Medications and Their Effect on Sleep and Sleep Disorders

LEARNING OBJECTIVES

On completion of this chapter, the reader should be able to:

1. Recognize major classes of drugs that may alter the polysomnogram.
2. Detect sleep disturbances that may occur because of specific medications.
3. Describe the relationship between sleep and medications.
4. Recognize when to intervene on behalf of patient safety.

The Center, for Disease Control and Prevention (CDC) reported in 2016 that 49% of the U.S. population used at least one prescription drug within the past 30 days; 23% used three or more prescription drugs, whereas 12% used five or more prescription drugs (1). Chances are that three out of four of the 84% using a prescription drug within the past 30 days are being seen in the sleep laboratory tonight. The purpose of this chapter is to assist the technologist to provide better patient care by understanding how daily medications can affect sleep and sleep disorders.

MEDICATIONS AND HOW THEY AFFECT SLEEP

About 89% of patients rely on some sort of prescribed medications. Most of these medications are for chronic conditions, whereas some are used for acute ailments. Medications for high blood pressure, heart disease, respiratory issues (asthma, chronic obstructive pulmonary disease), headaches, smoking cessation, colds and allergies, to name a few, can affect sleep by either depriving the patient of sleep or causing daytime sleepiness.

Some of the more commonly prescribed medications are antiarrhythmic drugs used to treat heart rhythm issues, which can cause difficulty initiating and maintaining sleep or insomnia. Beta-blockers are used to treat hypertension, arrhythmias, and angina. Beta-blockers increase the likelihood of awakenings during the night, nightmares, and/or insomnia. Cholesterol medications are associated with poor sleep. Asthma medications can cause insomnia because the chemicals in theophylline are related to caffeine and can make the patient feel fidgety. Thyroid conditions can cause tremendous sleepiness (specifically hypothyroidism), whereas the medication used to treat this disorder causes insomnia. These are a few of the common prescription medications often seen on the patient’s medication list. This chapter will review medications that can affect a patient’s sleep and the effects of medications on the polysomnography (PSG).

Hypnotics

Barbiturates

Barbiturates, sometimes called “downers,” are medications that act on the central nervous system (CNS) by depressing or inhibiting nerve signals in the brain. They work by depressing the reticular formation, a comprehensive network of nerves found in the central area of the brainstem, thus promoting sleep. Other uses include, but are not limited to, anesthesia during surgery,
an anticonvulsant, and for anxiety attacks. Barbiturates are derived from barbituric acid (2) that scientists have synthesized and are grouped according to how fast they produce an effect and how long that effect lasts, and are classified as sedative hypnotics that lead to the slowing down of the body’s functions. This slowing down of the body’s functions can include physical signs such as lethargy, slurred speech, shallow breathing, fatigue, drowsiness, and difficulty in concentrating.

Expected and possible effects on PSG (acute):

Decrease: Sleep latency (SL), wake after sleep onset (WASO), N1, rapid eye movement (REM), N3, arousals, and body movement.

Increase: Sleep efficiency (SE), total sleep time (TST), N2, spindles, N3, REM latency (RL), sleep apnea, and daytime sleepiness.

Withdrawal: Decrease TST and increase REM (REM rebound).

Barbiturates are now rarely used most likely because of the numerous adverse side effects and high incidence of tolerance and dependence. They used to be the “go-to drug” for insomnia but have lessened in popularity with the advent of benzodiazepines (BZDs).

Benzodiazepines

BZD is a psychoactive medication used as a sedative or muscle relaxant. When one suffers from anxiety or panic attacks, the brain becomes overactive and BZDs are chemicals that will help it to slow down. Although it is not clear how BZDs work, they are believed to affect the GABA receptors of the brain. GABA, or gamma-aminobutyric acid, is a major inhibitory brain chemical that blocks the transmission of a signal from one brain cell to another. Although GABA is an amino acid, it is classified as a neurotransmitter; it inhibits and relaxes, therefore inducing relaxation and sleep.

Expected and possible effects on PSG (acute):

Decrease: SL, WASO, REM, N3 (for most agents), periodic limb movements (PLMs), and arousals.

Increase: SE, TST, N1, N2, spindles, N3 (for some agents), RL, sleep apnea, and daytime sleepiness.

Withdrawal: Increase WASO, decrease TST, increase REM (REM rebound), increase SL, and arousals.

Although BZDs contain chemicals like those found in the body to induce calming, adding them to what is already in the body helps GABA receptors send out a greater number of these signals to the brain, resulting in sedation or relaxation. BZDs are also used for general anesthesia, sedation before medical procedures, alcohol withdrawal, nausea, and vomiting. Although BZDs are used for various reasons, some are more commonly prescribed for certain conditions (3):

Alcohol withdrawal: Chlordiazepoxide (Librium)

Anesthesia: Diazepam (Valium), lorazepam (Ativan), and midazolam (Versed)

Anxiety: Alprazolam (Xanax), chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), lorazepam (Ativan), and midazolam (Versed)

Insomnia: Estazolam (Prosom), flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), and triazolam (Halcion)

Irritable bowel syndrome: Chlordiazepoxide clidinium (Librax)

Muscle relaxant: Diazepam (Valium)

Seizure: Clonazepam (Klonopin), clorazepate (Tranxene), and diazepam (Valium)

Reduce PLMs: Clonazepam (Klonopin)

Keeping in mind that some BZDs have been used for a multitude of medical conditions, one should then not assume that a patient, who, for illustration purposes, takes diazepam, suffers from seizures. The sleep technologist should always take the time to read each patient’s medical history (Table 32-1).

Nonbenzodiazepine (NBZD, Z-Drugs, and GABA Receptor Agonists)

NBZD, a relatively newer class of drugs, is also used for surgical anesthesia but is more widely advertised as a short-term treatment for insomnia. These drugs work in the same area of the brain as BZDs do but tend to be more specific for inducing sleep.

NBZDs are generally known to have a shorter half-life, so it is rare to wake up with a “hangover” feeling the following day. Newer controlled-release formulations may extend the half-life of the medication as in the case of zolpidem. Information released by the Food and Drug Administration (FDA), however, states that the termination half-life for controlled-release zolpidem (12.5 mg) is no different from that of the immediate release formula (10 mg).

The use of NBZDs is less likely to cause addiction but may cause amnesia and erratic behavior (as parasomnia). One should keep in mind, however, that these medications would not address any underlying medical problems that may cause insomnia and therefore should not be seen as a cure (Table 32-2).

Other Hypnotic Agents

Two examples of hypnotic agents are ramelteon and chloral hydrate. Ramelteon is considered a melatonin receptor agonist, thus inhibiting the wake-promoting activity of the suprachiasmatic nucleus. It also helps reduce SL and increase TST, while having no effect on sleep architecture. Chloral hydrate, an alcohol-type hypnotic,

is occasionally used in the elderly. It has a short half-life (4 to 6 hours) and will decrease SL and arousals. Slow-wave sleep (SWS) is also slightly depressed, but overall REM sleep is unchanged (4).

Table 32-1 Benzodiazepines

Generic Name	Popularly Known as/Brand Name	Time to Peak (Onset of Action [h])	Elimination Half-life (h) (Active Metabolite)
Alprazolam	Xanax	1-2	6-12
Chlordiazepoxide	Librium	1.5-4	5-30 (36-200 h)
Clonazepam	Klonopin	1-4	18-50
Clorazepate	Tranxene	Varies	(36-100 h)
Diazepam	Valium	1-2	20-100 (36-200 h)
Estazolam	Prosom	0.5-5	10-24
Flunitrazepam	Rohypnol	0.5-3	18-26 (36-200 h)
Flurazepam	Dalmane	1-1.5	(40-250 h)
Halazepam	Paxipam	1-3	(30-100 h)
Lorazepam	Ativan	2-4	10-20
Midazolam	Versed	0.5-1	3 (1.8-6 h)
Oxazepam	Serax	3-4	4-15
Quazepam	Doral	1-5	25-120
Temazepam	Restoril	0.5-3	8-22
Triazolam	Halcion	0.5-2	2
Expected Effects of Benzodiazepines on Polysomnography
<	SL
>	SE
>	TST
<	WASO
>	NREM 1
>	NREM 2 > Spindles
<<	SWS
>	RL
<	REM
<	Arousals
<, >	PLMs
≥	Sleep apnea
>	Daytime sleepiness
	Withdrawal
<	TST
>	REM (REM rebound)
>	Arousals
>	SL
Expected Effect on Polysomnography
<	SL
>	SE
>	TST
<	WASO
<	NwwwwREM 1
>	NREM 2 (spindles)
≤	SWS
>	RL
≤	REM
<, >	Arousals
=	PLMs
=	Sleep apnea
	Withdrawal
≥	WASO
NREM, nonrapid eye movement; PLM, periodic limb movement; REM, rapid eye movement; RL, REM latency; SE, sleep efficiency; SL, sleep latency; SWS, slow-wave sleep; TST, total sleep time; WASO, wake after sleep onset.

Table 32-2 Nonbenzodiazepines

Generic Name	Popularly Known as/Brand Name	Onset of Action (min)	Half-life (h)
Eszopiclone	Lunesta	60	4-6
Zaleplon	Sonata	15-30	1
Zolpidem	Ambien	15-30	2-3
Expected Effects of Nonbenzodiazepines on Polysomnography
<, >	SL
<, >	SE
>	TST
<	WASO
>	NREM 2 (spindles)
≥	SWS
>	RL
<<	REM
>	PLMs
≥	Daytime sleepiness
	Withdrawal
>	WASO
>	REM
NREM, nonrapid eye movement; PLM, periodic limb movement; REM, rapid eye movement; RL, REM latency; SE, sleep efficiency; SL, sleep latency; SWS, slow-wave sleep; TST, total sleep time; WASO, wake after sleep onset.

Antidepressants

There are occasions when doctors prescribe antidepressants to promote sleep despite none of these being specifically approved as sleep medications.

Antidepressants, the third most prescribed drug in this country, were first developed in the 1950s to help relieve the symptoms of depression. Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are the two most popular on the market today (5).

Tricyclic Antidepressants

TCAs are considered a first-generation antidepressant medication and are named for the molecular structure of most of the drugs in this class. They are one of the oldest classes of antidepressants and continue to be prescribed today. They are thought to act by blocking the reuptake or reabsorption of two critical brain hormones, the neurotransmitters serotonin and norepinephrine. Some block one, some the other, and some block both.

Neurotransmitters are different types of chemical messengers that the brain contains, which act as communication agents between various brain cells. Two of these transmitters are serotonin, also known as 5-hydroxytryptamine, and norepinephrine. Serotonin’s effects are normally inhibitory. It diminishes appetite and sexual behavior and suppresses pain perception, and has also been correlated with eating and sleep disorders (6). Norepinephrine plays a significant role in how the body responds to stress. It is more involved in maintaining normal body functions such as heart rate, blood pressure, and blood sugar levels and in regulating attention, emotions, and sleep (7).

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