Insomnia

difficulty falling asleep, difficulty maintaining sleep or experiencing Stimulus control procedures
nonrestorative sleep. 1. Establish regular times to wake up and to go to sleep (including
MC complaint in general medical practice weekends).
40% of pts with chronic insomnia have a psych diagnosis (depression, 2. Sleep only as much as necessary to feel rested.
anxiety, substance abuse) 3. Go to bed only when sleepy. Avoid long periods of wakefulness in bed.
10-20% self-medicate with OTC meds or alcohol Use the bed only for sleep or intimacy; do not read or watch television
3 types of Insomnia in bed.
Transient- lasting 2-3 nights (Ex. jetlag) 4. Avoid trying to force sleep; if you do not fall asleep within 20-30
Short-term- lasting < 3 months (Ex. situational) minutes, leave the bed and perform a relaxing activity (eg, read, listen
Chronic- lasting > 3 months to music) until drowsy. Repeat this as often as necessary.
Common causes of insomnia: 5. Avoid blue spectrum light from television, smart phones, tablets, and
Situational other mobile devices.
Work or financial stress, major life events, interpersonal 6. Avoid daytime naps.
conflicts, jet lag or shift work 7. Schedule worry time during the day. Do not take your troubles to bed.
Medical
Cardiac: angina, arrhythmias, HF Sleep hygiene recommendations
Respiratory: asthma, sleep apnea 1. Exercise routinely (three to four times weekly) but not close to bedtime
Chronic pain because this can increase wakefulness.
Endocrine: DM, hyperthyroidism 2. Create a comfortable sleep environment by avoiding temperature
GI: GERD, ulcers extremes, loud noises, and illuminated clocks in the bedroom.
Neurologic: delirium, Parkinsons, Seizures, RLS 3. Discontinue or reduce the use of alcohol, caffeine, and nicotine.
Pregnancy 4. Avoid drinking large quantities of liquids in the evening to prevent
Psychiatric nighttime trips to the restroom.
Mood disorders: depression, mania 5. Do something relaxing and enjoyable before bedtime.
Anxiety disorders: GAD, OCD OTC Options Not for long term use
Substance abuse: alcohol, sedative-hypnotic withdrawal Antihistamines
Drug-induced Insomnia Diphenhydramine (Tylenol PM, Sominex)
Anticonvulsants Doxylamine (Unisom)
Central adrenergic blockers Watch for anticholinergic side effects- esp. problematic in elderly
Stimulants Tolerance develops to sedative effects after 1 week
SSRIs, Bupropion Diphenhydramine- Pregnancy Category B; Lactation- may dry up milk
Steroids
Diuretics Herbal meds
How to determine management Melatonin
Determine if transient, short-term, or chronic Valerian
Assess onset, duration and frequency of sx Kava Kava
Assess effect on daytime functioning Little if any evidence of efficacy
Assess for underlying causes o Melatonin may be helpful in jet lag
Assess sleep hygiene o Hepatotoxicity reported with Kava Kava and Valerian root
Assess stress
Stepwise approach to select hypnotic
? Type of insomnia
Difficulty initiating sleep
Difficulty maintaining sleep/early morning awakening
? Duration
? Etiologies
Sleep apnea, psychiatric/medical issues
? Sleep habits
Substance abuse history
Select agents based on symptoms, kinetic and ADR profile

Clinical Practice Guideline General Treatment Approach

1. Short-intermediate acting BZD, Non-BZD RA or ramelteon
Ex. Zolpidem, eszoplicone, zaleplon, temazepam
2. Alternate short-intermediate acting BZD, Non-BZD RA or ramelteon
3. Sedating antidepressant
Ex. Amitriptyline, trazodone, doxepin, mirtazepine
4. Combined BzRA or ramelteon + sedating antidepressant
5. Other sedating agents- with appropriate comorbid conditions
Ex. Quetiapine, gabapentin

Non-pharm Tx
Cognitive behavioral therapy
May be more effective than drugs in > 55yo
Stimulus control, good sleep hygiene, cognitive therapy, relaxation
therapy
Benzodiazepines Zaleplon (Sonata)
MOA: GABA-A receptor agonists Onset: 30 min Duration: 2 hours
Controlled substance Useful to initiate sleep (quick onset); Can take in middle of night
Not 1st line but need 4 hr left in bed; Not for maintaining sleep unless redosed
Effective in time to fall asleep and total sleep time Least likely to cause next-day impairment or anterograde amnesia

Eszopiclone (Lunesta)
Onset: 45 min Duration = 5-8 hr
Useful to initiate sleep and maintain sleep long duration
No evidence of tolerance after 6 months of use
ADR: unpleasant/metallic taste (20-33% incidence)
Do not use in: Eszopiclone Dosing Change 2014
Pregnancy FDA recommended lower dose
Category X- cleft pallette, resp. depression Reason: 3mg dose can impair driving ability,
Breastfeeding- not recommended coordination, and memory for over 11 hours
Substance abuse Start with 1mg for all pts
Untreated sleep apnea Do not exceed 2mg for elderly and 3mg for young pts
Anterograde amnesia, an impairment of memory and recall of events
occurring after the dose is taken, can occur BZD and Non-BZD GABA-A agonists
Avoid use with alcohol and other CNS depressants FDA Labeling Changes
Caution with driving or operating heavy machinery Caution
ADRs: daytime sedation, psychomotor incoordination, decreased Anaphylaxis, facial angioedema
concentration and mental alertness, cognitive deficits, respiratory Complex sleep behaviors- engaging in these activities
depression while not fully awake and with no recollection afterwards
ADRs are dose-related- use lowest effective dose Sleep driving
Scheduled substance Sleep eating
Tolerance can develop, Can be habit forming Phone calls
Rebound insomnia can occur with abrupt DC Risk increased with concurrent alcohol use and
Can accumulate in the elderly lipid soluble doses above maximum recommended
Avoid BZDs with long t1/2- flurazepam and quazepam Ramelteon (Rozerem)
Inc. risk of falls and hip fracture MOA: Selective MT1 and MT2 receptor agonist
Onset: 30 min T1/2= 1-2.6 hours
Non-BZD GABA-A Agonists Effective for dec. time to fall asleep
Zolpidem (Ambien) Not effective for maintaining sleep
Zaleplon (Sonata) ADRs: HA, dizziness, somnolence
Eszopiclone (Lunesta) Not a controlled substance
MOA: selective GABA-A receptor agonist subtype 1 May be an option in substance abuse pts
Controlled substance Pregnancy Category C; Breastfeeding- unknown
High fat/heavy meal can delay absorption delays onset
CYP3A4 inhibitors can increase plasma levels Sedating Antidepressants
Hepatic impairment may require lower doses Alternatives for pt who cannot take BZD or if concommitant depression
ADRs: Improve sleep in depression with stimulating SSRI or bupropion
Headache Mostly see Trazodone used
Dizziness Doses used for insomnia are not effective for treating depression
GI: nausea, dyspepsia Amitriptyline 10-50mg Qhs; Doxepin (Silenor) 3-6mg Qhs
Anterograde amnesia (high dose zolpidem) Disadvantages
Withdrawal reactions uncommon but reported Anticholinergic side effects, adrenergic blockade
Pregnancy Category C; Breastfeeding: zolpidem compatible (orthostatic hypotension), cardiac conduction
problems, daytime sedation
Zolpidem Trazodone 25-150mg QHS
Formulations available: IR (Ambien), CR (Ambien CR), lingual spray Watch for orthostatic hypotension, priapism
(Zolpimist), SL (Edular, Intermezzo) Mirtazapine 7.5 30mg QHS
Useful to initiate and maintain sleep; some residual effects Watch for daytime sedation, weight gain
Intermezzo for middle of the night wakenings- Need 4h of sleep left
Suvorexant (Belsomra)
New class of sleep agent
MOA: orexin receptor antagonist
Orexins are involved with promoting wakefulness so
antagonising their effect would cause sedation
Schedule IV
Zolpidem Dosing Change 2013 Same precautions about combining with alcohol and other sedating
o FDA Recommends Lower Dose drugs and risk for impairment in driving and other activities the next day
o Reason: Morning blood levels in some pt (females) may be
high enough to impair activities requiring alertness driving
o Highest risk with ER forms and women eliminate the drug
more slowly than men
o Use 5mg vs. 10mg for IR; Use 6.25mg vs. 12.5mg for CR
o Intermezzo (no change) already at a lower dosage
(11/2011)