• NE
• DA
• 5-HT
• Histamine
• ACh
• Hypocretin/Orexin

• GABA
• Opioids (enkephalins, endorphins)
• 5-HT
• Adenosine
• Melatonin

• Relaxed wakefulness
• Initiates sleep

• Alpha wave light sleep
• Rest for brain/muscles

• Delta sleep, AKA deep sleep, AKA slow wave sleep
• Feeling of rejuventaion
• Immune system enhanced
• Growth hormone secreted
• Protein synthesis

• Rapid Eye Movement sleep
• Dreaming occurs
• Low muscle tone
• Learning and mood regulation
• 1st REM within 90 min of sleep onset

• α2δ ligands (gabapentin, pregabalin)
• GABA reuptake inhibitors (tiagabine)
• 5HT_2A/2C antagonist (trazadone)
• Partial GABA-b/GHB agonist (sodium oxybate)

• BZDs (increase stage 2, may prevent stage 4)
• Barbiturates (decreases latency, but suppresses REM)
• Serotonergic antidepressants (decrease SWS)
• Stimulants (decrease SWS)
• Stimulating antidepressants (bupropion)

Acute: < 30 days

Chronic: > 30 days

• Emotional or physical stress
• Environmental stressors (light, noise)

• Medical/psychiatric disorders
• Sleep scheduling (shift work)
• Medications
• Substance abuse

• Pain
• Heart failure
• Pulmonary disease
• Nocturia
• Hyperthyroidism
• Reflux, heartburn

• Anxiety
• Bipolar disorder
• Depression (10x greater with insomnia)
• PTSD
• Substance use

• Limit time to fall asleep to 20-30 min
• If pts are not asleep in set time period, they are instructed to leave the bedroom and engage in relaxing activity until they feel sleepy

• Pts attempt to stay awake for as long as possible, and fight the urge to sleep
• Results in decreased sleep latency when pt goes to bed
• Reduces sleep-related "performance anxiety"

• Develop regular sleep and wakefulness cycle
• Limit bedroom activities to sleep and intimacy
• Prohibit daytime napping
• Develop relaxing routine for 1 hr prior to sleep
• Exercise daily, but not within 2 hrs of bed
• Avoid late meals
• Avoid keeping clock near bed
• Avoid EtOH, caffeine, and nicotine

• BZDs
• Non-BZDs
• Ramelteon
• 1st Gen Antihistamines
• Antidepressants

Ex: Temazepam, Clonazepam, Lorazepam, Diazepam, Alprazolam

• May treat comorbid anxiety, if that is the cause of insomnia
• Should be tapered if used for greater than 30 days for risk of rebound insomnia, tolerance, addiction
• Higher abuse potential: euphoria
• Often worsen sleep apnea
• Decrease REM sleep and decrease SWS

Zolpidem, Zaleplon, Eszopiclone

• Similar efficacy to BZD with fewer side effects, and less rebound insomnia
• Less impact on sleep architecture than BZD
• Can cause impaired memory and motor skills deficits during daytime -- falls/hip fracture more likely in untreated insomnia

• M1 receptor and M2 receptor agonist
• M1 regulates sleepiness; M2 regulates day and night body phases
• Most useful for patients with trouble falling asleep --- melatonin increases at HS, antagonized by light
• Most studied for children

• Diphenhydramine, doxylamine, hydroxyzine
• Increases fall risk in elderly
• High anti-ACh side effects
• Limit to 7-10 days of use

Trazadone: 5-HT 2A/2C antagonist + H1 + α1

• used at subtherapeutic antidepressant doses (50-150 mg)
• Increases stage 3 and 4 sleep
• Can block slow wave sleep disruptions of SSRIs

Amitriptyline, Nortriptyline, Doxepin

• Anti-ACh effects
• Doxepin at 1-6 mg lacks M1 antagonist actions

Mirtazapine

• Inverse relationship between dose and sedation

Rapidly absorbed and short t1/2

• Zaleplon
• Ramelteon
• Triazolam

Long acting agents

• Zolpidem (including sustained release)
• Eszopiclone

• Drug therapy should not be chronic except in extraordinary situations (PRN use)
• Limit exposure to drugs to 4-6 wks in general

• Respiratory cessations during sleep with or without arousals to restore breathing
• Results in non-restorative sleep, decreased SWS, decreased REM, excessive daytime sleepiness
• Serious, potentially life-threatening condition -- associated with HTN, stroke, MI, arrhythmias, and all-cause mortality
• Diagnosed with overnight polysomnography

• Brain fails to initiate respirations
• BZD, EtOH, opiates, CNS depressants may prevent arousals that restore breathing

• Blockage of airway in the rear of throat
• Causes mini arousals -- fragmented and poor sleep
• As many as 20-30 arousals per hr

• M>F
• Increased weight (neck area)
• Increased age/decreased muscle tone
• Facial bone structure -- flat facial features
• Can affect any age group
• Mallampati Class ("crowded airway")

• CPAP gold standard or BiPAP
• Removal of tonsils/adenoids (pediatric)
• Uvulopalatopharyngoplasty
• Mandibular advancement (dental device to extend jaw)
• Weight loss
• Modafinil adjunct for excessive day-time sedation
• Fluoxetine/paroxetine may increase upper airway patency

• MOA unknown: DA, histamine, orexin
• Improves wakefulness in pts with excessive daytime sleepiness associated with narcolepsy and shift work sleep disorder -- adjunct for OSA

• CIV scheduled substance
• Caution in pts with cardiac abnormalities
• Monitor BP
• "Rash" -- Stevens-Johnson Syndrome/TEN, often within first 5 wks of therapy