CNS Sleep pt 1

Categories of sleep disorders

- Insomnia Disorders

- Narcolepsy

-Breathing-Related Sleep Disorders

- Circadian Rhythm Disorders

- Restless Legs Syndrome

Sleep Cycles

- Non REM Sleep (75%)

- REM Sleep (25%)

Non REM sleep

- 4 stages

- 1&2: wakefulness / light sleep

- 3: delta sleep

- 3&4: metabolic activity and brain waves slow (deep sleep, no eye movement)

REM sleep

- Rapid eye movement

- Muscle paralysis

- Dreaming

- Brain is MORE active

Arousal Systems (wakefulness & sleep)

- Main stages / transitions of wakefulness / sleep

Insomnia

- Trouble initiating or maintaining sleep associated with daytime consequences

- Transient: lasts days

- Short term: less than 3m

- Long / chronic: >3m & 3x / week

Causes of Insomnia

- Situational: work, financial stress, major life events, conflicts, jet lag

- Medical: CV, respiratory, chronic pain, GI, pregnancy

- Psychiatric: mood disorders, anxiety, substance abuse

- Pharmacologically induced: anticonvulsants, central adrenergic blockers, diuretics, SSRIs

Treatment for Insomnia

- Start with non-pharm (OTC, CBT, Sleep hygiene)

- If persists >14 days discuss pharm options

- Choice depends on type of insomnia

Falling asleep insomnia

- Eszopiclone

- Zolpidem

- Ramelteon

- Zaleplon

Staying Asleep insomnia

- eszopiclone

- zolpidem

- doxepin

- suvorexant

Both falling asleep and staying asleep insomnia

- Eszopiclone and Zolpidem (remember EZ)

Non pharm treatment

- Stimulus control procedures

- Sleep hygiene recommendations

Stimulus control procedures

- Establish regular times to wake up and to go to sleep

- Avoid blue spectrum light from TV, smart phones, computers, and tablets

- Avoid day time naps

Sleep hygiene recommendations

- Exercise routinely, but not close to bedtime

- Create a comfortable sleep environment by avoiding temperature extremes, loud noises, and illuminated clocks in the bedroom

- Discontinue or reduce the use of alcohol, caffeine, and nicotine

OTC Products

- Antihistamines

- Diphenhydramine and Doxylamine

- Block both H1 and muscarinic receptors

- MILD insomnia

- AVOID in elderly

Dosing Strategies

- Increased Dose ≠ Increased Response

- Consider use for 3 days with an “off” night to reduce

- Should NOT be used for more than 7-10 consecutive nights

- Lower doses required for those with hepatic cirrhosis

Supplements

- Melatonin

- Valerian Root

- Kava

Prescription options

- Benzodiazepines

- Nonbenzos

Benzodiazepines

- Long-Acting Benzodiazepines

- Intermediate-Acting Benzodiazepines

- Short-Acting Benzodiazepines

Long-Acting Benzodiazepines

- Flurazepam

- Quazepam

- Half Life >24 hours

- Daytime sedation, psychomotor incoordination, and cognitive deficits

Intermediate-Acting Benzodiazepines

- Temazepam

- Estazolam

- Half Life of 6-24 hours

- Daytime sedation, psychomotor incoordination, and cognitive deficits

Short-Acting Benzodiazepines

- Triazolam

- Half life <6 hours

- Anterograde amnesia more likely to occur

SE of Benzodiazepines

- Dose dependent

- Tolerance after one month

• Anterograde Amnesia: impairment of memory/recall of events after taken dose

• Rebound Insomnia: increased wakefulness beyond baseline, last a few nights after abrupt discontinuation

• Prolonged sedation and cognitive and psychomotor impairment are common in elderly due to drug accumulation

– BEERS Criteria

Nonbenzos

- Zolpidem, Zaleplon, Eszopiclone

- Suvorexant

- Lemborexant

- Melatonin Receptor Agonists

- Antidepressants

Zolpidem, Zaleplon, Eszopiclone

- MoA: bind to GABA A (agonist effects)

- Only sedative properties (zzzzz drugs)

- Warnings w/ sleep related activities (driving, preparing food, phone calls)

Zolpidem

- Reduces sleep latency and nocturnal awakenings and increases total sleep time

- Take on an EMPTY stomach

- SEs: drowsy, amnesia, HA, GI, weight gain (sleep eating)

Zaleplon

- Decreases time to sleep onset

- Short t ½ (1 hour) → no effects next day and may be used for middle of the night awakenings

- SE: dizziness, HA, somnolence

- DDI with cimetidine (only take 5 mg)

Eszopiclone

- Reduces time to sleep onset, wake time after sleep onset, number of awakenings and increases total sleep time and quality

- Only take for total of 6 months

- Duration of 6 hours → good option for sleep maintenance or early morning awakenin

- SEs: somnolence, unpleasant taste, HA, and dry mouth

Suvorexant

- Difficulty initiating and maintaining sleep

SEs: Somnolence, sleep paralysis (rare) , cataplexy, narcolepsy

- Use NOT Recommended: patients taking STRONG CYP3A4 INHIBITORS

Lemborexant

- Orexin Receptor Antagonist

- Used to induce sleep onset and sleep maintenance

- Side Effects: drowsiness, fatigue, HA

- Rare sleep paralysis / cataplexy

Doses:

- kinda just know women usually need less than men for effective dose

Melatonin Receptor Agonists

- Ramelteon (Rozerem®)

- Tasimelteon (Hetlioz® )

Ramelteon (Rozerem®)

- Sleep-Onset Insomnia

- Mt1 and MT2 agonist

- NOT controlled

- AVOID taking with or immediately after a high-fat meal

Tasimelteon (Hetlioz® )

- Non-24-Hour Sleep Wake Disorder

- May take weeks to months to work

- Drug Interactions: Strong CYP1A2 inhibitors and 3A4 inducers

Antidepressants

- TCAs

- Trazodone

TCAs

- Amitriptyline(Elavil), Nortriptyline (Pamelor), Mirtazapine (Remeron) and Doxepin

- SEs: adrenergic blockade, daytime sedation, weight gain, anticholinergic activity and cardiac conduction prolongation

Trazodone

- Improves sleep continuity

- Inhibits reuptake of serotonin

- Effective for patients with SSRI or Bupropion induced insomnia and in substance abuse

Evaluation of Outcomes

-After 1 Week: Assess efficacy, SE, adherence to nonpharm recs

- Keep sleep diary

- Educate on tolerance, withdrawal, rebound insomnia

- Abuse potential