6

Sleep Aids

The best way to get an idea of how many of us are not sleeping well is to look at the extent of use of medications to treat the problem. It is estimated that 10 to 25 percent of Americans use prescription sleep aids, spending about $4.5 billion each year on them. Prescriptions for them jumped from 47 million in 2006 to 60 million in 2012 and have continued to increase since then. Women, the elderly, and highly educated people use more of them. And over-the-counter (OTC) products for sleep are some of the most popular items in pharmacies. I advise you to be wary of all these medications and knowledgeable about any you may be taking.

Here is one cautionary tale—with a happy ending.

Marjorie, a self-proclaimed type A personality, was a single parent and busy real estate agent when she first experienced occasional sleeplessness in her late thirties. She found herself gradually increasing her coffee consumption to make it through long days but then needed an extra glass of wine to slow down and get to sleep at night.

When she was in her forties, Marjorie experienced significant changes in her life: her only child left for college, she lost her beloved dog, and she began to have symptoms of perimenopause. She now felt “twired”—simultaneously tired and wired—throughout the day. And she struggled almost nightly with insomnia.

Marjorie’s doctor believed that the insomnia resulted from a chemical imbalance common with aging and prescribed a low dose of zolpidem (Ambien), a popular sleeping pill. Her sleep improved at first, but Marjorie had to increase her dosage over time to maintain the drug’s effectiveness. She felt groggy throughout her mornings and began discovering signs that she had been unconsciously eating in the middle of the night. When Marjorie tried to give up medication, her insomnia actually worsened; she was now dependent on zolpidem.

Marjorie turned to an integrative sleep medicine practitioner for help. He determined that a complex set of lifestyle, medical, and psychological factors were at the root of her insomnia and that the medication was only perpetuating the problem. Together, they devised a plan to simultaneously wean her from zolpidem and restore her natural sleep. The practitioner recommended a temporary course of natural sleep aids—valerian and melatonin—to support this transition.

Cognitive behavioral therapy (CBT) was a key component of treatment, with a focus on how Marjorie’s thoughts, beliefs, and behaviors affected her sleep. It also addressed related lifestyle issues—her diet, exercise, and work and rest habits. She was advised to cut back her use of coffee during the day and wine at night and adhere to a regular sleep-wake schedule, with reduced light at night in her bedroom to make it more conducive to sleep.

Marjorie learned that like most people with insomnia she was hyperaroused—too stimulated by day to slow down and rest at night. She began a practice of mindfulness-based stress reduction (MBSR) to help manage this problem. She also began to see a counselor to deal with unresolved feelings of loss and loneliness, prompted by vivid dreams about her son and dog. Finally, after years of dreading the prospect of nightly struggles with insomnia, she started to sleep well again.

INSOMNIA

Insomnia refers to difficulty falling asleep, staying asleep, or obtaining restorative sleep. The National Sleep Foundation reports that 40 million Americans have a chronic sleep disorder and 62 percent of American adults experience a sleep problem a few nights a week.

Good sleep is a cornerstone of good mental and physical health. It restores energy and protects immunity. REM (rapid eye movement) sleep, the phase in which we dream, plays a critical role in learning, memory formation, and mood regulation. Poor sleep has been linked to chronic inflammation and increased risk for a broad range of illnesses, including depression, obesity, diabetes, cardiovascular disease, cancer, and autoimmune disorders.

The causes of insomnia are complex and intertwined with lifestyle. There are three types of factors—predisposing, precipitating, and perpetuating ones. Predisposing factors might include hyperarousal, the excessive use of substances like alcohol and caffeine, disruption of circadian rhythms (our twenty-four-hour cycle of physiological processes) through overexposure to light at night, and changes associated with aging. Precipitating factors refer to stressful events that push one over the threshold into insomnia. Examples include illness, divorce, menopause, and work or financial challenges. And perpetuating factors refer to misguided attempts at managing symptoms of insomnia, as by taking sleeping pills regularly. Medical conditions that cause pain or discomfort, or disrupt energy, as well as many commonly used medications, can also predispose us to, precipitate, or perpetuate insomnia.

PRESCRIPTION SLEEP AIDS: HOW THEY WORK, AND THEIR SIDE EFFECTS

Dozens of prescription drugs are marketed to treat insomnia. Benzodiazepines, a class of sedative anti-anxiety medications, are widely used at higher doses for insomnia. A number of other prescription sleep aids are known as Z-drugs, because the letter z appears in their generic names. Collectively, these medications are called sedative-hypnotics (from Hypnos, the Greek god of sleep). Although it’s not their primary function, sedating antidepressants, antipsychotics, and antihistamines are also used “off label” as sleep aids.

Consumer cost of these drugs ranges from less than $1 to more than $30 per dose. The pharmaceutical industry promotes their sale through extensive direct-to-consumer ads and through contributions that influence public sleep education. For example, the National Sleep Foundation, the leading nonprofit organization dedicated to improving sleep health, has received substantial funds from numerous pharmaceutical companies.

Few people who rely on the most popular sleep aids understand how they work, their effectiveness (or lack of it), and their potential side effects and adverse reactions.

Although the use of herbs and alcohol to promote sleep dates back thousands of years, the first pharmaceutical sleep aids weren’t developed until the nineteenth century. Barbiturates, a class of highly sedating and potentially dangerous drugs, came on the scene early in the twentieth century and dominated the sleeping pill market until the 1960s, when benzodiazepines (BDZs or “benzos”) were introduced as a safer alternative.

BDZs are sedating medications that reduce anxiety, relax muscles, and promote sleep. The many drugs in this class differ in how rapidly they take effect and how long they continue working. Their generic names all end in “-pam” or “-lam,” such as diazepam (Valium), alprazolam (Xanax), clonazepam (Klonopin), lorazepam (Ativan), triazolam (Halcion), and flurazepam (Dalmane). All work by boosting GABA (gamma-aminobutyric acid), a key neurotransmitter that calms brain activity. Since so much insomnia is associated with tension and anxiety, it’s not surprising that BDZs help promote sleep. Whether taken for anxiety or insomnia, they can be miraculously effective when first used. Consequently, they are among the most commonly prescribed drugs worldwide.

BDZs are usually recommended for short-term use of two to four weeks, but many people take them regularly. Combining them with alcohol or other sedating drugs or with opioids is dangerous and potentially lethal. Common side effects of BDZs include drowsiness, loss of balance, dizziness, confusion, amnesia, and breathing difficulties. Although BDZs can help us fall asleep faster and stay asleep longer, they disrupt sleep architecture—our normal cycles of sleep and dreams. More specifically, they increase light sleep at the expense of deep sleep, and they suppress dream sleep (REM). Long-term use frequently results in tolerance—the need to increase the dose to maintain the desired effect—and dependence. Dependence on BDZs is particularly stubborn; some addiction experts say it is harder to overcome than addiction to opioids.

Z-drugs, the first medications specifically formulated to treat insomnia (approved in the 1990s), are also among the most popular sleep aids around the world. Prescriptions for Z-drugs rose 350 percent between 1999 and 2010. Like BDZs, Z-drugs increase GABA activity, but they are more selective in the brain areas they target. They are purported to have fewer side effects than BDZs and to not damage sleep architecture.

The major Z-drugs—zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta)—share a basic chemical structure, but they vary in terms of effectiveness, duration of activity, speed of onset, and side effects. Use of these Z-drugs has been linked to parasomnias, bizarre unconscious nighttime behaviors that include sleepwalking, sleep driving, sleep telephoning, sleep cooking and eating, and sleep sex. Other side effects are drowsiness, amnesia, headache, dizziness, and depression. Z-drugs should not be combined with alcohol or other sedating medications.

First developed in the 1950s, sedating antidepressants (SADs), including amitriptyline (Elavil), doxepin (Silenor), mirtazapine (Remeron), and trazodone (Desyrel), are extensively used to treat insomnia, although the US Food and Drug Administration (FDA) has not approved them for that. SADs are types of antihistamines, all of which cause drowsiness as a well-known side effect. Typically prescribed at low doses for insomnia, SADs are purported to be safe for long-term use. Although it’s not entirely clear how it works, trazodone is one of the most popular sleep aids in use today and may be useful in treating insomnia caused by SSRI antidepressants (see chapter 9).

Sedating antidepressants have a potent anticholinergic effect, meaning they suppress the activity of acetylcholine, a key neurotransmitter. Many of their side effects are related to this activity: daytime sleepiness, weight gain, heart problems, digestive difficulties, headache, dry mouth, and blurred vision. SADs also aggravate restless leg syndrome and suppress REM sleep. These problems are of particular concern for the elderly, who generally use more anticholinergic drugs, such as allergy, antispasmodic, anti-nausea, and muscle relaxant medications. Overdosing on SADs is potentially lethal.

In addition to BDZs and SADs, other commonly used off-label sleep aids include antipsychotics, such as quetiapine (Seroquel) and olanzapine (Zyprexa); antiepileptics, such as gabapentin (Neurontin) and pregabalin (Lyrica); as well as an older antihistamine, hydroxyzine (Vistaril, Atarax). Although they share a common side effect of sedation, relatively little is known about their effectiveness and safety in the treatment of insomnia.

In recent years, ramelteon (Rozerem) and suvorexant (Belsomra), two new types of drugs that promote sleep in novel ways, have received FDA approval. Unlike other hypnotics, ramelteon promotes sleep by targeting brain receptors for melatonin, the neurotransmitter that regulates circadian rhythms. Designed to address sleep-onset difficulties, ramelteon is a relatively mild medication; nonetheless, side effects include daytime sleepiness, fatigue, concentration difficulties, headache, reduced libido, and fertility problems.

Suvorexant blocks the action of orexin (aka hypocretin), a neurotransmitter that promotes wakefulness. It was approved to treat insomnia in 2014 but not before the FDA considerably cut its proposed doses to reduce side effects. The most common of these are drowsiness, impaired driving, depression, suicidal thoughts, unusual dreams, hallucinations, and parasomnias similar to those seen with the Z-drugs. Suvorexant can also cause sleep paralysis, a frightening experience of being unable to move or speak for a few moments while falling asleep or awakening.

EFFECTIVENESS OF PRESCRIPTION SLEEP AIDS

Recent research using objective measures of sleep has raised serious questions about the overall effectiveness of sleep aids. On average, Z-drugs were found to reduce the time it takes to fall asleep by 13 minutes and add only 11 minutes to total sleep time. BDZs reduced sleep-onset time by 10 minutes and increased total sleep time by 32 minutes. And suvorexant decreased sleep-onset time by a mere 2.3 minutes, with an increase in total sleep time of 21 minutes. Although most of these improvements are statistically significant, they are functionally insignificant.

Also interesting is a discrepancy between these objective findings and subjective reports of satisfaction. Sleeping pill users estimated that their total sleep time increased by 52 minutes with BDZs and 32 minutes with Z-drugs. In all likelihood, the amnesia typically associated with these drugs interfered with remembering how badly they actually slept. Regular users of sleep aids also have more nighttime awakenings than insomniacs who do not use these products. When asked about this by a New York Times reporter, a representative of the pharmaceutical industry commented, “If you forget how long you lay in bed tossing and turning, in some ways that’s just as good as sleeping.”

OTC SLEEP AIDS

Each year, 10 to 20 percent of Americans take OTC sleep aids such as Zzzquil, Unisom, Nytol, Sominex, and various “PM drugs.” Their popularity may stem from a belief that OTC products are safer than prescription sleep aids. Certainly, they are easier to obtain and cheaper. They are also capable of causing undesirable side effects.

Most OTC sleep aids contain antihistamines like diphenhydramine (Benadryl). Some also contain acetaminophen or aspirin. Like SADs, OTC sleep aids promote sleep by suppressing histamine. Common side effects include extended drowsiness, disorientation, constipation, urinary retention, blurred vision, dry mouth, and reduced REM sleep.

THE PROBLEMS WITH SLEEP AIDS

Apart from the many side effects and adverse reactions of sleep aids, there are other problems associated with their long-term use. For example, the residual “hangover” common with most of them can leave users impaired even when feeling fully awake. This can significantly increase the risk of motor vehicle accidents and falls, especially among the elderly.

Long-term use of BDZs, Z-drugs, OTC sleep aids, and especially SADs results in tolerance—the need to increase dosage to maintain the same effect. Tolerance encourages overmedication, in the form of both excessive dosing and the use of risky combinations of drugs and substances. History is replete with stories of celebrities who lost their lives to overmedication in a desperate pursuit of sleep. And, sadly, there are many more untold stories of ordinary people who did the same.

Although sleep aids purportedly treat insomnia, they are actually symptom suppressive—that is, they mask sleeplessness while failing to address its underlying causes. Consequently, discontinuation of these drugs often results in rebound insomnia, a recurrence and even worsening of one’s original symptoms. Rebound insomnia can last from days to months, perpetuating dependence and addiction.

While the risk of tolerance, dependence, and rebound insomnia is ostensibly lower with Z-drugs than with BDZs, in reality, the two are similar in terms of these adverse reactions. One significant disadvantage of BDZs is their potential for true addiction, with an extremely challenging withdrawal process. (See chapter 9 for the story of one woman’s struggle with this.)

Never stop a sleep medication abruptly. It is much safer to taper the dose down gradually and under medical supervision. Depending on the type of drug, the dosage, and the length of use, sleep aid withdrawal can range from a minor bump in the road to a protracted ordeal lasting weeks or months. The withdrawal process is marked by symptoms that wax and wane, including rebound insomnia, anxiety, depression, and cognitive challenges.

While the long-term effects of Z-drugs on REM sleep are unclear, BDZs, SADs, and OTC sleep aids are known to suppress dreaming. These drugs have been linked to depression, dementia, and Alzheimer’s disease, conditions also associated with impaired REM sleep.

More than a dozen studies have raised concerns about links between sleep aid use, cancer, and death rates. One study of more than ten thousand people who took Z-drugs or BDZs found a 35 percent increase in cancer rates as well as a correlation between increased use and death rates. Even people taking fewer than eighteen pills per year had increased mortality.

INTEGRATIVE MEDICINE APPROACHES TO MANAGING INSOMNIA

Despite widely publicized concerns about their safety and efficacy, sleep aids remain the most popular treatment for insomnia. This is reinforced by the medicalization of sleep—an industry-concocted notion that insomnia is caused by a chemical imbalance in the brain that can be remedied with a quick pharmaceutical fix. This perspective depersonalizes sleep. It discourages addressing critical personal and lifestyle issues and undermines our sleep self-efficacy—trust in our ability to heal our own sleep.

Like the common cold, occasional sleeplessness is transient and usually resolves on its own. But like a cold that persists, chronic insomnia should be treated professionally.

Because primary care practitioners generally do not have the training or the time to effectively address insomnia, they are more likely to prescribe sleep aids or refer patients for unnecessary overnight sleep studies. In contrast, behavioral sleep medicine (BSM) specialists are trained to address insomnia with personalized cognitive behavioral therapy for insomnia (CBT-I). A number of websites offer CBT-I programs that can be coupled with integrative medicine consultations.

Integrative medicine encourages a comprehensive approach to insomnia rather than a purely chemical one. It relies on the principle of endogenous healing—a belief in our innate capacity and natural inclination to sleep. Instead of forcing people back to sleep with a drug, integrative medicine advocates the gentler approach of invoking sleep—with the active participation of the patient. Let’s take a look at some of the methods used.

Noise Reduction

Most insomnia is not caused by insufficient sleepiness but by overstimulation arising from biomedical, psychological, and environmental factors or “body, mind, and bed noise.” Noise reduction is about identifying and managing the kinds of excessive stimulation that interfere with our innate tendency to sleep.

Body noise refers to a wide range of biomedical problems that can contribute to sleeplessness. Examples include the adverse effects of caffeine or alcohol, pain or discomfort, digestive problems such as GERD, airborne and food allergies, symptoms of perimenopause, restless leg syndrome, and the side effects of medications. A lack of adequate physical activity as well as chronic muscle tension, which is usually rooted in anxiety, are also examples of body noise.

Conscientiously managing diet, substance use, and medical symptoms will help reduce body noise. It is also essential to evaluate the possible side effects on sleep of all medications you are using and consider alternatives as needed. Various mind-body techniques are available to help alleviate muscle tension: yoga, progressive muscular relaxation, breath work, self-hypnosis, transcranial stimulation, and neurofeedback. Mindfulness-based stress reduction (MBSR) is a structured form of meditation that has been shown to be very useful in improving sleep, as well as making it easier to taper off sleep aids.

Mind noise refers to sleep-impeding thoughts and feelings rooted in misguided beliefs. It is most effectively addressed with CBT-I, a set of techniques that help modify thoughts, beliefs, and behaviors that interfere with sleep. Although it does not work as quickly as sleep aids, CBT-I is significantly more effective and enduring. It commonly includes stimulus control and sleep restriction—two strategies that reduce insomnia by selectively limiting time in bed. CBT-I is particularly useful to mitigate excessive sleep effort, the common tendency of trying too hard to make sleep happen, which invariably backfires.

Integrative medicine also acknowledges the psycho-spiritual dimension of sleep. If there is a secret to falling asleep, it is the recognition that the awake part of us, by definition, simply cannot make it happen. In one sense, we never need to “go to sleep” because sleep already resides within each of us. We need, instead, to practice letting go of wakefulness. Mastering relaxation techniques, such as breath control, can help greatly. Limiting use of computers, cell phones, and other forms of intrusive technology may be critically important.

Bed noise refers to such environmental factors as literal noise, excessive background light, poor air quality, and too-warm ambient temperature (above 68°F/20°C). A sleep-conducive bedroom should also feel safe—both physically and psychologically.

Herbal Remedies and Other Natural Products

Some botanical medicines and nutraceutical sleep supplements can help reduce insomnia as well as assist in withdrawal from sleep aids. In general, these products are both safer and less expensive than conventional sleep aids. They are best used as part of a comprehensive noise-reduction program. Although there is extensive information about natural sleep products on the Internet, I recommend seeking professional guidance—from a knowledgeable pharmacist or physician—about using them. Three of the most popular are valerian, L-theanine, and melatonin, all of which are well researched.

Valerian is a potent sedating herb that can support normal sleep architecture as well as deep and REM sleep. Used in many parts of the Western world for centuries, valerian has a good safety profile, but it should not be combined with other sedating substances or medications. It is best taken in the form of a standardized extract in capsules, 400 to 600 milligrams, a half hour before bedtime.

L-theanine is an amino acid with a good safety profile that effectively reduces anxiety and promotes relaxation. Extracted from tea, it increases alpha EEG (relaxed brain waves) and increases GABA levels. Because anxiety is a common factor in sleeplessness, L-theanine can be helpful in treating insomnia. It can also counter some of the stimulating effects of caffeine. The usual dose is 200 to 250 milligrams.

Melatonin is a neurotransmitter that plays a key and complex role in our nighttime physiology by regulating circadian rhythms and supporting healthy sleep and dreams. Available in a wide range of doses as well as regular and time-release formulations, it can help address various sleep concerns when used appropriately. Unfortunately, melatonin is often misunderstood and misused. Despite its good safety record, taking high doses will not necessarily help with, and might actually impede, sleep. Many dosage forms are available. I recommend 2.5 milligrams as a sublingual (under-the-tongue) tablet at bedtime.

BOTTOM LINE

Insomnia is a glaring symptom of an unhealthy lifestyle. Sleep aids suppress this symptom and replace it with counterfeit sleep that does not provide natural repose. Given their limited effectiveness, side effects, and serious adverse reactions, over-prescription and overuse of sleep aids are not justifiable. If they are to be taken at all, sleep aids are best used for short-term management of sleep problems, such as those related to emotional trauma (for example, a death in the family) or travel between different time zones. Safe and effective interventions that address insomnia as a lifestyle issue should always take precedence.