Download No Sleep Lost Over Treating Insomnia

Devon A. Sherwood, PharmD, BCPP
Assistant Professor
UNE College of Pharmacy
Clinical Psychopharmacology Specialist
Spring Harbor Hospital
Identify sleep stages and sleep cycles in a
typical nights rest to relate how changes in
these patterns affect sleep quality
Differentiate various causes, classifications
and presentations of insomnia
Explain the importance of sleep hygiene and
other non-pharmacologic therapies to help
counsel patients with insomnia
Compare therapeutic roles and
pharmacokinetic profiles of hypnotic
medications recommended in current
guidelines
Recognize inappropriate or contraindicated
medications
Advise patients' about potential adverse
effects of insomnia treatments
Which stage of sleep is when most
parasomnias occur (eg. child bedwetting), and
is known as restorative sleep characteristically
seen by predominant delta waves on a
polysomnograph?
A. REM
B. NREM Stage 1
C. NREM Stage 2
D. NREM Stage 3
E. NREM Stage 4
DR is a 42 yo male who is taking fluvoxamine for
OCD. His physician wants to prescribe a sleep aid
to help with antidepressant induced insomnia.
Which sleep aid is contraindicated in this patient?
A. Zaleplon
B. Ramelteon
C. Mirtazapine
D. Diphenhydramine
E. Suvorexant
DR is a 42 yo male who is taking fluvoxamine for
OCD. His physician wants to prescribe a sleep aid
to help with antidepressant induced insomnia.
Which agent would be the best choice in this
patient?
A.
B.
C.
D.
E.
Eszopiclone
Melatonin
Trazodone
Temazepam
Suvorexant
Nonrapid Eye Movement (NREM)
Stage I - Theta waves
Lightest sleep, easy to rouse
Stage II – More theta waves, sleep spindles
Deeper level of sleep
Stage III – Increase in delta waves (20%)
Deeper sleep
Stage IV – Delta waves (50%)
Deep sleep, difficult to rouse
Rapid Eye Movement (REM)
Frequent bursts of eye movement
activity that occur
Brain waves resemble Stage 1 (fast, low)
Harder to wake than Stage 1
Kaplan V, Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 9th edition 2009; ch 20: 2150-2161.
Which stage of sleep is when most
parasomnias occur (eg. child bedwetting), and
is known as restorative sleep characteristically
seen by predominant delta waves on a
polysomnograph?
A. REM
B. NREM Stage 1
C. NREM Stage 2
D. NREM Stage 3
E. NREM Stage 4
Develops within the first 2 years of life
Involves a 24.2 – 25 hour internal clock
Reset by external stimuli
Primary – Conditions inherent to the
mechanisms by which sleep is regulated
Parasomnia
Dyssomnia
Insomnia
Hypersomnia
Secondary – Sleep disturbances consequently
due to some other disorder
Kaplan V, Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 9th edition 2009; ch 20: 2150-2161.
Definition:
Difficulty falling asleep, maintaining sleep,
or not feeling rested despite a sufficient
opportunity to sleep
Epidemiology:
1/3 of US population reports insomnia
17% reported the symptoms to be serious
SH is a 25yo BF who comes into you community
pharmacy complaining she can’t sleep. She tells
you she started having problems during this past
semester in pharmacy school after exams. Upon
questioning, the patient tells you she drinks “a lot”
of caffeine and never goes to bed the same time
every night since she stared school this past fall.
She is requesting for something to help her sleep
now that the problem is persisting into the next
semester. Currently, her only medication is
Fluoxetine (Prozac®) 60mg QHS.
What other questions should you ask the
patient before making a recommendation?
What classification for insomnia is SH likely
experiencing?
What strategies could she implement to help
her improve this condition?
Patient Case
What medications would you recommend for
SH?
Are there any drug interactions to be concerned
with?
Situational –
stress, conflicts, jet lag
Medical –
cardiovascular, pain, respiratory, endocrine
disorders, GI, neurologic, pregnancy
Psychiatric –
mood disorders, anxiety, substance abuse
Pharmacologically Induced –
anticonvulsants, central adrenergic blockers,
diuretics, SSRI’s, steroids, stimulants
Dipiro JT, Pharmacotherapy
Inadequate Sleep Hygiene
Psychophysiological Insomnia
Sleep State Misperception
Idiopathic Insomnia
Kaplan V, Kaplan & Sadock’s Comprehensive Textbook of
Psychiatry, 9th edition 2009; ch 20: 2150-2161.
Short-Term (Acute) vs. Long Term (Chronic)
Acute Insomnia:
Overall, non-benzodiazepines (Z-drugs) or in specific
patients with comorbidities sedative antidepressants
are preferred
Eszopiclone, zolpidem, and suvorexant may improve
short-term global and sleep outcomes for adults with
insomnia disorder
Caution even in short-term treatment, as pharmacotherapies
for insomnia may cause cognitive and behavioral changes
and have been associated with infrequent but serious harms
Wilt T, et al. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the
American College of Physicians. Annals of Internal Medicine 2016: 165(2)
Chronic Insomnia:
CBT is 1st line therapy
If CBT unsuccessful, weigh risk vs. benefit of
medications as evidence of benefit is weak
Comparative effectiveness and long- term efficacy of
pharmacotherapies are still not established
Qaseem A, et al. Management of Chronic Insomnia Disorder in Adults: A clinical Practice Guideline
from the American College of Physicians. Annals of Internal Medicine 2016: 165(2).
Wilt T, et al. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice
Guideline by the American College of Physicians. Annals of Internal Medicine 2016: 165(2)
Cognitive behavioral therapy
Stimulus control
Sleep hygiene
Relaxation therapy
Light therapy
Sleep deprivation
Up to 80% of people with insomnia
treated nonpharmacologically have a
positive response.
Maintain regular hours of bedtime and
arising
Do not eat heavy meals before bedtime
Avoid napping during the daytime
Exercise daily
Avoid “clock watching”
Minimize cigarette smoking and caffeine
before bedtime
Release worrisome thoughts before
bedtime
Make the bedroom comfortable
Avoid alcohol as a sleep aid
Valerian Root
Melatonin
Kava Kava (not recommended)
Diphenhydramine and Doxylamine
[Rx hydroxyzine pamoate (Vistaril®)]
Branded as several products
Diphenhydramine: Benadryl, Diphenhist, Unisom
Gelcaps, Nytol, Simply Sleep, Sleepinal, Sominex,
Twilite, Tylenol PM
Doxylamine: Good Sense Sleep Aid, Unisom
Sleep Tabs
MOA – competes with histamine for H1receptor sites; also Ach effects
Problems with antihistamines:
Tolerance
Hangover
Barbiturates
Chloral Hydrate
Antidepressants
Trazodone
Mirtazapine
Amitryptiline
Doxepin
Preferred for treating:
Antidepressant Induced Insomnia
Insomnia due to depression or anxiety symptoms
Generally low doses work best and have
minimal to no side effects
Trazodone most widely used
Monitor Mirtazapine for ADR
Weight gain, HTN, Diabetes Mellitus
Silenor® ultra-low-dose brand (doxepin 3mg or 6mg)
vs. generic doxepin 10mg
Zolipidem (Ambien®, Intermezzo®, others)
Zaleplon (Sonata®)
Eszopiclone (Lunesta®)
All have same MOA: Selectively act on BZD1
receptor
FDA Black Box Warning: Abnormal thinking,
behavioral changes and complex behaviors:
May include “sleep-driving”
Any new onset behavioral changes need evaluation
As effective as BZD hypnotics with little
effect on sleep stage
Not associated with tolerance or rebound
after 35 days of use
Due to MOA which selectively acts on BZD1
receptor:
Minimal anxiolytic effects
No muscle relaxant or
anticholenergic effects
Ambien®, Ambien CR®, Intermezzo®, Edular®, Zolpimist® Packaage Inserts
Dose for Men:
Zolpidem IR or Edular® SL : 5 to 10 mg (max 10 mg)
Ambien CR: 6.25 to 12.5mg (max 12.5 mg)
Intermezzo® SL: 3.5 mg (max 3.5 mg)
Dose for Women:
Zolpidem IR or Edular® SL : 5 mg (may increase to max
10mg)
Ambien CR: 6.25 mg (may increase to max 12.5mg)
Intermezzo® SL: 1.75 mg (may increase to max 3.5mg)
Elderly & hepatically impaired = lowest doses only
PK:
T½ = 2.5h
Duration of action (sleep effects) = 6 - 8 hours
No significant rebound insomnia,
withdrawal symptoms, daytime
anxiety or daytime sedation
No psychomotor impairment,
or memory impairment
Most common SE are
dizziness, HA, and
somnolence
Sonata® package insert
Dose:
10 mg nonelderly adults
5 mg elderly
PK:
Rapid onset, short duration of effects
T½ = 1 hour
Duration = 3 hours
FDA approved for long term use
No evidence of tolerance throughout 6
months of nightly use
Most common side effects are unpleasant
taste, headache and somnolence
Dosing:
2 mg qhs in nonelderly patients, then
increase to 3 mg if necessary
1 mg qhs in elderly, severely hepatic
impairment, or concurrently administered
potent CYP 3A4 inhibitors
PK:
T½ = 6 h
Duration = 7 - 8 hours
NO evidence of abuse or dependence
OR impaired daytime wakefulness
MOA:
Melatonin receptor agonist with high
affinity for MT1 and MT2 and selectivity
over the MT3 receptor
No affinity for GABA receptors
Side effects include fatigue, dizziness,
drowsiness
Dose:
8 mg qhs
PK:
T½ = 1-2.6 h
2-5 hours (active metabolite)
Metabolized by CYP 1A2 – watch for DDI’s!
Quick onset and duration of action
Median peak concentration occurs at 0.75 h
DR is a 42 yo male who is taking fluvoxamine for
OCD. His physician wants to prescribe a sleep aid
to help with antidepressant induced insomnia.
Which sleep aid is contraindicated in this
patient?
A. Zaleplon
B. Ramelteon
C. Mirtazapine
D. Diphenhydramine
E. Suvorexant
Five BZD are FDA approved for insomnia:
Estazolam, Flurazepam, Quazepam,
Temazepam, Triazolam
MOA of BZD:
Nonselectively binds to BZD receptors
Increase stage 2 sleep, decrease stage 1 and
4 sleep – Do not decrease REM sleep
Increase total sleep time
Decrease latency to sleep onset and number
of awakenings
Benzodiazepines Used for Insomnia
Micromedex® 2016
Orexin receptor antagonist
Approved for insomnia with sleep onset and/or sleep
maintenance difficulties
The orexin neuropeptide signaling system is a central
promoter of wakefulness.
Blocking the binding of wake-promoting neuropeptides
orexin A and orexin B to receptors OX1R and OX2R is
thought to suppress wake drive.
Use the lowest dose effective
Dose = 10 mg po within 30 minutes of bedtime
No more than once per night
At least 7 hours remaining before planned awakening
If the 10 mg dose is well- tolerated but not effective,
increase dose not to exceed 20 mg once/night
Time to effect may be delayed if taken with or soon
after a meal
CYP 3A4 DRUG INTERACTION!
Dose = 5mg if moderate interaction, 10mg maximum
AVOID use with strong CYP 3A4 inhibitors
DR is a 42 yo male who is taking fluvoxamine for
OCD. His physician wants to prescribe a sleep
aid to help with antidepressant induced
insomnia.
Which of the following medications would be the
best choice in this patient?
A.
B.
C.
D.
E.
Eszopiclone
Melatonin
Trazodone
Temazepam
Suvorexant
Diagnosis
Insomnia has a high prevalence – Usually an
underlying problem, not a primary disorder
CBT & Sleep Hygiene first!
Nonpharmacologic treatment first, then
pharmacologic therapies
Appropriate Drug Selection
Pharmacokinetics
Drug-drug interactions
Drug-disease interactions
SH is a 25yo BF who comes into you community
pharmacy complaining she can’t sleep. She tells
you she started having problems during this
past semester in pharmacy school after exams.
Upon questioning, the patient tells you she
drinks “a lot” of caffeine, never goes to bed the
same time every night since she stared school
this past fall.
She is requesting for something to help her
sleep now that the problem is persisting into
the next semester. Currently, her only
medication is Fluoxetine (Prozac®) 60mg QHS.
What other questions should you ask the
patient before making a recommendation?
What classification for insomnia is SH likely
experiencing?
What strategies could she implement to help
her improve this condition?
Patient Case
What medications would you recommend for
SH?
Are there any drug interactions to be concerned
with?
www.vectorstock.com
CE Test Questions:
Which of the following medication can effect
the sleep cycle (ie. increase or decrease any
stage of sleep)?
SELECT ALL THAT APPLY:
A. estazolam
B. triazolam
C. temazepam
D. eszopiclone
E. zaleplon
CE Test Questions:
Which of the following is NOT
associated with next day hangover?
A.
B.
C.
D.
E.
diphenhydramine (Unisom)
quazepam (Doral)
suvorexant (Belsomra)
ramelteon (Rozerem)
zaleplon (Sonata)
CE Test Questions:
KZ is a 45yo BF who travels often. The physician
would like help her sleep flying across the country.
She has no comorbidities or current medications.
The physician specifically asks if you know of a
medication that only lasts a few hours, so she will
not have any residual effects. Which of the following
would be BEST CHOICE to give KZ at this time?
A.
B.
C.
D.
E.
eszopiclone
zaleplon
doxylamine
temazepam
valerian root
CE Test Questions:
TE is a 48yo WM complaining of trouble falling
asleep. He reports this started last week when he
began taking Wellbutrin XL® (bupropion) 150mg po
QAM for depression. He has no comorbidities or
other medications. Considering TE’s trouble falling
asleep is likely due to his new antidepressant
medication, which of the following medications
used for insomnia would be best to recommend?
A.
B.
C.
D.
E.
Trazodone
Imipramine
Zolpidem
Temazepam
Ramelteon
Devon A. Sherwood, PharmD, BCPP
[email protected]