Chapter 67. Sleep Disorders

What constitutes a diagnosis of chronic insomnia?

Symptoms 3x per week for at least three months

What is the preferred treatment for chronic insomnia?

CBT (sleep hygiene)

Select Drugs that Can Worsen Insomnia

• Acetylcholinesterase inhibitors (e.g. donepezil)

• Alcohol

• Aripiprazole

• Atomoxetine

• Bupropion

• Caffeine

• Decongestants (e.g. pseudoephedrine)

• Diuretics (d/t nocturia)

• Fluoxetine (if taken late in day)

• Nicotine (including NRT)

• Integrase strand transfer inhibitors (INSTIs)

• Steroids

• Stimulants (e.g. methylphenidate, phentermine)

• Varenicline

Natural products used for insomnia

• Melatonin

• Kava - hepatotoxicity; not recc.

• Valerian - hepatotoxicity; not recc.

• Chamomile tea

Drug Treatment to Address Sleep Problem

Falling asleep

• Eszopiclone

• Zolpidem

• Ramelteon

• Zaleplon

Staying Asleep

• Eszopiclone

• Zolpidem

• Doxepin

• Suvorexant

Both

• Eszopiclone

• Zolpidem

What can patients use that is OTC for short-term insomnia?

diphenhydramine, doxylamine (first generation antihistamines)

Hypnotics MOA

act selectively at BZD receptors to increase GABA

What DEA schedule are hypntoics?

C-IV

Which Hypnotic comes as an SL tablet?

Zolpidem (Edluar)

IR/ER tablets = Ambien, Ambien CR

Eszopiclone brand name

Lunesta

Warnings/Side effects of Hypnotics

• Additive when used with other sedating drugs (pain meds, muscle relaxants, antihistamines, mirtazapine, trazodone, and alcohol)

• CNS depression

• Potential for abuse and dependence

• Somnolence, dizziness

• Ataxia

• Headache

• Preferred over BZDs d/t less dependence/tolerance

Orexin receptor antagonists, such as daridorexant or lemborexant, block the _______________ neuropeptide signaling system, resulting in drowsiness.

BLOCK Orexin

Side effects: somnolence

Melatonin receptor agonists, such as ramelteon or tasimelteon, are not a controlled substance and act at _____________________ receptors.

MT1 and MT2 melatonin receptors as agonists; NOT a controlled substance like the other drugs

How do TCAs promote sleep?

Block acetylcholine and histamine which contributes to somnolence. Doxepin (silenor) is commonly used

Side effect: seizures

Doising of Ambien, Edluar (Zolpidem)

• Female/Older adult = 5 mg QHS

• Male = 5-10 mg QHS

Benzodiazepines enhance _________, causing CNS depression. Which one is FDA-indicated for insomnia?

GABA; Temazepam (Restoril) C-IV

Boxed Warnings: use with opioids (sedation, resp depression, death), abuse/misuse/addiction risk, physical dependence risk - taper to avoid withdrawal

• Side effects: drowsiness, dizziness, increased fall risk, cognitive impairment

Anthistamines

Block H1 histamine receptors

• Diphenhydramine (Benadryl)

• Doxylamine (Unisom SleepTabs)

Side effects: sedation, peripheral anticholinergic side effects (dry mouth, urinary retention)

Which disease states should antihistamines be avoided in?e

BPH, glaucoma

What is the primary treatment for RLS?

Dopamine agonists

• Pramipexole and ropinirole

• Rotigotine - patch

• XR Gabapentin enacarbil (Horizant) is approved for RLS

What is excessive daytime sleepiness with cataplexy (sudden loss of muscle tone)

Narcolepsy

What are the treatments for narcolepsy?

Stimulants

• Modafinil

• Sodium oxybate

• ADHD meds (dextroamphetamine, dextroamphetamine/amphetamine, methylphenidate)

What is the main side effect of stimulants like Modafinil?

Rash - can be life threatening

Which drugs are derived from GABA and are only available through a REMS d/t having an rapid onset and being used illicitly for sexual assault.

Sodium oxybate C-III (different from other Z drugs which are C-IV)