiplon epilvanserin M100907 ritanserin gaboxadol NGD96-3
Trade Rozerem Gabitril Neurontin Lyrica
Valdoxan
Off-Label trazodone nefazodone hydrochloride mirtazapine doxepin
Desyrel Serzone Remeron 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.
Session 7
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Course Objectives:
Insomnia Pharmacotherapy:
Define three practice interventions that will enhance the diagnosis and treatment of insomnia
Describe the components of an effective riskrisk-benefit analysis leading to an insomnia treatment plan
A Practical Guide for Primary Care
1
2
Insomnia Defined
Part I: Insomnia Overview
Complaint of inadequate or insufficient sleep despite adequate opportunity
Adversely affect waking function
3
4
Primary vs. Comorbid Insomnia
Prevalence of Specific Insomnia Complaints
No DSM-IV Diagnosis 24%
“Sleep disruption” disruption” in general population ~30%
Sustained insomnia with daytime functional impairment (= insomnia diagnosis) ~10%
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
Psychiatric Disorders 44%
Other Sleep Disorders 5%
Medical disorders 11% Primary Insomnia 16%
5
Ohayon MM. Sleep Medicine Review Review 2002; 6:976:97-111
1
6
Impact of Comorbid Disease on Insomnia Prevalence
Insomnia in Primary Care
Insomnia prevalence is increased in: Major psychiatric disorders, e.g., depression, anxiety, schizophrenia Neurological disorders, e.g., Parkinson’ Parkinson’s disease, dementia Medical disorders, e.g., COPD, diabetes
Primary sleep disorders, e.g., sleep apnea, restless legs syndrome
Roth T. and T. Roehrs, Clinical Cornerstone 2003 5(3): 5-15
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8
Insomnia and Comorbid Disease: A Circular Relationship Estimated Cumulative Probability of Onset
Time to Response Based on Clinical Global ImpressionImpression-Improvement Scale
Insomnia
Comorbid Disease 9
Treatment Eszopiclone 3 mg Placebo
ESZ + FLX PBO + FLX
P=.0002
0
5
10
15
20
25
30
35
Days to Onset of Response
40
45
50
Fava M et al; Biological Psychology 2006:59;1052-1060
Insomnia & Major Depressive Disorder
Fava M et al; Biological Psychology 2006:59;1052-1060
Eszopiclone in Patients with Insomnia Related to Major Depressive Disorder
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0
55 10
Consequences of Insomnia
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Increased risk of psychiatric disorders
Increased pain sensitivity
Decreased quality of life (QOL)
Motor vehicle and workplace accidents
Falls and hip fractures
Mortality 12
2
60
Recommended Insomnia Therapy
Part II: Insomnia Therapy
Chronic insomnia is a major public health problem affecting millions of individuals, along with their 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
13
Regular sleepsleep-wake cycle Regular exercise in the morning and/or afternoon Increase exposure to bright light during the day Minimize exposure to bright light at night Avoid heavy meals or drinking within 3 hours of bedtime Enhance sleep environment Avoid caffeine, alcohol and nicotine
Kupfer DJ, Reynolds CF. New England Journal of Medicine 1997; 336:341336:341-346
www.SleepFoundation.org
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Cognitive Behavioral Therapy for Insomnia
16
Efficacy of CBT Sleep Diary
80
Addresses the multiple factors that perpetuate insomnia
70
WASO (min)
14
Sleep Hygiene Patient Resource
Sleep Hygiene: An Essential Component of All Insomnia Treatment
Behavioral therapy - e.g., sleep hygiene, cognitive behavioral therapy (CBT) Approved pharmacological therapy
An Ideal CBT approach incorporates multiple modalities
Pre-Treatment
Polysomnography Post-Treatment
60 50 40 30 20
Success depends on trained therapist
10 0 CBT
PCT
CBT+ PCT
Plbo
CBT
PCT
CBT+ PCT
Plbo
WASO = Wake after sleep onset; CBT = cognitive behavior therapy; PCT = pharmacotherapy 17
18
Morin et al., JAMA 1999;281:991-999
3
Insomnia Pharmacotherapy in 2008
Nutraceutical Therapies
Nutraceuticals OTC agents OffOff-label prescriptive agents Approved prescriptive agents
“Internet therapies” therapies” No FDA oversight and fewer data Many GABAGABA-ergic An incomplete list: • • • • • •
Lavender German chamomile Mimosa blossoms Melatonin Valerian Root “Sleeping Buddha” 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
19
Most Common Rx for Insomnia 2002 prescribing data
Occurrences (Millions)
FDA WARNS CONSUMERS AGAINST TAKING DIETARY SUPPLEMENT "SLEEPING BUDDHA"
Source: http://www.fda.gov/bbs/topics/NEWS/NEW00625.html (accessed 2.28.2008) 21
Most commonly used agent in U.S. is trazodone
No positive efficacy data in nonnon-depressed patients
Can cause daytime sedation
Potentially significant adverse effects raising concerns about the riskrisk-benefit ratio
Over the Counter Sleep Agents (e.g., Diphenhydramine) Diphenhydramine) Advantages:
Prescription
Disadvantages 1,2:
Efficacy
not needed
not consistent supporting studies on efficacy in treating insomnia Potential for residual effects No wellwell-defined effective dose Limited
Rapid
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 Mendelson, WB, Clinical Psychiatry 2005 66(4): 469-76
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Walsh JK. Sleep 2004; 27:144127:1441-1442
Sedating Antidepressants
20
onset of tolerance
Kupfer DJ, Reynolds CF III. New England Journal of Medicine 1997 336:341336:341-346 Richardson et al., Clinical Psychopharmacology 2002 22:51122:511-515
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4
24
Diphenhydramine Tolerance
BzRA Hypnotics: Mechanism
Bz binding site
Sleep latency = time required to fall asleep Richardson et al., Clinical Psychopharmacology 2002 22:51122:511-515
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BzRA Efficacy: Daytime Improvements
BzRA Efficacy: Nocturnal Sleep 70
Median Sleep Latency*:
ESZ Observed Placebo Observed ESZ Completers (n=360) Placebo Completers (n=109) ESZ LOCF (n=593) Placebo LOCF (n=195)
Completed, Observed, and LOCF
60
Minutes
50
40 30 * 20
*
*
*
*
*
*p
