Sleep Disruptions: Overview and Treatment

Sleep is essential for life and optimal health. However, despite the importance of sleep, about 70 million Americans have significant and chronic disruptions that affect their activity and health. A 2014 survey conducted by the National Sleep Foundation reported that 35% of American adults rated their sleep quality as “poor” or “only fair” (2). Poor sleep or inadequate sleep is one of the most common complaints of my patients. We all know sleep is important but sleep is still definitely not completely understood. 

There are two types of sleep: Non-REM sleep and REM sleep. Non-REM sleep is composed of four sleep stages. The stages have been defined on the basis of physiologic parameters (i.e. muscle movements and eye movements) and changes in the frequencies and amplitudes of an EEG (electroencephalogram). 

Stage 1 Sleep : there is muscle tone present in the skeletal muscles and breathing occurs at a regular rate. 

Stage 2 Sleep : You are deeper in sleep and less able to be awakened and shows “saw tooth waves” and sleep spindles on EEG.

Stage 3 & 4 Sleep : AKA Deep Sleep: These stages are progressively deeper and are also known as “slow wave sleep” or delta sleep. A sleeper in these stages is always difficult to awaken. As we get older, humans spend less time in slow wave sleep and more time in Stage 2 sleep. These stages are believed to be the most restorative stages of sleep. 

Stage 5 Sleep AKA REM Sleep: This stage of sleep is associated with dreaming. It is very different than other stages due to EEG waves but also that the skeletal muscles have little to no tone or movement, the breathing is more erratic, heart rate increases, motor and sensory areas of the brain show more activity and the eyes move rapidly (hence the term rapid-eye movement or REM sleep). 

The Sleep-Wake System is thought to be regulated by two major processes. One that promotes sleep (Process S) and one that maintains wakefulness (Process C). the need for sleep grows throughout the day and peaks just before you sleep while gradually decreasing during sleep. Process C is regulated by the circadian rhythm and counteracts the Process S, promoting wakefulness and alertness. Without Process C, the total sleep required remains the same but is randomly distributed throughout the day rather than separated into sleep and wake episodes. 

This refers to the daily rhythms in physiology and behavior. Circadian rhythms control the sleep-wake cycle, physical activity, food consumption, body temperature, heart rate, muscle tone, and hormone secretion. Structures in the hypothalamus of the brain are responsible for circadian rhythms. Animals appear to have an internal clock to help determine daily behavior and rhythms but the external day-night cycle is also largely influential on these behaviors. In mammals, there are specific genes that are essentially turned on and off in a cyclical pattern that is very close to 24 hours (1). 

Infants and Young Children 

Newborns sleep 16-18 hours per day and the sleep is evenly distributed across the day. Circadian rhythms begin to form around 2-3 months, allowing sleep to be more consolidated into episodes during the day and night. These first 2-3 months are when melatonin and cortisol begin to cycle in patterns. Children gradually require less sleep. This is also likely influenced by social cues such as the elimination of naps etc. 

Adolescents

Most adolescents require 9-10 hours of sleep per night but a considerable amount of adolescents are sleep deprived. Although not popular among teens, a relatively fixed bedtime can help to anchor REM sleep and help to prevent sleep deprivation. 

Adults

Typically, adults develop earlier wake times and reduced sleep consolidation (1). Adults over age 65 have an average wake time that is 1.33 hours earlier and bedtime 1.07 hours earlier than young adults (1). Older adults have a higher risk of sleep disruption and sleep difficulty. Older adults do show a decrease in melatonin levels. Also, as we age, we are actually more easily awakened during Non-REM sleep as well, which means our sleep is more easily disrupted by minor environmental changes.

There are about 100 sleep disorder classifications, but for our purposes we will look at them in three categories:

In healthy individuals, short-term consequences include a heightened stress response; pain; depression/depressed mood; anxiety; and altered cognition, memory, and performance deficits . When sleep is disrupted, levels of norepinephrine and epinephrine increase indicating activation of the sympathetic nervous system. Over time this can be not only harmful to the quality of life but also may lead to certain diseases and even increase the risk of death (2).

Long-term sleep deprivation can significantly alter hormone production and release. Chronic sleep disruption is associated with adrenocorticotropic hormone (ACTH) and cortisol. Chronic sleep deprivation is also associated with decreased insulin sensitivity, therefore increasing your risk of type 2 diabetes. Decreased leptin and increased ghrelin can lead to increased appetite. In addition, sleep disruption leads to changes in pro-inflammatory cytokines such as tumor necrosis factor (TNF) and C-reactive protein (CRP). Higher sleep disturbance scores have also been associated with higher risk of elevated cholesterol, higher body mass index (BMI), and increased risk of hypertension. There is also evidence that long-term sleep deprivation can increase risk of certain types of cancer and even overall risk of death. (2)

There are many prescription medications used for sleep. In the interest of time, I will only mention the most common prescription medications used for sleep. 

Benzodiazepines (clonazepam, diazepam, alprazolam, triazolam, temazepam etc.)

There are several types of benzodiazepine medications and some have been used for the treatment of sleep and anxiety for decades. These medications bind to and activate the GABA receptor. They all have sedating effects. They all also have significant addictive and abuse potential. In addition, these medications can interact poorly with alcohol leading to dangerous changes in blood pressure and breathing. 

Benzodiazepine Receptor Agonists

Zolpidem (Ambien), and eszopiclone (Lunesta) were developed in order to selectively bind to certain GABA receptors to help induce sleep while attempting to minimize the abuse and dependence potential of the benzodiazepine medications. These medications are very effective but still have significant risk of adverse effects. My recommendation is that these medications should only be used for short periods of time to help with short-term insomnia. The biggest potential adverse effects of these medications are that they can persist into the next day and can lead to potentially dangerous situations such as driving while still under the effects of these drugs. In 2013, the FDA recommended that clinicians use lower doses of zolpidem due to blood levels staying elevated the next morning. 

Several older anti-depressants have sedating effects. The agents most commonly used for sleep are: Trazodone, Amitriptyline, Doxepin, and Mirtazapine. These medications have common adverse effects of dry mouth, dizziness, and next day drowsiness. I personally prescribe these medications only in limited cases such as patients who have failed other agents or those who have depression. 

Antihistamines  

Many antihistamines have sedating properties and are commonly used as sleep aids. Diphenhydramine is one of the most common OTC sleep aids and is found in brand name products such as Nyquil ,Z-quil, Tylenol PM, Advil PM and many others. Doxylamine is found in Unisom products. Unfortunately, these products are frequently overused, can rapidly lead to tolerance, and carry several possible adverse effects. My opinion is that these agents should never be used as sleep aids. These medications can reduce the quality of sleep, cause residual drowsiness the following day and can also cause dizziness, dry mouth, constipation, confusion and other adverse effects. Older adults are even more susceptible to these side effects and antihistamines can lead to falls during the night. Again, myself and most experts recommend against using antihistamines for sleep. (3)

Melatonin

Melatonin is a hormone produced in the brain in preparation for sleep so it makes sense that taking a supplement of melatonin could help with sleep. My main issue with this is that, for most people, a physiologic dose of melatonin would be in the 0.3-1.0mg range but most supplements contain doses 10x higher in the range of 3-10mg of melatonin, which leads to elevated melatonin levels the following day and resulting drowsiness. (3)

Valerian  

Valerian is an herbal product consisting of Valeriana officinalis . Valerian root has been used as a sleep aid since ancient Rome. Some studies show efficacy while others show minimal effects. My opinion is that Valerian can be helpful when combined with other ingredients but is not likely to be effective alone. 

Magnolia

Magnolia is an herbal supplement isolated from Magnolia officinalis and has been used in Chinese medicine for over 2000 years for a variety of issues. 

L-theanine

This is an amino acid that is used for anxiety, improved focus, and sleep. I frequently recommend this for my patients with anxiety or during times of increased stress. L-theanine is safe and is very useful for sleep, anxiety, and stress but not always effective when used alone for sleep. 

In my opinion and experience, the effectiveness and adverse effect of sleep aids vary significantly between individuals. For this reason, I am frequently researching sleep aids and we carry several options in our clinic for our patients. Below are my favorite sleep aids in no particular order. 

Sleep (Farmakeio): 5HTP, Valerian, Magnolia, phenylbutyric acid, and 5mg melatonin for those who need more melatonin

Best Rest (Pure Encapsulations): passion flower, Valerian, GABA, L-theanine, lemon balm, chamomile, 1mg melatonin, vitamin B6

Seditol Plus (Douglas Laboratories): magnolia, ziziphus spinosea, chamomile, passion flower, lemon balm extract

Insomnitol (Designs For Health): GABA, 5HTP, vitamin B6, L-theanine, and 1.5mg melatonin – these are available in chewable or capsule form.

Sleep hygiene refers to environmental and behavioral conditions intended to promote sleep. If you are having difficulty sleeping, you should definitely follow good sleep hygiene habits. This is not an exhaustive list but does include several helpful tips.

Summary

As we have discussed, sleep deprivation can lead to detrimental changes in memory and cognition, mood, and even increase the risk of depression, diabetes, obesity, heart disease and death over time. My preference is to avoid prescription sleep aids when possible and certainly to avoid antihistamines such as Benadryl (Tylenol PM etc.). I also prefer to keep the melatonin dose as low as possible. We are constantly researching new and safer sleep aids as there can be a lot of individual variation in the response to these supplements. Please let us know if you have any questions. 

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