فصل 14

CHAPTER 14

Hurting and Helping Your Sleep

Pills vs. Therapy

In the past month, almost 10 million people in America will have swallowed some kind of a sleeping aid. Most relevant, and a key focus of this chapter, is the (ab)use of prescription sleeping pills. Sleeping pills do not provide natural sleep, can damage health, and increase the risk of life-threatening diseases. We will explore the alternatives that exist for improving sleep and combating insipid insomnia.

SHOULD YOU TAKE TWO OF THESE BEFORE BED?

No past or current sleeping medications on the legal (or illegal) market induce natural sleep. Don’t get me wrong—no one would claim that you are awake after taking prescription sleeping pills. But to suggest that you are experiencing natural sleep would be an equally false assertion.

The older sleep medications—termed “sedative hypnotics,” such as diazepam—were blunt instruments. They sedated you rather than assisting you into sleep. Understandably, many people mistake the former for the latter. Most of the newer sleeping pills on the market present a similar situation, though they are slightly less heavy in their sedating effects. Sleeping pills, old and new, target the same system in the brain that alcohol does—the receptors that stop your brain cells from firing—and are thus part of the same general class of drugs: sedatives. Sleeping pills effectively knock out the higher regions of your brain’s cortex.

If you compare natural, deep-sleep brainwave activity to that induced by modern-day sleeping pills, such as zolpidem (brand name Ambien) or eszopiclone (brand name Lunesta), the electrical signature, or quality, is deficient. The electrical type of “sleep” these drugs produce is lacking in the largest, deepest brainwaves.I Adding to this state of affairs are a number of unwanted side effects, including next-day grogginess, daytime forgetfulness, performing actions at night of which you are not conscious (or at least have partial amnesia of in the morning), and slowed reaction times during the day that can impact motor skills, such as driving.

True even of the newer, shorter-acting sleeping pills on the market, these symptoms instigate a vicious cycle. The waking grogginess can lead people to reach for more cups of coffee or tea to rev themselves up with caffeine throughout the day and evening. That caffeine, in turn, makes it harder for the individual to fall asleep at night, worsening the insomnia. In response, people often take an extra half or whole sleeping pill at night to combat the caffeine, but this only amplifies the next-day grogginess from the drug hangover. Even greater caffeine consumption then occurs, perpetuating the downward spiral.

Another deeply unpleasant feature of sleeping pills is rebound insomnia. When individuals stop taking these medications, they frequently suffer far worse sleep, sometimes even worse than the poor sleep that led them to seek out sleeping pills to begin with. The cause of rebound insomnia is a type of dependency in which the brain alters its balance of receptors as a reaction to the increased drug dose, trying to become somewhat less sensitive as a way of countering the foreign chemical within the brain. This is also known as drug tolerance. But when the drug is stopped, there is a withdrawal process, part of which involves an unpleasant spike in insomnia severity.

We should not be surprised by this. The majority of prescription sleeping pills are, after all, in a class of physically addictive drugs. Dependency scales with continued use, and withdrawal ensues in abstinence. Of course, when patients come off the drug for a night and have miserable sleep as a result of rebound insomnia, they often go right back to taking the drug the following night. Few people realize that this night of severe insomnia, and the need to start retaking the drug, is partially or wholly caused by the persistent use of sleeping pills to begin with.

The irony is that many individuals experience only a slight increase in “sleep” from these medications, and the benefit is more subjective than objective. A recent team of leading medical doctors and researchers examined all published studies to date on newer forms of sedative sleeping pills that most people take.II They considered sixty-five separate drug-placebo studies, encompassing almost 4,500 individuals. Overall, participants subjectively felt they fell asleep faster and slept more soundly with fewer awakenings, relative to the placebo. But that’s not what the actual sleep recordings showed. There was no difference in how soundly the individuals slept. Both the placebo and the sleeping pills reduced the time it took people to fall asleep (between ten and thirty minutes), but the change was not statistically different between the two. In other words, there was no objective benefit of these sleeping pills beyond that which a placebo offered.

Summarizing the findings, the committee stated that sleeping pills only produced “slight improvements in subjective and polysomnographic sleep latency”—that is, the time it takes to fall asleep. The committee concluded the report by stating that the effect of current sleeping medications was “rather small and of questionable clinical importance.” Even the newest sleeping pill for insomnia, called suvorexant (brand name Belsomra), has proved minimally effective, as we discussed in chapter 12. Future versions of such drugs may offer meaningful sleep improvements, but for now the scientific data on prescription sleeping pills suggests that they may not be the answer to returning sound sleep to those struggling to generate it on their own.

SLEEPING PILLS—THE BAD, THE BAD, AND THE UGLY

Existing prescription sleeping pills are minimally helpful, but are they harmful, even deadly? Numerous studies have something to say on this point, yet much of the public remains unaware of their findings.

Natural deep sleep, as we have previously learned, helps cement new memory traces within the brain, part of which require the active strengthening of connections between synapses that make up a memory circuit. How this essential nighttime storage function is affected by drug-induced sleep has been the focus of recent animal studies. After a period of intense learning, researchers at the University of Pennsylvania gave animals a weight-appropriate dose of Ambien or a placebo and then examined the change in brain rewiring after sleep in both groups. As expected, natural sleep solidified memory connections within the brain in the placebo condition that had been formed during the initial learning phase. Ambien-induced sleep, however, not only failed to match these benefits (despite the animals sleeping just as long), but caused a 50 percent weakening (unwiring) of the brain-cell connections originally formed during learning. In doing so, Ambien-laced sleep became a memory eraser, rather than engraver.

Should similar findings continue to emerge, including in humans, pharmaceutical companies may have to acknowledge that, although users of sleeping pills may fall asleep nominally faster at night, they should expect to wake up with few(er) memories of yesterday. This is of special concern considering the average age for those receiving sleep medication prescriptions is decreasing, as sleep complaints and incidents of pediatric insomnia increase. Should the former be true, doctors and parents may need to be vigilant about giving in to the temptation of prescriptions. Otherwise, young brains, which are still being wired up into the early twenties, will be attempting the already challenging task of neural development and learning under the subverting influence of prescription sleeping pills.III

Even more concerning than brain rewiring are medical effects throughout the body that come with the use of sleeping pills—effects that aren’t widely known but should be. Most controversial and alarming are those highlighted by Dr. Daniel Kripke, a physician at the University of California, San Diego. Kripke discovered that individuals using prescription sleep medications are significantly more likely to die and to develop cancer than those who do not.IV I should note at the outset that Kripke (like me) has no vested interest in any particular drug company, and therefore does not stand to financially gain or lose on the basis of a particular examination of health relationships that exist with sleeping pills—good or bad.

In the early 2000s, insomnia rates ballooned and sleeping pill prescriptions escalated dramatically. It also meant much more data was available. Kripke began examining these large epidemiological databases. He wanted to explore whether there was a relationship between sleeping pill use and altered disease or mortality risk. There was. Time and again, the same message emerged from the analyses: individuals taking sleeping pills were significantly more likely to die across the study periods (usually a handful of years) than those who were not, the reasons for which we will soon discuss.

Often, however, it was tricky to conduct a well-matched comparison with these early databases, as there were not enough participants or measured factors that he could control for to really tease out a pure sleeping pill effect. By 2012, however, there were. Kripke and his colleagues set up a well-controlled comparison, examining more than 10,000 patients taking sleeping pills, the vast majority of whom were taking zolpidem (brand name Ambien), though some were taking temazepam (brand name Restoril). He contrasted them with 20,000 very well matched individuals of similar age, race, gender, and background, but who were not taking sleeping pills. In addition, Kripke was able to control for many other factors that could inadvertently contribute to mortality, such as body mass index, history of exercise, smoking, and drinking. He looked at the likelihood of disease and death across a two-and-a-half-year window, shown in Figure 15.V,VI

Those taking sleeping pills were 4.6 times more likely to die over this short two-and-a-half-year period than those who were not using sleeping pills. Kripke further discovered that the risk of death scaled with the frequency of use. Those individuals classified as heavy users, defined as taking more than 132 pills per year, were 5.3 times more likely to die over the study period than matched control participants who were not using sleeping pills.

Figure 15: Risk of Death from Sleeping Pills

More alarming was the mortality risk for people who only dabbled in sleeping pill use. Even very occasional users—those defined as taking just eighteen pills per year—were still 3.6 times more likely to die at some point across the assessment window than non-users. Kripke isn’t the only researcher finding such mortality risk associations. There are now more than fifteen such studies from different groups around the world showing higher rates of mortality in those who use sleeping pills.

What was killing those individuals using sleeping pills? That question is harder to answer from the available data, though it is clear that the sources are many. In an attempt to find answers, Kripke and other independent research groups have now evaluated data from studies involving almost all of the common sleeping pills, including zolpidem (Ambien), temazepam (Restoril), eszopiclone (Lunesta), zaleplon (Sonata), and other sedating drugs, such as triazolam (Halcion) and flurazepam (Dalmane).

One frequent cause of mortality appears to be higher-than-normal rates of infection. Also discussed in earlier chapters, natural sleep is one of the most powerful boosters of the immune system, helping ward off infection. Why, then, do individuals who are taking sleeping pills that purportedly “improve” sleep suffer higher rates of various infections, when the opposite is predicted? It is possible that medication-induced sleep does not provide the same restorative immune benefits as natural sleep. This would be most troubling for the elderly. Older adults are far more likely to suffer from infections. Alongside newborns, they are the most immunologically vulnerable individuals in our society. Older adults are also the heaviest users of sleeping pills, representing more than 50 percent of the individuals prescribed such drugs. Based on these coincidental facts, it may be time for medicine to reappraise the prescription frequency of sleeping pills in the elderly.

Another cause of death linked to sleeping pill use is an increased risk for fatal car accidents. This is most likely caused by the non-restorative sleep such drugs induce and/or the groggy hangover that some suffer, both of which may leave individuals drowsy while driving the next day. Higher risk for falls at night was a further mortality factor, particularly in the elderly. Additional adverse associations in users of prescription sleeping pills included higher rates of heart disease and stroke.

Then broke the story of cancer. Earlier studies had hinted at a relationship between the sleep medications and mortality risk from cancer, but were not as well controlled in terms of comparisons. Kripke’s study did a far better job in this regard, and included the newer, more relevant sleeping medication Ambien. Individuals taking sleeping pills were 30 to 40 percent more likely to develop cancer within the two-and-a-half-year period of the study than those who were not. The older sleeping medications, such as temazepam (Restoril), had a stronger association, with those on mild to moderate doses suffering more than a 60 percent increased cancer risk. Those taking the highest dose of zolpidem (Ambien) were still vulnerable, suffering almost a 30 percent greater likelihood of developing cancer across the two-and-a-half-year study duration.

Interestingly, animal experiments conducted by the drug companies themselves hint at the same carcinogenic danger. While the data from the drug companies submitted to the FDA website is somewhat obscure, it seems higher rates of cancer may have emerged in rats and mice dosed with these common sleeping pills.

Do these findings prove that sleeping pills cause cancer? No. At least not by themselves. There are also alternative explanations. For example, it could be that the poor sleep that individuals were suffering prior to taking these drugs—that which motivated the prescription to begin with—and not the sleeping pills themselves, predisposed them to ill health. Moreover, the more problematic an individual’s prior sleep, perhaps the more sleeping pills they later consumed, thus accounting for the dose-dependent mortality and dose-carcinogen relationships Kripke and others observed.

But it is equally possible that sleeping pills do cause death and cancer. To obtain a definitive answer we would need a dedicated clinical trial expressly designed to examine these particular morbidity and mortality risks. Ironically, such a trial may never be conducted, since a board of ethics may deem the already apparent death hazard and carcinogenic risks associated with sleeping pills to be too high.

Shouldn’t drug companies be more transparent about the current evidence and risks surrounding sleeping pill use? Unfortunately, Big Pharma can be notoriously unbending within the arena of revised medical indications. This is especially true once a drug has been approved following basic safety assessments, and even more so when profit margins become exorbitant. Consider that the original Star Wars movies—some of the highest-grossing films of all time—required more than forty years to amass $3 billion in revenue. It took Ambien just twenty-four months to amass $4 billion in sales profit, discounting the black market. That’s a large number, and one I can only imagine influences Big Pharma decision-making at all levels.

Perhaps the most conservative and least litigious conclusion one can make about all of this evidence is that no study to date has shown that sleeping pills save lives. And after all, isn’t that the goal of medicine and drug treatments? In my scientific, though non-medical, opinion, I believe that the existing evidence warrants far more transparent medical education of any patient who is considering taking a sleeping pill, at the very least. This way, individuals can appreciate the risks and make informed choices. Do you, for example, feel differently about using or continuing to use sleeping pills having learned about this evidence?

To be very clear, I am not anti-medication. On the contrary, I desperately want there to be a drug that helps people obtain truly naturalistic sleep. Many of the drug company scientists who create sleeping medicines do so with nothing but good intent and an honest desire to help those for whom sleep is problematic. I know, because I have met many of them in my career. And as a researcher, I am keen to help science explore new medications in carefully controlled, independent studies. If such a drug—one with sound scientific data demonstrating benefits that far outweigh any health risks—is ultimately developed, I would support it. It is simply that no such medication currently exists.

DON’T TAKE TWO OF THESE, INSTEAD TRY THESE

While the search for more sophisticated sleep drugs continues, a new wave of exciting, non-pharmacological methods for improving sleep are fast emerging. Beyond the electrical, magnetic, and auditory stimulation methods for boosting deep-sleep quality that I have previously discussed (and that are still in embryonic stages of development) there are already numerous and effective behavioral methods for improving your sleep, especially if you are suffering from insomnia.

Currently, the most effective of these is called cognitive behavioral therapy for insomnia, or CBT-I, and it is rapidly being embraced by the medical community as the first-line treatment. Working with a therapist for several weeks, patients are provided with a bespoke set of techniques intended to break bad sleep habits and address anxieties that have been inhibiting sleep. CBT-I builds on basic sleep hygiene principles that I describe in the appendix, supplemented with methods individualized for the patient, their problems, and their lifestyle. Some are obvious, others not so obvious, and still others are counterintuitive.

The obvious methods involve reducing caffeine and alcohol intake, removing screen technology from the bedroom, and having a cool bedroom. In addition, patients must (1) establish a regular bedtime and wake-up time, even on weekends, (2) go to bed only when sleepy and avoid sleeping on the couch early/mid-evenings, (3) never lie awake in bed for a significant time period; rather, get out of bed and do something quiet and relaxing until the urge to sleep returns, (4) avoid daytime napping if you are having difficulty sleeping at night, (5) reduce anxiety-provoking thoughts and worries by learning to mentally decelerate before bed, and (6) remove visible clockfaces from view in the bedroom, preventing clock-watching anxiety at night.

One of the more paradoxical CBT-I methods used to help insomniacs sleep is to restrict their time spent in bed, perhaps even to just six hours of sleep or less to begin with. By keeping patients awake for longer, we build up a strong sleep pressure—a greater abundance of adenosine. Under this heavier weight of sleep pressure, patients fall asleep faster, and achieve a more stable, solid form of sleep across the night. In this way, a patient can regain their psychological confidence in being able to self-generate and sustain healthy, rapid, and sound sleep, night after night: something that has eluded them for months if not years. Upon reestablishing a patient’s confidence in this regard, time in bed is gradually increased.

While this may all sound a little contrived or even dubious, skeptical readers, or those normally inclined toward drugs for help, should first evaluate the proven benefits of CBT-I before dismissing it outright. Results, which have now been replicated in numerous clinical studies around the globe, demonstrate that CBT-I is more effective than sleeping pills in addressing numerous problematic aspects of sleep for insomnia sufferers. CBT-I consistently helps people fall asleep faster at night, sleep longer, and obtain superior sleep quality by significantly decreasing the amount of time spent awake at night.VII More importantly, the benefits of CBT-I persist long term, even after patients stop working with their sleep therapist. This sustainability stands in stark contrast to the punch of rebound insomnia than individuals experience following the cessation of sleeping pills.

So powerful is the evidence favoring CBT-I over sleeping pills for improved sleep across all levels, and so limited or nonexistent are the safety risks associated with CBT-I (unlike sleeping pills), that in 2016, the American College of Physicians made a landmark recommendation. A committee of distinguished sleep doctors and scientists evaluated all aspects of the efficacy and safety of CBT-I relative to standard sleeping pills. Published in the prestigious journal Annals of Internal Medicine, the conclusion from this comprehensive evaluation of all existing data was this: CBT-I must be used as the first-line treatment for all individuals with chronic insomnia, not sleeping pills.VIII

You can find more resources on CBT-I, and a list of qualified therapists, from the National Sleep Foundation’s website.IX If you have, or think you have, insomnia, please make use of these resources before turning to sleeping pills.

GENERAL GOOD SLEEP PRACTICES

For those of us who are not suffering from insomnia or another sleep disorder, there is much we can do to secure a far better night of sleep using what we call good “sleep hygiene” practices, for which a list of twelve key tips can be found at the National Institutes of Health website; also offered in the appendix of this book.X All twelve suggestions are superb advice, but if you can only adhere to one of these each and every day, make it: going to bed and waking up at the same time of day no matter what. It is perhaps the single most effective way of helping improve your sleep, even though it involves the use of an alarm clock.

Last but not least, two of the most frequent questions I receive from members of the public regarding sleep betterment concern exercise and diet.

Sleep and physical exertion have a bidirectional relationship. Many of us know of the deep, sound sleep we often experience after sustained physical activity, such as a daylong hike, an extended bike ride, or even an exhausting day of working in the garden. Scientific studies dating back to the 1970s support some of this subjective wisdom, though perhaps not as strongly as you’d hope. One such early study, published in 1975, shows that progressively increased levels of physical activity in healthy males results in a corresponding progressive increase in the amount of deep NREM sleep they obtain on subsequent nights. In another study, however, active runners were compared with age- and gender-matched non-runners. While runners had somewhat higher amounts of deep NREM sleep, it was not significantly different to the non-runners.

Larger and more carefully controlled studies offer somewhat more positive news, but with an interesting wrinkle. In younger, healthy adults, exercise frequently increases total sleep time, especially deep NREM sleep. It also deepens the quality of sleep, resulting in more powerful electrical brainwave activity. Similar, if not larger, improvements in sleep time and efficiency are to be found in midlife and older adults, including those who are self-reported poor sleepers or those with clinically diagnosed insomnia.

Typically, these studies involve measuring several nights of initial baseline sleep in individuals, after which they are placed on a regimen of exercise across several months. Researchers then examine whether or not there are corresponding improvements in sleep as a consequence. On average, there are. Subjective sleep quality improves, as does total amount of sleep. Moreover, the time it takes participants to fall asleep is usually less, and they report waking up fewer times across the night. In one of the longest manipulation studies to date, older adult insomniacs were sleeping almost one hour more each night, on average, by the end of a four-month period of increased physical activity.

Unexpected, however, was the lack of a tight relationship between exercise and subsequent sleep from one day to the next. That is, subjects did not consistently sleep better at night on the days they exercised compared with the days when they were not required to exercise, as one would expect. Less surprising, perhaps, is the inverse relationship between sleep and next-day exercise (rather than the influence of exercise on subsequent sleep at night). When sleep was poor the night prior, exercise intensity and duration were far worse the following day. When sleep was sound, levels of physical exertion were powerfully maximal the next day. In other words, sleep may have more of an influence on exercise than exercise has on sleep.

It is still a clear bidirectional relationship, however, with a significant trend toward increasingly better sleep with increasing levels of physical activity, and a strong influence of sleep on daytime physical activity. Participants also feel more alert and energetic as a result of the sleep improvement, and signs of depression proportionally decrease. It is clear that a sedentary life is one that does not help with sound sleep, and all of us should try to engage in some degree of regular exercise to help maintain not only the fitness of our bodies but also the quantity and quality of our sleep. Sleep, in return, will boost your fitness and energy, setting in motion a positive, self-sustaining cycle of improved physical activity (and mental health).

One brief note of caution regarding physical activity: try not to exercise right before bed. Body temperature can remain high for an hour or two after physical exertion. Should this occur too close to bedtime, it can be difficult to drop your core temperature sufficiently to initiate sleep due to the exercise-driven increase in metabolic rate. Best to get your workout in at least two to three hours before turning the bedside light out (none LED-powered, I trust).

When it comes to diet, there is limited research investigating how the foods you eat, and the pattern of eating, impact your sleep at night. Severe caloric restriction, such as reducing food intake to just 800 calories a day for one month, makes it harder to fall asleep normally, and decreases the amount of deep NREM sleep at night.

What you eat also appears to have some impact on your nighttime sleep. Eating a high-carbohydrate, low-fat diet for two days decreases the amount of deep NREM sleep at night, but increases the amount of REM sleep dreaming, relative to a two-day diet low in carbohydrates and high in fat. In a carefully controlled study of healthy adult individuals, a four-day diet high in sugar and other carbohydrates, but low in fiber, resulted in less deep NREM sleep and more awakenings at night.XI

It is hard to make definitive recommendations for the average adult, especially because larger-scale epidemiological studies have not shown consistent associations between eating specific food groups and sleep quantity or quality. Nevertheless, for healthy sleep, the scientific evidence suggests that you should avoid going to bed too full or too hungry, and shy away from diets that are excessively biased toward carbohydrates (greater than 70 percent of all energy intake), especially sugar.