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Relevium

HYPNOS SYNERGY

You have been diagnosed with insomnia.  Your doctor has prescribed Sleep Synergy for your condition.  Be sure to take your time and read everything below. It is essential for you to understand the potential risks and benefits of treatment. Please do not hesitate to reach out to our medical support team if you have ANY questions.  The following represents a plan that details how you can improve your sleep and optimize your sleep cycle.  This medication works for the vast majority of patients and it usually does so without causing side effects—and that’s great. However, if a trusting relationship is to work, then it must be open, meaning that we must share more than how everything can go according to plan.  Sometimes, the plan doesn’t work. It is part of the reality that no drug is a magic bullet. And, just as no drug works on everyone, no drug is 100% safe. It is important that you learn as much as you can about your treatment.  The more you read, the more questions will be answered and the better the plan can work.  Telemedicine has the advantage of convenience, but it relies on your honesty and involvement in the process. That includes reading everything below carefully (including the package insert, now online, and when it arrives in print with your medication), and communicating with your doctor. If your health should change, should you have a side effect, should the medicine not work or stop working with time, should you be prescribed ANY new medication or change your medication regimen, should you visit another doctor, please contact us.  Keep EVERY healthcare provider informed.  We are here for you. You’ve taken a big step and you are not alone. Read, learn, and ask us questions. We have done the legwork and put together information so you can do it right.  First, you read your plan, which is followed by information about insomnia.  Lastly, read the detailed information about the medication prescribed by your doctor. Read it all, and read the package insert and the official prescribers’ digital reference (PDR).  Being fully informed is the only way for you to know if this plan suits your needs and if you want to accept it as presented. You may reject it or you may want to request a modification to the plan. Please, do not hesitate to make your voice heard. Contact us with any questions. We want the best for you and the only way to do that is if you are fully informed and if we work as a team.

The prescription medicine we are giving you to help with your sleep issues is a compounded formula with multiple ingredients called Sleep Synergy.  There are different versions of Sleep Synergy, depending on your need.  The usual effective dose of Sleep Synergy is 1-3 capsules about an hour before bedtime.  The recommended starting dose is one capsule taken by mouth approximately one hour before desired bedtime.  When starting Sleep Synergy, it may take several sleep cycles to notice an improvement in sleep quality.  It is typical to see maximum improvement within a few weeks of initiation.  If (1) capsule is inadequate for treating your insomnia, increase to (2) capsules at bedtime.  If (2) capsules are ineffective, increase to (3).   Talk to your doctor if deciding to stop medicine and if tapering off the medicine is necessary. We’ve asked you about your medical history and the medicines you take to determine if it’s safe and appropriate to prescribe Sleep Synergy to you.  Make sure you read all the information below as well as the information that comes with the medicine itself. It contains important details about the risks of taking the medicine.  Only by knowing the risks and alternatives can you make an informed decision about whether you want to accept our treatment plan.  When starting Sleep Synergy, common side effects may include mild nausea or loose stools. Usually these symptoms will gradually improve over 2 weeks. These side effects may occur if taking the medicine on a daily basis.  

The ingredients of Sleep Synergy are as follows:

Doxepin – found in Sleep-D Synergy and Sleep-D Synergy Forte, at higher doses this tricyclic medication acts as an antidepressant, but at the low doses found in this compound it preferentially binds to and blocks histamine receptor sites where it exerts its sleep maintenance effect.

Trazodone –  found in Sleep-T Synergy and Sleep-T Synergy Forte this antidepressant medication increases serotonin in the brain by preventing its reuptake and subsequent breakdown in brain cells and acts as an antagonist at 5-HT-2A/2C serotonin receptors. At low doses, trazodone appears to act as a serotonin antagonist and at higher doses as an agonist.  It causes drowsiness and does appear to have slight muscle relaxant properties, but no anticonvulsant activity, and is helpful in individuals with insomnia and other sleep disorders.

Melatonin – a derivative of tryptophan, this neurohormone is produced in the pineal gland during the dark hours of the day-night cycle and binds to receptors (MT1, MT2, MT3) that coordinate the sleep-promoting properties associated with circadian rhythms.  It has also been found to increase levels of anti-inflammatory interleukins and down-regulates proinflammatory cytokines.  Prolonged administration of oral melatonin has reportedly induced phase-setting effects on circadian rhythms, such as the sleep-wake cycle and rest-activity.  It has been reported to produce reentrainment of circadian rhythms after time zone shifts, and entrainment of previously free-running rhythms in the blind.

Valeriana Root extract – Valerian extract is obtained from the roots of Valeriana, a common herb native to both Europe and Asia and now growing in most parts of the world.  Valerian root, and particularly valerenic acid, allosterically modulates GABA receptors as the basis of its anxiolytic and sedative properties.  Valerenic acid has demonstrated spasmolytic potential and central nervous depressant activity.  It is believed that valerian’s sedative effect is caused by a combination of depression of specific centers of the CNS and by direct relaxation of smooth muscle and that the most likely active components, contained within valerian, are the valepotriates, the essential oil components, and unidentified water-soluble components.  Valerian has demonstrated weak anticonvulsant effects, mild sedative and tranquilizing effects, and a spasmolytic effect.  While numerous studies have shown that valerian extract possesses mild sedative and tranquilizing characteristics, the mechanism of action for this effect has not been clarified.

Phenibut – a nootropic and GABA analogue, this molecule crosses the blood brain barrier better than endogenously produced GABA.  It is known to reduce tension, relieve symptoms of anxiety and fear, helps in the treatment of alcohol withdrawal, is useful with insomnia, and eases post-traumatic stress and obsessive compulsive disorder.

Theanine – an amino acid found in Green Tea that promotes a calm, relaxed state. It has anti-inflammatory and protective effects in the brain, stomach, and liver and may be converted into the primary inhibitory neurotransmitter GABA.

Magnesium glycinate – At least 300 enzymes dependent upon magnesium for normal functionality, including enzymes involved in neurotransmitter synthesis.  Neurons require adequate magnesium to prevent excessive excitation by calcium, which if unchecked may result in depression and anxiety-like behavior.  The glycinate moiety supports a relaxed state by serving as an inhibitory neurotransmitter.

Potassium chloride – an important mineral required for the maintenance of the excitatory properties of neuromuscular tissues and is necessary for the induction of sleep in mammalian species.  The concentration of potassium and sodium across the cell membrane regulates the excitability of the cell, nerve impulse conduction and body fluid balance.

Niacinamide – vitamin B3 that serves as an antioxidant, Niacin is involved in a wide range of biological functions such as energy production, signal transduction, gene expression and neurotransmitter synthesis and catabolism.  It is a precursor molecule that helps to form NAD+ which is important in many metabolic reactions including DNA, fatty acid synthesis, and numerous oxidation-reduction reactions.

Cholecalciferol – this vitamin facilitates the maintenance of normal calcium and phosphate concentrations via intestinal calcium and phosphate absorption, mobilization of calcium from bone, and reduction of calcium and phosphate excretion in the kidneys.  It is also implicated in the biosynthesis of neurotrophic factors, contributing to neuroprotective pathways with increased glutathione and reduced NO, and involvement in neurotransmitter synthesis including acetylcholine and catecholamines.  Exact mechanisms for most effects have not been clearly defined.  The most active metabolite, calcitriol, binds with cytosolic target-cell receptors, with subsequent interaction of the receptor complex with DNA to enhance or inhibit gene transcription.

Ziziphus spinosa seed extract – Ziziphus (sometimes spelled Zizyphus) spinosa or Z. jujuba is a small tree, commonly called jujube or Chinese date. The fruits are edible, and dried fruits and seeds are also used in Chinese medicine, often to treat anxiety or insomnia.    The seed contains betulin, betulic acid, the glycosides jujuboside A and B, several peptide alkaloids named sanjoinines, and daechu alkaloids, which contain a phenanthrene radical.  An in vitro study found that several jujubosides from Z. spinosa inhibited histamine release.  It exerts a range of sedative and hypnotic actions mediated primarily by the GABA system. Through its modulation and enhancement of the activity of GABA, this herb offers sedative effects.

Magnolia officinalis bark extract – Magnolia bark extract, produced from the bark of Magnolia officinalis, has been used as a muscle relaxant based on the properties of two of its active constituents, magnolol and honokiol. Magnolia bark modulates GABA, cannabinoid, and adenosine receptor activity and subsequently reduces anxiety levels.  Honokiol and dihydrohonokiol, the two main actors, are described as having anxiolytic actions, and subsequent alterations in serotonin turnover in different regions of the brain that results in sleep-promoting effects.  Magnolol also inhibited lipid peroxidation and protected sperm from the peroxidation damage associated with ferrous sulfate #1798 in vitro.

Moringa oleifera leaf powder – a highly nutritious plant, it exerts a central inhibitory effect by increasing glutamate and serotonin in the prefrontal cortex and decreasing dopamine and norepinephrine in the cerebral cortex, midbrain, and cerebellum.  Moringa is a significant CNS depressant that improves sleep and decreases muscle cramps.  The leaves and seeds are high in protein and vitamins. 

ADMINISTRATION Take one to three capsules by mouth about an hour before bedtime as directed by your practitioner.  Avoid drinking alcohol when taking this medicine.  Only take the medicine as prescribed.

ADVERSE REACTIONS Be sure to talk with a doctor before starting any new medicines that might interfere with your current ones. If any aspect of your health changes, please make sure to review the medicines you take with a professional. Feel free to contact us any time by sending a secure message. We typically respond within 24 to 48 hours. Depending on your response to treatment, there may be a time we recommend that you see a doctor or psychiatrist in person rather than using our service. 

COMMON SIDE EFFECTS

  •       Constipation
  •       Diarrhea
  •       Indigestion
  •       Flatulence
  •       Nausea
  •       Vomiting
  •       Dizziness
  •       Headache

UNCOMMON/RARE SIDE EFFECTS  Important warning signs of uncommon or rare side effects are listed below.  Pay close attention to any of the side effects in the list below and send us a message if any occur.

  •       Flushing
  •       Hepatotoxicity
  •       Changes in behavior
  •       Eye pain
  •       Vision changes / Blurred vision / halos
  •       Fast, pounding heartbeat
  •       Feeling nervous, anxious, irritable or excited
  •       Seizures or tremors
  •       Confusion
  •       Hallucinations
  •       Unusual bleeding or bruising
  •       Dry mouth
  •       Serotonin syndrome
  •       Heart rhythm problems 
  •       Low sodium levels
  •       Fever
  •       Sweating
  •       Muscle spasms
  •       Weakness
  •       Fainting
  •       Painful, prolonged erection of penis
  •       Trouble sleeping
  •       Tachycardia
  •       Pruritus
  •       Reduced body temperature
  •       Altered sleep patterns
  •       Bloody or black, tarry stools
  •       Throat pain, as if pill is stuck.
  •       Dark urine or pale stools
  •       Loss of appetite
  •       Depression

EMERGENT SIDE EFFECTS  Important warning signs of these severe side effects are listed below.  If you have any of the dangerous side effects in the list below, please seek immediate medical attention. Stop taking the medicine because these symptoms may be caused by an allergic reaction or they represent an unusual but severe reaction to the medicine. Once you’ve received medical attention, please let us know by sending us a message. 

  •       Severe headache
  •       Severe skin rash such as blistered and peeling skin
  •       Shortness of breath or wheezing
  •       Swelling in your face, lips, tongue, or throat 

CAUTION WITH PREEXISTING MEDICAL CONDITIONS  Please contact us if you have any of the following conditions so that we may properly assess your medical needs:

  • Glaucoma
  • Mania
  • Seizures
  • Suicidality
  • Cardiovascular Disease
  • Hyponatremia
  • Hypotension
  • Renal/Liver Disease
  • Or if you are Pregnant/Lactating

 

ALLERGIES  Send us a message and don’t take this medicine if you have any of the following allergies: Niacinamide, Cholecalciferol, Doxepin, Trazodone, Phenibut, Melatonin, Theanine, Magnesium, Potassium, Valerian Root, Ziziphus spinosa, Magnolia bark, Moringa, or gelatin.

MEDICATIONS THAT MAY INTERACT  Please discuss this medication with your doctors because, while rare, the following drug interactions may apply to you.  Send us a message and let us know if you’re taking any of the following medicines:

  • Statins
  • Nitrates
  • Antihypertensives (BBlockers, CCBlockers, ACE-I)
  • Cimetidine
  • Antidepressants (Citalopram, Escitalopram, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Lithium, Buspirone, MAO-Is)
  • Phenothiazine medicine (such as Chlorpromazine, Perphenazine, Promethazine, Prochlorperazine)
  • Antiarrhythmics (such as Digoxin, Flecainide, Quinidine)
  • Anticonvulsants: Phenytoin, Carbamazepine, Lamotrigine, Valproate, Barbiturate
  • Indinavir, Ritonavir, Efavirenz
  • Antifungal (Itraconazole, Ketoconazole)
  • NSAID (such as aspirin, celecoxib, diclofenac, ibuprofen, naproxen, diflunisal)
  • Migraine Medications
  • Warfarin
  • Potassium-sparing diuretics (Aldactone, Spironalactone)
  • Benzodiazepines: Clobazam, Diazepam, lorazepam
  • Fenofibrate, Gemfibrozil
  • Morphine, fentanyl, tramadol and opioid analgesics, loperamide
  • Propofol
  • Theophylline

Discontinuing The Medicine Common symptoms that can occur with abrupt discontinuation include nausea, vomiting, diarrhea, headaches, lightheadedness, sleep disturbances, and mood changes.

Improving Your Overall Health There are things that you must do to improve your health including eating healthier foods, stopping smoking if you smoke, reducing alcohol consumption, and exercising regularly. If you have health problems such as high blood pressure, cholesterol or diabetes, it’s also important to make sure they’re under good control. At a minimum, check your blood pressure once a year. It should be less than 140/90 and ideally under 120/80. Patients aged 40 or older should have a fasting blood sugar test to screen for diabetes.

Keep Your Doctor Informed It’s important to tell your doctor and pharmacist that you’ve started taking Sleep Synergy.  It can affect other medicines you’re taking. You can download the information about all your visits from the app or website for your own records and to share with your doctor.

ALTERNATIVE TREATMENT OPTIONS There are alternative treatments to the medicine we’ve prescribed, including other prescription medicines and psychotherapy.  We don’t prescribe controlled-substances, but it’s your right to see another doctor who may be able to provide you with these additional options.  You always have the option of declining our recommended treatment. There have been no head to head comparisons between prescription medicines, specifically controlled-substance alternatives, and psychotherapy (cognitive behavioral therapy – CBT).  We do not endorse or recommend any of these individual programs. Do not stop your prescription medicine without consulting your doctor.   

RISK OF MISDIAGNOSIS We rely on symptoms and your answers to our health questions to diagnose you with a sleep disorder.  It’s possible that we may diagnose and treat you for a sleep disorder even though you don’t have it, and that another condition is present that the medicine we prescribed won’t treat. It’s also possible that other potential physical causes of sleeplessness would be identified and investigated further if you were to see a doctor in person. As a result, you may end up taking this medicine unnecessarily and take on the risk of side effects from this medicine without any clear benefit.  We try to minimize this risk by using the latest medical guidelines and evidence to determine when it’s appropriate to treat you.  If you’re having serious side effects, you should see a doctor in person and keep us informed.

RISK THAT THE MEDICINE WON’T WORK Prescription medicines used to help with sleeplessness may not work effectively if there are other prescription medicines you’re taking, or you have medical conditions that interfere with their ability to be effective. It’s very important that you answer our health questions accurately because the questions we asked you helped us identify pertinent health conditions and the appropriate medicine.  If your symptoms aren’t improving with the medicine, or seem to be changing or worsening, you should stop taking the medicine we’ve prescribed and send us a message.  If you’re having serious side effects, you should see a doctor in person and keep us informed of your progress.

SLEEP OVERVIEW (mostly taken from Harvard sleep website)

Every night, nearly every person undergoes a remarkable change: we leave waking consciousness and for hours traverse a landscape of dreams and deep sleep. When we wake, we typically remember little or nothing about the hours that have just passed. Except in rare instances, we never contemplate and appreciate that we are sleeping while we are asleep. Thus, although everyone sleeps, most people would be hard-pressed to precisely define sleep. All organisms exhibit daily patterns of rest and activity that resemble the daily sleep and wakefulness patterns seen in humans. From observing changes in behavior and responsiveness, scientists have noted the following characteristics that accompany and in many ways define sleep: Sleep is a period of reduced activity, Sleep is associated with a typical posture, such as lying down with eyes closed in humans, Sleep results in a decreased responsiveness to external stimuli, Sleep is a state that is relatively easy to reverse (this distinguishes sleep from other states of reduced consciousness, such as hibernation and coma).  From observations of behavioral changes that accompany sleep and simultaneous physiological changes, scientists now define sleep in humans based on brain wave activity patterns and other physiological changes as described below.

Physiological Changes During Sleep  Many physiological variables are controlled during wakefulness at levels that are optimal for the body’s functioning. Our temperature, blood pressure, and levels of oxygen, carbon dioxide, and glucose in the blood remain quite constant during wakefulness. During sleep, however, physiological demands are reduced and temperature and blood pressure drop. In general, many of our physiological functions such as brain wave activity, breathing, and heart rate are quite variable when we are awake or during REM sleep, but are extremely regular when we are in non-REM sleep. 

Brain Activity For centuries, physicians believed that sleep was a period of brain inactivity, yet research over the last 60 years has shown us that the brain remains active during sleep. There is a progressive decrease in the activation or “firing” rate of most neurons throughout the brain as sleep progresses from wakefulness to non-REM sleep. Also, the patterns of neuron firing change from a seemingly random and variable activity pattern during wakefulness, to a much more coordinated and synchronous pattern during non-REM sleep.  During REM sleep (the stage of sleep most associated with dreaming) there is an increase in the firing rate of most neurons throughout the brain, as compared to non-REM sleep. In fact, the brain in REM sleep can even be more active than when we are awake. Patterns of brain activity during REM sleep are more random and variable, similar to during wakefulness. This pattern of brain activity during REM sleep probably underlies the intense dreaming that occurs during this state.  In all mammals and many other animals, sleep can be defined in much the same way that we define sleep for humans. However, there are some notable differences among species. When humans sleep, the entire brain is involved. Dolphins and whales, on the other hand, need to maintain consciousness while they sleep so they can occasionally surface to breathe. In these marine mammals, sleep occurs in only one hemisphere of their brain at a time—allowing for some degree of consciousness and vigilance to be maintained at all times. 

Body Temperature  Through a process known as thermoregulation, the temperature of our body is controlled by mechanisms such as shivering, sweating, and changing blood flow to the skin, so that body temperature fluctuates minimally around a set level during wakefulness. Just before we fall asleep, our bodies begin to lose some heat to the environment, which some researchers believe actually helps to induce sleep. During sleep, our central set temperature is reduced by 1 to 2°F. As a result, we use less energy maintaining our body temperature. It has been hypothesized that one of the primary functions of sleep is to conserve energy in this way.  Body temperature is still maintained, although at a slightly reduced level during non-REM sleep, but during REM sleep our body temperature falls to its lowest point. Curling up in bed under a blanket during the usual 10- to 30-minute periods of REM sleep ensures that we do not lose too much heat to the environment during this potentially dangerous time without thermoregulation.

Respiratory Changes Our breathing patterns also change during sleep. When we are awake, breathing is usually quite irregular, since it is affected by speech, emotions, exercise, posture, and other factors. As we progress from wakefulness through the stages of non-REM sleep, our breathing rate slightly decreases and becomes very regular. During REM sleep, the pattern becomes much more variable again, with an overall increase in breathing rate.

Cardiovascular Activity One of the possible functions of sleep is to give the heart a chance to rest from the constant demands of waking life. As compared to wakefulness, during non-REM sleep there is an overall reduction in heart rate and blood pressure. During REM sleep, however, there is a more pronounced variation in cardiovascular activity, with overall increases in blood pressure and heart rate. Additionally, changes in blood flow that causes erections to occur in males or swelling of the clitoris in females is characteristic of REM sleep The underlying reason for these considerable neural and physiological variations in REM sleep is currently unknown, and may be a by-product of REM-related changes in nervous system activity or related to dream content.

Increased Physiological Activity During Sleep For the most part, many physiological activities are reduced during sleep. For example, kidney function slows and the production of urine is decreased. However, some physiological processes may be maintained or even increased during sleep. For example, one of the greatest changes induced by sleep is an increase in the release of growth hormone.  Certain physiological activities associated with digestion, cell repair, and growth are often greatest during sleep, suggesting that cell repair and growth may be an important function of sleep.

Dreams  Dreaming occurs in both REM and NREM sleep.  One of the most notable but least understood characteristics of sleep is dreaming, during which our thoughts follow bizarre and seemingly illogical sequences, sometimes random and sometimes related to experiences gathered during wakefulness. Visually intense dreaming occurs primarily during REM sleep. However, not all dreams occur during REM sleep. For example, night terrors actually occur during non-REM sleep.  Varying explanations for dreaming, as well as the meanings of dreams, have been offered by philosophers and psychologists throughout history. Even with recent scientific investigations of dreaming, our dreams still remain something of a mystery. Some experts suggest that dreams represent the replay of the day’s events as a critical mechanism in the formation of memories, while others claim that the content of dreams is simply the result of random activity in the brain.

Waking up to Sleep  Our bodies require sleep in order to maintain proper function and health. In fact, we are programmed to sleep each night as a means of restoring our bodies and minds. Two interacting systems—the internal biological clock and the sleep-wake homeostat—largely determine the timing of our transitions from wakefulness to sleep and vice versa. These two factors also explain why, under normal conditions, we typically stay awake during the day and sleep at night. But what exactly happens when we drift off to sleep?  Prior to the era of modern sleep research in the early 1920s, scientists regarded sleep as an inactive brain state. It was generally accepted that as night fell and sensory inputs from the environment diminished, so too did brain function. In essence, scientists thought that the brain simply shut down during sleep, only to restart again when morning came.  EEGs are used in sleep studies to monitor brain activity during various stages of sleep.  In 1929, an invention that enabled scientists to record brain activity challenged this way of thinking. From recordings known as electroencephalograms (EEGs), researchers could see that sleep was a dynamic behavior, one in which the brain was highly active at times, and not turned off at all. Over time, sleep studies using EEGs and other instruments that measured eye movements and muscle activity would reveal two main types of sleep. These were defined by characteristic electrical patterns in a sleeping person’s brain, as well as the presence or absence of eye movements.  The two main types of sleep are rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. On an EEG, REM sleep, often called “active sleep,” is identifiable by its characteristic low-amplitude (small), high-frequency (fast) waves and alpha rhythm, as well as the eye movements for which it is named. Many sleep experts think that these eye movements are in some way related to dreams. Typically, when people are awakened from REM sleep, they report that they had been dreaming, often extremely vivid and sometimes bizarre dreams. In contrast, people report dreaming far less frequently when awakened from NREM sleep. Interestingly, during REM sleep muscles in the arms and legs are temporarily paralyzed. This is thought to be a neurological barrier that prevents us from “acting out” our dreams.  NREM sleep can be broken down into three distinct stages: N1, N2, and N3. In the progression from stage N1 to N3, brain waves become slower and more synchronized, and the eyes remain still. In stage N3, the deepest stage of NREM, EEGs reveal high-amplitude (large), low-frequency (slow) waves and spindles. This stage is referred to as “deep” or “slow-wave” sleep.

Cycling at Night  In healthy adults, sleep typically begins with NREM sleep. The pattern of clear rhythmic alpha activity associated with wakefulness gives way to N1, the first stage of sleep, which is defined by a low-voltage, mixed-frequency pattern. The transition from wakefulness to N1 occurs seconds to minutes after the start of the slow eye movements seen when a person first begins to nod off. This first period of N1 typically lasts just one to seven minutes. The second stage, or N2, which is signaled by sleep spindles and/or K complexes in the EEG recording, comes next and generally lasts 10 to 25 minutes. As N2 sleep progresses, there is a gradual appearance of the high-voltage, slow-wave activity characteristic of N3, the third stage of NREM sleep. This stage, which generally lasts 20 to 40 minutes, is referred to as “slow-wave,” “delta,” or “deep” sleep. As NREM sleep progresses, the brain becomes less responsive to external stimuli, and it becomes increasingly difficult to awaken an individual from sleep.  Following the N3 stage of sleep, a series of body movements usually signals an “ascent” to lighter NREM sleep stages. Typically, a 5- to 10-minute period of N2 precedes the initial REM sleep episode. REM sleep comprises about 20 to 25 percent of total sleep in typical healthy adults.  NREM sleep and REM sleep continue to alternate through the night in a cyclical fashion. Most slow-wave NREM sleep occurs in the first part of the night; REM sleep episodes, the first of which may last only one to five minutes, generally become longer through the night. During a typical night, N3 sleep occupies less time in the second cycle than the first and may disappear altogether from later cycles. The average length of the first NREM-REM sleep cycle is between 70 and 100 minutes; the average length of the second and later cycles is about 90 to 120 minutes. The reason for such a specific cycling pattern of NREM and REM sleep across the night is unknown. Some scientists speculate that specific sequences of NREM and REM sleep optimize both physical and mental recuperation as well as some aspects of memory consolidation that occur during sleep, but this has not been confirmed.  Sleep patterns can be affected by many factors, including age, the amount of recent sleep or wakefulness, the time of the day or night relative to an individual’s internal clock, other behaviors prior to sleep such as exercise, stress, environmental conditions such as temperature and light, and various chemicals.  For example, for the first year of life, sleep often begins in the REM state. The cyclical alternation of NREM-REM sleep in newborns is present from birth but at 50 to 60 minutes is much shorter than the 90-minute cycles that occur in adults. Consolidated nocturnal sleep and fully developed EEG patterns of NREM sleep stages emerge only after two to six months. Slow-wave sleep is greatest in young children and it decreases steadily with age, even if sleep duration does not change. This may be related to changes in the structure and function of the brain.  Sleep history—the quantity and quality of an individual’s sleep in recent days—can also have dramatic effects on sleep patterns. Repeatedly missing a night’s sleep, an irregular sleep schedule, or frequent disturbance of sleep can result in a redistribution of sleep stages, for instance, prolonged and deeper periods of slow-wave NREM sleep. Drugs may affect sleep stages as well. For example, alcohol before sleep tends to suppress REM sleep early in the night. As the alcohol is metabolized later in the night, REM sleep rebounds. However, awakenings also become more frequent during this time.

Sleeplessness  Most people don’t get enough sleep. We are a society that burns the candle at both ends, a nation where people stay up all night to study, work, or have fun. However, going without adequate sleep carries with it both short- and long-term consequences.  With one in five people sleeping less than six hours per night, and 75% having difficulty sleeping at least a few nights per week.  In the short term, a lack of adequate sleep can affect judgment, mood, ability to learn and retain information, and may increase the risk of serious accidents and injury, and also increases our risk for diabetes, obesity, and heart disease.  It also alters hormonal pathways that affect our appetite and metabolism, changes the expression of certain genes that affect our ability to respond appropriately in stressful situations, and even impacts our immune system, which governs processes that range from allergen sensitization, to fighting the common cold, and finding and eliminating cancerous cells.  A lack of sleep impacts our ability to concentrate, makes us more irritable, impatient, and increases our risk of developing a mood disorder, such as anxiety or depression.  In the long term, chronic sleep deprivation may lead to a host of health problems including obesity, diabetes, cardiovascular disease, and even early mortality.  

Obesity  Several studies have linked insufficient sleep and weight gain. For example, studies have shown that people who habitually sleep less than six hours per night are much more likely to have a higher than average body mass index (BMI) and that people who sleep eight hours have the lowest BMI. Sleep is now being seen as a potential risk factor for obesity along with the two most commonly identified risk factors: lack of exercise and overeating. Research into the mechanisms involved in regulating metabolism and appetite are beginning to explain what the connection between sleep and obesity might be.  During sleep, our bodies secrete hormones that help to control appetite, energy metabolism, and glucose processing. Obtaining too little sleep upsets the balance of these and other hormones. For example, poor sleep leads to an increase in the production of cortisol, often referred to as the “stress hormone.” Poor sleep is also associated with increases in the secretion of insulin following a meal. Insulin is a hormone that regulates glucose processing and promotes fat storage; higher levels of insulin are associated with weight gain, a risk factor for diabetes.  Insufficient sleep is also associated with lower levels of leptin, a hormone that alerts the brain that it has enough food, as well as higher levels of ghrelin, a biochemical that stimulates appetite. As a result, poor sleep may result in food cravings even after we have eaten an adequate number of calories. We may also be more likely to eat foods such as sweets that satisfy the craving for a quick energy boost. In addition, insufficient sleep may leave us too tired to burn off these extra calories with exercise.

Diabetes  Researchers have found that insufficient sleep may lead to type 2 diabetes by influencing the way the body processes glucose, the high-energy carbohydrate that cells use for fuel. One short-term sleep restriction study found that a group of healthy subjects who had their sleep cut back from 8 to 4 hours per night processed glucose more slowly than they did when they were permitted to sleep 12 hours. Numerous epidemiological studies also have revealed that adults who usually slept less than five hours per night have a greatly increased risk of having or developing diabetes.  In addition, researchers have correlated obstructive sleep apnea—a disorder in which breathing difficulties during sleep lead to frequent arousals—with the development of impaired glucose control similar to that which occurs in diabetes.

Heart Disease and Hypertension  Even minor periods of inadequate sleep can cause an elevation in blood pressure.  Studies have found that a single night of inadequate sleep in people who have existing hypertension can cause elevated blood pressure throughout the following day. This effect may begin to explain the correlation between poor sleep and cardiovascular disease and stroke. For example, one study found that sleeping too little (less than six hours) or too much (more than nine hours) increased the risk of coronary heart disease in women.  There is also growing evidence of a connection between obstructive sleep apnea and heart disease. People who have apnea typically experience multiple awakenings each night as a result of the closing of their airway when they fall asleep. In addition to these sleep disturbances, apnea sufferers also experience brief surges in blood pressure each time they wake up. Over time, this can lead to the chronic elevation of blood pressure known as hypertension, which is a major risk factor for cardiovascular disease. Fortunately, when sleep apnea is treated, blood pressure may go down. 

Mood Disorders  Given that a single sleepless night can cause people to be irritable and moody the following day, it is conceivable that chronic insufficient sleep may lead to long-term mood disorders. Chronic sleep issues have been correlated with depression, anxiety, and mental distress. In one study, subjects who slept four and a half hours per night reported feeling more stressed, sad, angry, and mentally exhausted. In another study, subjects who slept four hours per night showed declining levels of optimism and sociability as a function of days of inadequate sleep. All of these self-reported symptoms improved dramatically when subjects returned to a normal sleep schedule. 

Immune Function  It is natural for people to go to bed when they are sick. Substances produced by the immune system to help fight infection also cause fatigue. One theory proposes that the immune system evolved “sleepiness inducing factors” because inactivity and sleep provided an advantage: those who slept more when faced with an infection were better able to fight that infection than those who slept less. In fact, research in animals suggests that those animals who obtain more deep sleep following experimental challenge by microbial infection have a better chance of survival.

Alcohol  Despite its mild sedative qualities, alcohol often contributes to poor sleep.  Studies have shown that alcohol use is more prevalent among people who sleep poorly. The reason for this is twofold. First, alcohol acts as a mild sedative and is commonly used as a sleep aid among people who have sleep problems such as insomnia. Second, the sedative quality of alcohol is only temporary. As alcohol is processed by the body over a few hours it begins to stimulate the parts of the brain that cause arousal, in many cases causing awakenings and sleep problems later in the night.

How Sleep Deprivation Affects Mental Performance  Even when we are getting the amount of sleep we need, we can still expect normal fluctuations in our ability to function.  In addition to these normal fluctuations, not getting enough sleep—whether for just one night or over the course of weeks to months—has a significant effect on our ability to function. Sleep deprivation negatively impacts our mood, our ability to focus, and our ability to access higher-level cognitive functions. The combination of these factors is what we generally refer to as mental performance. In the laboratory, researchers use scientific studies to determine just how significantly varying levels of sleep disturbance impact various types of mental performance.  The most immediate effect of sleep deprivation is sleepiness. In our daily lives, we may experience this as a general fatigue, lack of motivation, or even the experience of nodding off. In the research or clinical setting, scientists measure sleepiness using a variety of methods. After a period of sleep deprivation, there are noticeable changes in brain activity, as measured by an electroencephalogram (EEG). These changes correspond to a lower level of alertness and a general propensity to sleep. Any period of continuous wakefulness beyond the typical 16 hours or so will generally lead to these measurable changes.  In addition to the feeling of sleepiness and changes in brain activity that accompany a night without sleep, other measures of performance are noticeably altered. Concentration, working memory, mathematical capacity, and logical reasoning are all aspects of cognitive function compromised by sleep deprivation. However, not all of these functions rely on the same regions of the brain, nor are they impacted by sleep deprivation to the same degree. As a result, people who are sleep deprived will begin to show deficits in many tasks that require logical reasoning or complex thought.  Determining just how much performance is affected by sleep loss is difficult, in part because of factors such as individual differences in sensitivity to sleep deprivation, as well as individual differences in motivation to stay alert despite sleep loss. Even so, the evidence is clear that a lack of sleep leads to poor performance.

Costly, Preventable Accidents  Insufficient sleep may not have led the news in reporting on serious accidents in recent decades. However, that doesn’t mean fatigue and inattention due to sleep loss didn’t play a role in these disasters. For example, investigators have ruled that sleep deprivation was a significant factor in the 1979 nuclear accident at Three Mile Island, as well as the 1986 nuclear meltdown at Chernobyl.  Investigations of the grounding of the Exxon Valdez oil tanker, as well as the explosion of the space shuttle Challenger, have concluded that sleep deprivation also played a critical role in these accidents. In both cases, those in charge of the operations and required to make critical decisions were operating under extreme sleep deprivation. While the Challenger disaster put the multi-billion dollar shuttle program in peril, the Exxon Valdez oil spill resulted in incalculable ecological, environmental, and economic damage.  In addition to the ties between such high-profile disasters and sleep deprivation, there is a growing recognition of the link between lack of sleep and medical errors in our hospitals. According to the Institutes of Medicine, over one million injuries and between 50,000 and 100,000 deaths each year result from preventable medical errors, and many of these may be the result of insufficient sleep, Doctors, especially newly graduated interns, are often expected to work continuous shifts of 24 to 36 hours with little or no opportunity for sleep.  Although it is difficult to estimate the extent that sleep deprivation plays in medical errors, studies have shown a significant impact. For example, a 2004 study led by Dr. Charles Czeisler of the Division of Sleep Medicine at Harvard Medical School found that hospitals could reduce the number of medical errors by as much as 36 percent by limiting an individual doctor’s work shifts to 16 hours and reducing the total work schedule to no more than 80 hours per week.  Long shifts and other factors that result in sleep loss have safety consequences for our highways as well. A National Sleep Foundation survey has revealed that 60 percent of adult drivers—about 168 million people—say they have driven a vehicle while feeling drowsy in the past year, and that more than one-third (103 million people) have actually fallen asleep at the wheel. Unfortunately, many of these situations end in tragedy. The National Highway Traffic Safety Administration estimates that 100,000 police-reported crashes are the direct result of driver fatigue each year, and they consider this a conservative estimate. More recent data suggests that the true number is likely much higher. The Institute of Medicine estimates—based on recent high quality naturalistic and epidemiologic studies—that drowsy driving is responsible for fully 20 percent of all motor vehicle crashes. That would mean that drowsy driving causes approximately 1 million crashes, 500,000 injuries, and 8,000 deaths each year in the U.S.

Sleep Hygiene  We spend roughly a third of our lives sleeping, a crucial time for tissue recovery and cellular repair via protein synthesis to heal damage caused by environmental stressors.  Experts agree that when people get the sleep they need, they will feel better and lead healthier, more productive lives.  Here are some simple recommendations to consider that may improve your sleep:

  • Create a routine for going to bed and waking up at the same time each day.
  • Check for underlying causes (change timing of med dose).
  • Block as much noise and light, especially electronic devices, as possible.
  • If you can’t fall asleep within 20 minutes, get out of bed rather than toss and turn for hours.
  • Nap if needed, but aim for midday; any later may interfere with sleep rhythm.
  • Exercise is stimulatory; finish aerobic exercises at least 3 hours before bedtime.
  • No caffeine-rich food/drink within 6 hours of bedtime (chocolate/soda/coffee/tea). 
  • Avoid nicotine and limit alcohol intake for at least 2 hours before bedtime.