Michelle Zetoony, DO, FCCP, FACOI 545 4 th Avenue S, Suite A Phone: 727-826-0933 Fax: 727-826-0744 http://www.dosleep.com SLEEP TALK 9/9
BMJ Open2012 Pharmacology and therapeutics Research
What is sleep? What is a medication? Medications used specifically to affect sleep Medication timing and sleep Unintentional effects of medications
Complex REVERSIBLE state characterized by behavioral quiescence, as well as diminished responsiveness to external sleep. No unified theory per se. What we know is based on the following: Structure Function What happens with sleep deprivation
Total sleep time (TST) Total recording time (TRT) Sleep latency (SL) REM latency (REML) Stages of sleep Stage changes of sleep
***Substance taken for purpose of an effect.*** Short term use of medication (particularly in sleep) is defined as < 3 weeks. Chronic use is > 1 month. over $1.5 Billion dollars is spent on medication for treatment of primary sleep diagnosis Mainly insomnia which is thought to affect at least 33% of the adult population.
Why people take medications that affect sleep. Help fall asleep Help stay asleep Help stay awake Some medications are not intended to affect sleep by affect sleep.
Sedative or hypnotic medications relax upper airway tissue and muscle and may significantly worsen apnea in some patients. Medications that are used as sleep aids or those to alert during the day are NOT treatment replacements for apnea. Treating underlying sleep apnea may decrease need for medication.
INTENTIONAL, PLANNED, or EXPECTED
Sedating antihistamine Alcohol containing product. Herbal substance ** Caffeine containing products Non-caffeine stimulant products
Moderate to severe drowsiness the next day Dizziness and forgetfulness Clumsiness, feeling off balance Constipation and urinary retention Blurred vision Dry mouth and throat **Many have 8-12 hour half-lives.
Total sleep time (TST) same or increased Sleep latency (SL) - decreases REM latency (REML) same or increased Stages of sleep typically expect decreased SWS and REM in favor of more N1/N2 Stage changes of sleep unchanged EXCEPT alcohol containing, increased after 4 hours Generally no change to sleep stages with melatonin; some studies indicate increased SWS(N3) with 5-HTP.
Benzodiazepine Benzodiazepine Receptor Agonist (BRA) Melatonin Receptor Agonist Tricyclic antidepressant
Come in many products with varying halflives ranging from 1.5 to 40 hours!! Longest used. All available generic But not necessarily at all doses
Total sleep time (TST) increase or unchanged Sleep latency (SL) decreases! REM latency (REML) increases or no change Stages of sleep Increased N2 Often see presence of excess sleep spindles Stage changes of sleep decrease or unchanged
First one approved was Ambien followed by Sonata. Now many are available generic. New formulations have become available for more rapid absorption. Multiple safety and efficacy trials have been completed up to 12 weeks of therapy. Walsh et al. Sleep 2000. Vol 23. No. 8
Total sleep time (TST) increase or unchanged Sleep latency (SL) decreases! REM latency (REML) increases or no change Stages of sleep Decreased SWS/REM and often increased N2 Stage changes of sleep decrease or unchanged
There is one FDA approved for sleep (YES, ONLY ONE) Silenor HOWEVER, this is the most frequently used category of prescribed sleeping pill for the last decade. Trazodone (Desyrl???) has been #1 Many antidepressants are sedating and if patient has co-morbid depression and insomnia, appropriately timed antidepressant can be first line treatment. Relatively frequent cardiac conduction abnormalities. Highly lethal in overdose
Total sleep time (TST) variable Sleep latency (SL) variable but can decrease REM latency (REML) increases Stages of sleep Decreased SWS/REM and often increased N1/N2 Stage changes of sleep often significant increase
FDA approved for following indications Residual sleepiness despite treatment of OSA Shift work sleep disorder Narcolepsy Thought to work through the stimulating dopamine pathway in the brain Taken when patient wakes from sleep to keep more alert.
Total sleep time (TST) can decrease, particularly if taken too late in day. Sleep latency (SL) may increase/no change REM latency (REML) increases Stages of sleep May decrease REM Stage changes of sleep no change
Come in all different types ( natural, synthetic, combined) Work centrally and peripherally So increased side effects: palpitations, tremors, cardiac arrhythmia, sweating, mood change OTC and Prescribed Short, medium (sustained release) and long acting (extended release)
Total sleep time (TST) variable, often decrease Sleep latency (SL) increase REM latency (REML) increases Stages of sleep Significant decrease SWS/REM Stage changes of sleep often significant increase
These guys get into very specific issues but have a fair amount of literature Xyrem (sodium oxybate) Marijuana Cocaine
AKA: How my heart pill affects my sleep.
Obstructive sleep apnea Restless leg syndrome Periodic limb movements of sleep Cardiac dysrrhythmia Anxiety and depression Hyperhydrosis Dry mouth, dental caries Visual changes GI problems (mostly diarrhea, dyspepsia) Fertility issues
Other medications you are taking, non-prescription medications herbal supplements Prescriptions Specific instructions for decreasing and/or terminating use. Using the medications intermittently Other medical conditions you have. There are specific issues with blood pressure, liver problems, glaucoma, depression, and breathing difficulties. COMBINING MEDICATIONS CAN BE VERY DANGEROUS.
And other interesting medications that you may not think can affect sleep.
Beta blockers Insomnia Nightmares/vivid dreams Daytime tiredness and fatigue **fewest side effects seen with atenolol Alpha2 agonists (clonidine/methyldopa) Sedation (but goes away with long term use) Frequently prescribed in pediatrics with sleep prob Decreases total slseep time in hypertensive patients Methyldopa may increase REM but decrease N3 Alpha1antagonists (prazosin and terazosin) Transient sedation Calcium channel blockers, ACE-I and vasodilator (hydralazine) have not been shown to have significant direct effects on sleep.
There has been a reported amount of insomnia related to these drugs PRETTY UNCOMMON given the widespread use. Of those studied, lowest incidence with atorvastatin and lovastatin.
These medications are typically used for antiacid. RARE effects on sleep are reported Insomnia Sedation Cimetidine, ranitidine, famotidine, and Nizatidine)
Associated with the following sleep effects: Sedation Insomnia Daytime sleepiness Irresistable sleep attacks
Typically sedation When used for seizures, typically being used more than once a day. Newer anticonvulsants tend to have less sedation than older class Overall sleep effects Decrease sleep latency Increase total sleep time Tiagabine, gabapentin & pregabalin can increase N3. Lamotrigine can decrease N3.
Typically they are anorectic agents, mostly stimulants with exception of orlistat. Antiinflammatories Help sleep by decreasing pain that often decreases TST and sleep efficiency. Opioids Decrease both REM and N3. Can contribute to the development of central or complex sleep apnea
Medication review Why? Circumstances and how has that changed Evaluation of combination therapy Side effect of another medication
HOW TO RELAX and WORK ON SLEEP
Michelle Zetoony, DO, FCCP, FACOI http://www.doslee.com QUESTIONS???