MEDICATIONS AND THEIR EFFECT ON SLEEP ARCHITECTURE
Marianne J Davey MSc, Director, British Snoring & Sleep Apnoea Association
‘WHAT PROBING DEEP HAS EVER SOLVED THE MYSTERY OF SLEEP?’
Thomas Bailey Aldrich
Sleep patterns vary from one individual to another, some need only 4-5 hours and others may need
10-12, but in general, adults sleep for about 7-8 hours per night. It is estimated that we spend
around one third of our lives asleep and our day-to-day well-being is often measured by our
perceived sleep quality. Approximately 35% of the
population suffers from insomnia but only about 5% of
Sleep is divided into two distinct states — Rapid EyeMovement (REM) sleep and non-REM which is furtherdivided into 4 stages: Stage 1 (drowsiness), Stage 2(light sleep), and Stages 3 & 4 (deep sleep). Deepsleep is often referred to as slow-wave sleep (SWS).
These stages of sleep alternate in 70 - 90 minutecycles and in an average night, sleep will move through4 to 5 cycles. See Figure 1.
However, many individuals rarely obtain a good night’s sleep. Sleep disturbances can be classifiedaccording their duration as either transient (<1 week), short-term (1-3 weeks) or chronic (months).
Additionally they can be a primary disorder or occur secondary to other disorders. Here we willbriefly examine the sleep disturbances caused by a range of prescription and over-the-counter(OTCs) medications and also discuss how some
lifestyle choices can have a detrimental effect onour sleep.
‘PAIN IS THE ROOT OF KNOWLEDGE’
Pain is probably the most frequent and disabling symptom in medicine. It causes sleep deprivation
which can further worsen the severity of the pain. Studies have reported greater sleep disturbance
among patients with acute or severe pain and can predict the level of sleep disturbance to the
severity of pain(11).
Analgesics used in the symptomatic treatment of pain can be broadly divided into 3 categories:opioids, nonopioids and adjuvant analgesics(14).
Opioids include heroin, morphine, methadone and codeine. They are used as major analgesicsand are known for their sedating effects but they also have a profound effect on sleep disturbance.
Known disturbances include prolonged sleep latency (SL), decreased SWS and REM, and and anincrease in arousals throughout the night. Opioids are also known to depress respiratory drive bydecreasing the respiratory centre’s sensitivity to carbon dioxide(3,14). Kosinski in his study, evaluatedthe changes in pain and pain-related sleep disturbance with the use of Tramadol. Paradoxically,despite somnolence and insomnia being the most commonly cited adverse events, patientsreported significant improvement in their pain-related sleep disturbance(11).
Nonopioid analgesics are generally known as nonsteroidal anti-inflammatory drugs (NSAIDs) thatinclude paracetamol, aspirin and ibuprofen. In a study by Onen, paracetamol had a beneficialeffect on sleep quality even in patients free of pain, whereas aspirin and ibuprofen had a negativeeffect (increased SL, increased awakenings, decreased SWS). However, Genco in his study,treated healthy subjects with 400mg ibuprofen TID for 3 days, and reported no interference in sleeppatterns.
Adjuvant analgesics comprise those drugs that have a primary indication other than pain but arealso known to be analgesic in some circumstances. These analgesics usually includeantidepressants and anticonvulsants. Although antidepressants supress REM sleep, induce morerestless sleep, and sometimes worsen insomnia, according to Lam(12) they objectively andsubjectively improve quality of sleep in depressed individuals.
‘PEOPLE WHO SAY THEY SLEEP LIKE A BABY USUALLY DON’T HAVE ONE’
Benzodiazepines,are among the most commonly prescribed hypnotics. As well as affecting sleep
architecture they can have an adverse effect on breathing during sleep. These medications are
mild respiratory depressants and can increase the apnoea/hypopnoea index and decrease oxygen
saturation. Brown’s study found the mean number of apnoeas increased from 5/hr on a control
night to10/hr on the drug night with oxygen desaturation. This effect is more pronounced in those
individuals who suffer from sleep disordered breathing (SDB).
Antidepressants are prescribed for mood disorders but they are sometimes prescribed for use ashypnotics. In polysomnography (PSG) studies antidepressants were found to suppress REMsleep, increase awakenings and arousals and reduce total sleep time (TST)(6). There is also thetendency to exacerbate periodic limb movements during sleep and restless leg syndrome(3).
Symptoms of sleep abnormalities have been reported to occur in around 60-80% of depressedpatients but there have been mixed reports on the use of antidepressants. In one study,improvements in both SL and TST were demonstrated(6). However, in Wilson’s study, only anincrease in REM onset latency was reported(17).
‘PEOPLE WHO SNORE ALWAYS FALL ASLEEP FIRST’
The use of medications for the treatment of sleep disordered breathing is theoretically attractive.
Compared with current treatments (Mandibular Advancement Therapy, CPAP), compliance would
improve dramatically if patients simply had to take a daily pill. The use of ventilatory drive
stimulants, central nervous system stimulants, antidepressants, serotonin reuptake inhibitors or
antagonists, antihypertensive agents and even sedative hynotics agents have been studied but no
data has demonstrated that pharmacologic agents improve upper airway muscle activity(9). Indeed
studies have shown that sedatives have a deleterious effect on respiration during sleep, reduced
genioglossal muscle tone — with consequent worsening of Obstructive Sleep Apnoea (OSA),
increased apnoeas and increase in severity of nocturnal oxygen desaturation(9,13). Lu in his study,
found some of the physicians (who did not usually treat patients with sleep disorders) prescribed
sedatives to patients with undiagnosed OSA who presented with sleep related symptoms. Of the
50 physicians in the study, only one third of them screened their patients for OSA prior to
THE BIG 3 — CHALLENGES OF MODERN LIFE
Caffeine is without question the most commonly used stimulant world-wide, with an estimated
mean consumption of 210-238mg per person per day(3,7). PSG studies demonstrate the most
prominent effects of caffeine to be prolonged SL, reduced sleep efficiency, reduced SWS and
increased awakenings during sleep.
Alcohol is the second most commonly used psychoactive substance used world-wide(3). Anestimated 13% of of people use alcohol as an aid to sleep. It is similar to sedative hypnotics andhas significant effects on sleep. One study reported alcohol users to suffer decreased SL,suppressed REM sleep (dose-dependent) and increased excessive daytime sleepiness,significantly more than nonusers. The authors concluded that continued use of alcohol as a sleepaid exacerbates these disturbances(10). The effect of alcohol in alcoholics is different. SL and TSTis decreased and their sleep is composed primarily of non-REM sleep. Even after more than 2
years of abstinence, recovering alcoholics show abnormal sleep patterns. Alcohol decreasesmuscle tone, particularly in the upper airway and leads to the development or worsening of snoringand OSA. It decreases the arousal response so that obstructive events become longer in duration.
Nicotine affects sleep both during use and on withdrawl. PSG studies show that compared to non-smokers, current smokers experience increased SL, less TST and lower sleep efficiency.
Additionally, a drop in nicotine levels in the brain during sleep causes nicotine craving(19). This stateof withdrawl modifies sleep continuity and subjective results showed smokers experience moredifficulties with morning wakefulness and EDS than non-smokers. Cessation of smoking canreverse these conditions.
‘HE SLEEPS WELL WHO IS NOT CONSCIOUS THAT HE SLEEPS ILL’
Insomnia (specifically increased SL) is a common complaint of persons using illicit drugs,
although withdrawl from the drug itself can also induce a variety of sleep problems. Increased TST
and REM sleep occur during initial abstinence followed by persistent insomnia and REM
disturbance for several weeks after. For some, sleep disturbance is so severe it can inhibit
treatment success with consequent relapse to addiction(3,15).
In asthma and allergic rhinitis inflammation increases at night often leading to disturbed sleep. Theuse of antihistamines and decongestants is common but the side effects of these medications cancause insomnia and subsequent daytime fatigue(18).
Patients with Alzheimer's disease (AD) commonly have poor sleep and a high incidence of SDB.
Sleep disturbance in AD may be multifactorial and involve SDB and disrupted chronobiology oftencharacterised by excessive daytime napping(1). In a study by Cooke(4), PSG results demonstratedthat AD patients with SDB spent less of the night in REM sleep than those with no SDB, but therewere no differences in other sleep stages. In a further study by Cooke(5), it was found thatAcetylcholinesterase Inhibitors (AChEls) used in AD, changed sleep architecture significantly.
There were changes to stages 1 & 2 sleep, but no changes to REM or SWS. A betterunderstanding of the cause-and-effect relationship of AChEls is needed to further understand theireffects on sleep architecture. Meanwhile treating these patients’ SDB may improve their daytimefunctioning.
‘SLEEP IS THE GOLDEN CHAIN THAT TIES OUR HEALTH AND BODIES TOGETHER’
Although the effects of a drug are known, some medications may act differently in individuals who
are more susceptible to sleep related problems. Screening patients for substance use/abuse,
SDB and self-medication with OTCs will provide useful information when patients present with
sleeping difficulties. The Epworth Sleepiness Scale (ESS) is a simple and efficient test to
determine the degree of daytime sleepiness. Patients with a high ESS and a BMI >25 are at risk of
sleep disordered breathing(2).
Mrs Marianne J Davey MSc, DirectorBritish Snoring & Sleep Apnoea AssociationCastle Court, 41 London Road, Reigate, RH2 9RJTel: 01737 245638 Fax: 0870 052 9212email: [email protected]
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4. Cooke JR et al (2006) Acetylcholinesterase inhibitors and sleep architecture in patients with Alzheimer’s disease.
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7. Drapeau C et al (2006) Challenging sleep in aging: the effects of 200mg cafeine during the evening in young andmiddle-aged moderate caffeine consumers.
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8. Gengo F (2006) Effects of Ibuprofen on sleep quality as measured using polysomnography and subjectivemeasures in healthy adults.
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11. Kosinski M et al (2007) Pain relief and pain related sleep disturbance with extended release Tramadol inpatients with osteoarthritis.
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12. Lam R (2006) Sleep disturbances and depression: a challenge for antidepressants.
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13. Lu B et al (2005) Sedating medications and undiagnosed OSA: Physician determinants and patientconsequences.
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14. Onen H et al (2005) How pain and analgesics disturb sleep.
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15. Teplin D et al (2006) Screening for substance use patterns among patients referred for a variety of sleepcomplaints.
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16. Verster J et al (2004) Residual effects of sleep medication on driving ability.
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17. Wilson S et al (2002) Effects of 5 weeks of administration of fluoxetine and dothiepin in normal volunteers onsleep, daytime sedation, psychomotor performance and mood.
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18. Woods L & Craig T (2006) The importance of rhinitis on sleep, daytime somnolence, productivity and fatigue.
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19. Zhang L et al (2006) Cigarette smoking and nocturnal sleep architecture.
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BANISHING THE DARKNESS OF DEPRESSION Due to advances in medication, depression is now more treatable than many physical illnesses. However, only one out of three seriously depressed people ever seeks help! Although counseling can teach thinking and people skills that improve mood, the need for medication should be addressed first. The more of the following conditions that are present, the
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