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Sleep-Wake Pharmacology Outline

I. Drugs that disturb Sleep-wake

II. Drugs that promote sleepIII. Drugs that promote wake

Antidepressants

TCA-such as amitriptyline,

nortriptyline, etc.

Increase TST, PLMs,decrease REM anddecrease alertness

• SSRI– Fluoxetine, paroxetine, sertraline, fluvoxamine,

citalopram• SNRI

– venlafaxine

• Cause insomnia• Decrease total sleep time and REM• Cause PLMs

NDRI-Bupropion

• Can cause– insomnia– Vivid dreams– nightmares

SARI

• Trazadone–Improves sleep–Increases TST, SWS–Decreses SL, REM

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NASSA

• Mirtazapine (Remeron)– Improves sleep– Can cause daytime sedation

Anxiolytics• Benzodiazepine

– Diazepam,alprazolam,temazepam,clonazepam

– Help muscle relaxation– Anxiolysis– Sedation– Improve sleep– + daytime sedation

Buspirone

• Slower onset than BZD• Less daytime sedation

Cardiovascular Drugs

• Beta blockers– Insomnia, dreams, nightmares– Propranolol, timolol greater than carvedilol

and atenolol– Lipophilic greater than hydrophilic

Alpha-Agonist

• Clonidine, methyldopa– Insomnia– Nightmares– sedation

Ace Inhibitors

• No effect

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Reserpine

• nightmares

Hypolipidemic Agents

• Reported cases of insomnia withatorvastatin and lovastatin

Anti-Histamines• Benadryl

– Sedating (lipophilic)

• Terfenadine, cetirizine, loratidine– Less sedating (hydrophilic)

• Cimetidine, rantidine, famotidine– Less sedating (hydrophilic)– Increase levels of theophylline, CMZ, Beta-blockers

Steroids

• Insomnia• Inconsistent• Decreased REM• Little effect from inhaled

Theophylline

• Related to caffeine• Disturbs sleep in normal, asthma, CF,

OSAs, COPD• Peeks ~ 2 hrs• Half-life 8-9 hrs

Antiparkinsons

• Levodopa/Carbidopa– Low dose: can improve sleep– Higher doses: disrupts sleep, nightmares,

hallucinations• Dopamine Agonists

– Pramipexole, ropinerole– Increase daytime sleepiness– ?sleep attacks?

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MAOI-B

• Selegiline– insomnia

Amantadine

• Insomnia• Hallucinations• Nightmares

Antiepileptics

• Older agents caused more sedation– Dilantin, phenobarbital, valproate, mysoline,

carbamazepine• Newer agents have less sedation

– Lamotrigine, levetiracetam, zonisamide• Gabapentin can increase SWS• Lamotrigine can decrease SWS

Anorectics

• INSOMNIA• INSOMNIA• INSOMNIA

Drugs that promote sleep

• Match the drug to the problem• Sleep onset vs maintainence

Sleep Onset

• Zolpidem– po ambien, SL edular– Onset 30-60– Half life 2.5-3 hr– Ambien CR half life 4-

6 hr

• Zolpidem– SL intermezzo– WASO– Onset 30– Half life 2.5 hr

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• Doxepin (silenor)– Onset 30-60– Half life 4-6 hr

• Escopiclone (lunesta)– Onset 30 min– Half life 4-6 hr

Sonata

• Onset 30-45• Half life 1.5-2

Sleep Maintanence

• Rozerem (remelteon)– Onset 30-45– Half life 2-5 hr

BZD

• Temazepam–Onset 15-30–Half life 6-8 hr

• Clonazepam–Onset 30–Half life 8-12 hr

• Gabapentin• Barbiturates• TCA• trazadone

Melatonin

• 0.3-5mg• Insomnia-1 hr prior to bedtime• DSPS-every 6-8 hr

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Drugs to help wake

• Caffeine– Coffee 70-150mg/cup– Soda < 70 controlled– Energy ??

– Half life 5-6 hrs

Ritalin Formulations

Non Ritalins

• Provigil (modofinil), Nuvigil (armodafinil)– Onset 1-2 hr– Max 2-4 hr– Half life ~15 hr

– Take one hour prior to eating• Sleep Walking

– Non REM, SWS– Safety– BZD

• Night Terrors– Non REM– Safety– BZD?

Nightmares

• REM sleep• REM suppressants• TCA, Remeron, ventafoxine, BZD

REM Behavior Disorder

• REM without atonia• Dream enactment• Clonazepam, melatonin• Parkinsonism

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Light• Primary zeitgeber, esp blue wavelength• Drives wake-delays sleep• Delayed sleep phase• Advanced sleep phase• Shift work disorder

Electronic Intrusion

• TV, computer, cellphone, etc

Hypnogram Wake-NREM-REM

Abbreviations

• TST-Total sleep time• BZD-benzodiazepine• WASO-Wake after sleep onset• RBD-REM behavior disorder• SWS-Slow wave sleep• DSPS-Delayed sleep phase disorder