Insomnia, Sleeping Pills and

Adults
Robert Daniel Vorona MD
August 9, 2019
Conflicts of Interest
 Who Needs Sleep?

My hands are locked up tight in fists

My mind is racing filled with lists
Of things to do and things I've done
Another sleepless night's begun

Barenaked Ladies Who Needs Sleep 1998

 Goals of Todays Talk

• Define insomnia (ICSD 3)-focus on chronic insomnia

• Epidemiology of insomnia and sleeping pill use
• Consequences of insomnia
• Differential Diagnosis of Insomnia
• Sleeping Pills for Adults
• Side effects of sleeping pills
• An approach to insomnia
No Sleeping Pill vs. Sleeping Pill
 Question 1

What duration must insomnia last to be defined as chronic?

• 1 months
• 3 months
• 6 months
• 12 months
 Definition of Chronic Insomnia

“The essential feature of chronic insomnia disorder is a frequent

and persistent difficulty initiating or maintaining sleep that results
in general sleep dissatisfaction.”
• At least three months
• 3 + days a week
• Must have an opportunity to sleep
• Impact on daytime function

International Classification of Sleep

Disorders Third Edition 2014
 Question 2

What percentage of the population has an insomnia diagnosis?

• 2%
• 5%
• 10%
• 33%
 Epidemiology of Insomnia

• Prevalence depends on definition

• Insomnia symptoms 20-45%
• Insomnia diagnosis 4-22%
• Chronic insomnia roughly 10% of population
• Insomnia is the most common sleep disorder

Principles and Practice of Sleep

Medicine 6th Edition
Kryger, Roth, Dement 2017
 Question 3

What percentage of acute insomnia patients develop chronic

insomnia?
• 5%
• 15%
• 20%
• 50%
 Acute to Chronic Insomnia

• Per Ellis et al. in data from the USA and UK

• Annual incidence of acute insomnia 30%
• 78% remission rate
• 21% chronic insomnia

Ellis J et al. J Psychiatr Res

2012;46:1278-85.
 Insomnia Outpatient Numbers

• National Ambulatory Medical Care Survey information from

1996-2001 (weighted national data on outpatient visits)
• 4.8 billion visits
• 94.6 visits estimated for sleep complaints

Balkrishnan R et al Sleep
2005;28:715-719.
 Office Visits

Ford E et al. Sleep 2014;37: 1283-1293

 Who gets Insomnia?

• Women > men (1.4X symptoms and 2X insomnia dx)

• Elderly > symptoms with age and 50% by 65 years
• Women > men discrepancy > with age
• > in separated and divorced
• Medical problems
• > mood disorders (depression and anxiety)-bidirectional

Ohayan MM Sleep Med Rev 2002;6:97-11

Morphy et al. Sleep 2007; 30:274-280.
Ellis J et al. J Psychiatr Res 2012;46:1278-
85.
 Deployed Military and Sleep Problems

Peterson A et al. Mil Med 2008; 173:230-

235.
 Breast Cancer and Insomnia

• Insomnia is common in cancer 252,710 new cases

invasive breast cancer in
• 2019 study on insomnia and breast cancer USA 2017
ACS Facts and Figures
• N=173 with new breast cancer diagnosis 2017-2018

• Followed for 1 year

• Pre DX-25% with “sleep disturbance” and 8% with “insomnia
syndrome”
• With DX up to 46% and 18% respectively
• Over time persisted at 50% and 21% respectively

Fleming L et al. Sleep 2019; 42: 1-10.

 Cost of Insomnia

• $2000 more a year health care in insomnia pts (Kleinman

2009)
• Direct costs 2-16 billion/year
• Indirect costs 75-100 billion/year (e.g. reduced productivity,
work associated mishaps)

1. Kleinman NL et al. J Clin Psychiatry

2009;70:1098-104.
2. Sateia M et al. JCSM 2017;13:307-349
 Sleeping Pill use in the USA

4% US adults >20 years used sleeping pills in last month

Chong Y et al. NCHS Data Brief

2013;127:1-8
 Sleeping Pills-Age and Ethnicity

Chong Y et al. NCHS Data Brief

2013;127:1-8
 Increasing sleeping pills with Education

Chong Y et al. NCHS Data Brief

2013;127:1-8
 Question 4

Which sleeping pill class did NOT seen an increase in

prescriptions from 1999 to 2010?
• Benzodiazepines
• Non-Benzodiazepines
• Z drugs (zaleplon, zolpidem, eszopiclone)
 # Visits to Office with Sleep Pill Prescriptions

Ford E et al. Sleep 2014;37: 1283-1293.

 Question 5

What is the estimated cost for 100 pills of Ramelteon?

• 100 dollars
• 200 dollars
• 500 dollars
• 1400 dollars
 Sleeping Pills Costs

Consider
the $

Janto K et al. J Clin Sleep Med

2018;14:1399-1408.
 Consequences of Insomnia

• Mood disorders (Szklo-Coxe et al. Am J Epidemiol 2010;171:709-720 and Sivertsen et al. J Sleep Res 2014;
23:124-32)

• PTSD and Suicidal Ideation Post Deployment (Wang et al. Sleep 2019; 42:1-9)
• Falls (Cauley et al. JBMR 2019;34:464-474)
• Hypertension (Jarrin et al. Sleep Med Rev 2018;41:3-38)
• Myocardial Infarction (Sivertsen et al. J Sleep Res 2014; 23:124-32)
• Motor Vehicle Crashes (Leger D et al. Sleep 2006;29:171-8)
• Absenteeism (Especially blue collar) (Leger D et al. Sleep 2006; 29:171-8)
 Differential Diagnosis-What to ask?

• Sleep environment
• Inadequate sleep hygiene
• Mood disorders
• Physical complaints
• Sleep Disorders (OSAS and RLS)
• Medications
• Circadian Rhythm Disorders
• Psychophysiological Insomnia
 Question 6

The first line treatment for chronic insomnia is?

• Zolpidem
• Eszopiclone
• Low dose doxepin
• Suvorexant
• None of the above
 Sleeping Pills-FDA Approved

• Antihistamines
• Benzodiazepines
• Non-Benzodiazepine Z drugs
• Melatonin agonists
• Dual orexin receptor antagonists
• Tricyclic anti-depressants
 FDA Approved Sleeping Pills Chart

Janto K et al. J Clin Sleep Med 2018;

14: 1399-1408
 American Academy of Sleep Medicine
Recommendations

Sateia M et al. J Clin Sleep Med

2017;13:307-349.
 Most Common Sleeping Pills Prescribed in
Military Health System
• Active duty more likely than non to be prescribed (2-3% higher)

Jean R et al. J Clin Sleep Med

2019;15:873-879.
 How well do BZRA’s work?
#193 (72% female)
55 years
77% responded (ISI >6)
48% remitted (ISI <11)
Comorbid disorders and
Psychiatric disorders >
doubled persistent insomnia
rate

Pillai V et al. Sleep 2017;40:1-9.

 Melatonin after Traumatic Brain Injury (TBI)

• After TBI, insomnia and hypersomnia common

• May be alterations (reduced and delayed) in melatonin profiles
after TBI
• Trial of melatonin 2mg for 4 weeks for post TBI sleep difficulties
• Better sleep quality on PSQI
• Higher sleep efficiency (per actigraphy)
• No improvement in time to sleep or daytime sleepiness

Grima N et al. BMC Medicine

2018;16:8 DOI 10.1186/s12916;017-
0995-1
 Z drugs and Abuse and Dependence

• Benzodiazepines well known for problems with

abuse/dependence
• Initial thought Z drugs much safer may be incorrect
• European study of (zaleplon, zolpidem, zopiclone)
• N=33,240 “…misuse- ,abuse-, dependence-, and withdrawal-
related adverse drug reactions, corresponding to some 6246
unique patients….were identified”

Schifano F et al. Int J

Neuropsychopharmacol 2019; 22:270-
277.
 BZRA’s, TBI and Fractures
• Tom et al (2016) looked at Z drugs (zolpidem, eszopiclone,
zaleplon)
• Patients >65 years
• 5% Medicare beneficiaries with TBI or Hip Fracture

Tom S et al. Sleep 2016;39:1009-

1014.
 Sleeping Pills and Crashes

• Swedish study
• Ages 50-80 # 26,586
• Assessed crashes 1/2006-12/2009
• Compared controls to “…new, occasional, and frequent use of
zolpidem only, zopiclone only, and combined zolpidem and
zopiclone.”
• Increased risk crashes both in new and frequent users!

Nevriana A et al. CNS

Drugs 2017;31:711-22.
 Zolpidem and crashes in the Aged

• US (Alabama) study of 70+ year olds # 2000

• Zolpidem usage assessed by pill bottle review
• Alabama Dept of Public Safety records
• Women more likely to have crashes
• >80 years more likely to have crashes

Booth J et al. SleepMed 2016;

20:98-102.
 Zolpidem and Parasomnias

• Sleep walking
• Sleep driving
• Sleep eating
• Sleep sex

Poceta J Clin Sleep Med

2011;7:632-638
 Parasomnias/Serious Adverse Events
Not just Zolpidem
• Eszopiclone and suicide attempt
Pennington J. Innov Clin Neurosci
2016;13:44-48.
• Suvorexant with suicidal ideation in CAPD
patient with mood disorder
Petrous J and Furmaga K BMJ Case Rep 2017.
doi:10.1136/bcr-2017-222037.
 “Short acting” sleeping pills and cognitive
impairment
• Thought is short acting pills should not impair daytime function
• Small study from Japan N=13 males age 23 years
• Administered either zolpidem 5mg or triazolam 0.25mg
• Half lives 2.8 and 1.5-5.5 hours
• Assessed cognitive function 12 hours later
• Sleepiness resolved
• Attention and Working memory impaired as well as “alertness”,
“vigor”, and “sadness”
• What does this mean for the typical sleeping pill patient?
 Sleeping Pills and Dementia

• Billioti de Gage et al. (2014)

• # 1796 Quebecois dx with Alzheimer disease (followed > 6
years) vs. 7184 controls
• 66 years +
• Looked at association benzodiazepines and subsequent
Alzheimer disease
• BZ begun > 5 years before DX of Alzheimer
• > risk (1.52 OR) for BZ use
• Dose response for increased amount of use
• More likely with longer acting agents
 Sleeping Pills and Infections

• Sleeping pills may be associated with increased risk of

infection
• Joya et al. study FDA records for 3 Z drugs and Ramelteon
• N=8828 with sleeping pills
• N=4383 with placebo
• Infection rate 1.44 greater (p<.00001)
• Most per authors mild
• ? GERD ? Immune alterations
 Sleeping Pills and Mortality

Choi J-W et al. J Clin Sleep

Med 2018;14:1669-1677.
 Question 7

Approximately what percentage of older patients who stopped

sleeping pills stay off at 3 years?
• 75%
• 50%
• 30%
• 10%
 Persistent withdrawal from Sleeping Pills

• Finnish study of 93 subjects >55 years

• Stopped Temazepam, Zopiclone, Zolpidem
• Followed for 3 years to assess successful abstinence from
sleeping pills
• 28% off still at 3 years
• 33% “regular users” at 3 years

Puustinen J et al. BMC Geriatrics

2018 18:142
https://doi.org/10.1186/s12877-
018-0829-9
 My Suggestions

• Ask what they mean by they cannot sleep (even if this requires
a second appointment)
• Treat the specific problem(s)
• If CBT-I available, please consider (first line therapy)
• Smallest dose needed
• Consider factors like age, hepatic, renal impairment
• Consider following AASM guidelines for use of specific drugs
for sleep onset and sleep maintenance insomnia
• Avoid using anti-depressant (except for low dose Doxepin) for
insomnia alone
• Re-evaluate for effectiveness and side effects
Thank You and Questions