- Anxiety

- Bipolar

- Cancer

- CVD

- Depression

- GERD

- Pain

- Pregnancy

- Alcoholism

- Stimulants

- Anticonvulsants

- Antidepressants

- Antihypertensives

- Steroids

- Body's biological clock

- Controlled by Superchiasmatic nucleus

- Can function without light cues

- Signals body to enter sleep

- Sleep cycle itself is altered throughout the life cycle

- Serotonin

- GABA

- Adenosine

- Cholecystekinin

- Enkephalin

- Endorphin

- NE

- DA

- Ach

- Histamine

- Substance P

- Glutamate

- Corticotropin releasing factor

- Primarily controlled by serotonin

- Average adult 4-5 cycles/8 hours

NREM Stages 1-4:

1:  Relaxed wakefulness, falling asleep

2:  Asleep, muscle activity slows, 50% of sleep occurs here

3 and 4:  Deep sleep, most of first 1/3 of the night, restfull sleep that leaves individual rejuvenated, Difficult to arise from the stages, may appear disoriented, when body "rebuilds" itself.   

- Body and brain stem in deep sleep

- Higher cortical brain functions are active

- Dreaming --> most of last 1/3 of night

- Uses cholinergic cells

- Abnormality in amount, quality, or timing of sleep

- Primary insomnia

- Takes > 1/2 hours to fall asleep (waking up during night or early morning

- <6 hours total sleep

- Periodic limb movement during sleep

- RLS

- Sleep apnea

- Narcolepsy

- Abnormal behavioral or physiologic events associated with sleep

Includes: Sleep walking, Sleep terrors, Primary snoring, Medical/substance induced

Transient - lasting a few days

Short term - Lasting < 3 weeks

Chronic/Persistent - Lasting > 3 weeks

- Enhance associated daytime function

- Improvement of energy

- Attention or memory difficulties

- Cognitive dysfunction

- Fatigue or somatic symptoms

Improvement in insomnia markers:  SOL (Sleep onset latency), WASO (wake time after sleep onset), number of wakenings

- Formation of a positive/clear association between the bed and sleeping

- Achieve balance of efficacy and actual side effects

- Short term CBT

- Maintain consistent schedule

- Exercise regularly

- Avoid napping

- Bedroom atmosphere

- Avoid alcohol, nicotine, caffeine, or large amounts of fluid

- Establish a bedtime ritual

- Remelton

- Benzo's/Non-Benzo receptor antagonists (BzRa) hypnotics

- Antihistamines/anticholinergics

- Antidepressants

- Chloral hydrate

- Initiate sleep onset within 20 minutes

- Allow patient to sleep throughout the night

- No daytime impairment

- No tolerance or dependence

- Example: Remelteon (Rozerem)

- Works on melatonin rececptors in Superchiasmatic nucleus

- Well tolerated, trigger for circadian rhthym

- Best for difficulty falling asleep, improves sleep latency

- Preferred in substance abuse or patients wanting to avoid CII

- 8mg at bedtime, no titration 

- Benzo Omega 1 receptor agonist

- Greater efficacy than OTC or antidepressants

- Safer in acute overdose and better tolerated than barbituates

- Zaleplon/Zolpidem, shorter T 1/2 so better for sleep onset latency

- Eszoplicone better for sleep maintenance (WASO)

- All benzos are effective, 5 agents for insomnia

- Bind to Gaba receptors

- Decrease latency, REM, stage 3 and 4 sleep, may result in REM rebound with discontinuation

- Increases total sleep time and stage 2 sleep

- Used for all types of insomnia

- Should be used sparingly

- Triazolam: 2 week to develop tolerance, withdrawal and rebound insomnia, CNS effects

- Tolerance could develop quickly

- Dose: 0.5-2g at bedtime

- Problematic AE: GI upset or disorientation

- Dependence and Toxic in overdose

- Pediatric use 10-50 mg/kg at bedtime

- Trazodone

- Mirtazapine

- Doxepin

- Amitriptyline

- Trimipramine

- BzRA's and melatonin receptor agonists are FDA approved and preferred

- Each generally safe and effective for short term

- OTC antihistamines do not improve sleep architecture and have advers effects in elderly

- For comorbid depression try sedating using low-dose antidepressant

- Positive pressure devices

- Weight reduction

- Surgery:  Uvulopalatopharyngoplasty

- Positional therapy

- Avoid all CNS depressants and medications that promote weight gain

- No currently approved therapy for OSA

- Excessive daytime sleepiness

- "Sleep attacks" up to 30 minutes

- Cataplexy:  Sudden bilateral loss of muscle tone in 75% of patients

- 70% also experience hallucinations that start in attack, but go into wakefullness

- Counseling of pt. and family

- Good sleep hygiene, 1-2 scheduled naps per day

- Treatment focused on EDS (excessive daytime sleepiness) and cataplexy

- Side effects of stimulants include insomnia, hypertension, palpitations, irritability

- Tolerance can occur in long-term use (leading to dose increase)

- Referred to as RLS

- Characterized by paresthesis felt deep in calf muscle

- Males = females in prevalence

- More common in the elderly

- Dopamine agonists, preferred over Levodopa ( Ropinirole, Pramipexole)

- Sedative Hypnotics: Clonazepam (widely studied), if want to decrease daytime sleepiness use: Zolpidem, Zaleplon, Triazolam

- Opiates work well for painful RLS: Methadone 5-20mg, Codeine 30-120mg, Oxycodone 2.5mg