Sleeping Pills For Use in Insomnia: What Are the Risks?

By Dr. Steven Scharf

Hypnotics (sleeping pills) are relatively commonly prescribed. While exact numbers are difficult to come by, it has been estimated that 40 million or more Americans regularly use sleeping pills. Is there a risk from the regular use of sleeping pills? For reference, at the end of this article, there is a list of the various commonly used types of sleeping pills.

Recently, the British Medical Journal (reference: Kripke DF, et al, BMJ Open 2012;2: e000850) published the results of a large scale study in patients belonging to a large Health Maintenance Organization (HMO). Since all the records of this HMO have been electronic since at least 2002, thus affording the opportunity to survey a large number of patients and their outcomes. The authors identified 12,465 patients with at least one order for a hypnotic medication. The authors then matched these by sex, age, smoking status, and observation period to 24,793 patients who never received an order for a hypnotic. After statistically adjusting for age, sex, smoking, body mass, ethnicity, marital status, alcohol use and prior cancer, the authors found that the death rate among those using hypnotics was over 4-fold greater than those not using hypnotics. The range of hypnotics was reasonably representative of what is available by prescription. Because the findings were so dramatic, several news stations picked up this study for coverage.

Indeed, the first author of this well-done study has become a crusader of sorts against the use of hypnotics and, along with others, believes that sleeping pills pose a risk for excess mortality. To address some of the concerns that have been raised in the public conscience regarding the use of sleep pills, this article addresses this issue head-on and honestly describe what is known about the risks, and what is not known.

Did This Study Show That Sleeping Pills Cause Death?

This study is called a retrospective, which is study looking backward. In retrospective studies, conditions are often not able to be well controlled, so they may not be able to say what caused what. Indeed, for the study at hand, while very well done, the study could not (and did not claim to have) demonstrated a causal relation. Indeed, the patients in the hypnotic group also had a higher incidence of asthma, cardiovascular diseases (including coronary disease, cerebrovascular disease, hypertension, heart failure, peripheral vascular disease), chronic kidney diseases, diabetes, obesity and chronic obstructive lung disease. All these conditions are well known to be associated with increased mortality and with insomnia, for which it is logical to assume that doctors might prescribe sleeping pills.

So, as the authors of this study noted in their discussion of the results, the question of causality cannot be claimed, and these (and other similar studies) may have simply observed that people with chronic illness are more likely to have insomnia (and this is certainly true) and, of course, more likely to die. The cause of death was generally not available on the database.

How Safe Are Sleeping Pills?

Of course, sleeping pills like any other pills all have potential side effects. However, the side effects are less common, and generally manageable, for the newer classes of medications. Some of the older types (especially the barbiturates) are well known to cause depression of the respiratory system, especially in larger doses. While benzodiazepines also suppress respiration, they do less frequently.

All sleeping pills are potentially dangerous when combined with alcohol. Some sleeping pills can have depression as a side-effect. Again, there were no data on how many of the deaths were suicide. All the sleeping pills can be associated with problems with thinking and motor skills the next day. That is why for patients taking the longer-acting sleeping pills (Lunesta, for example), we often ask that at least 8 hours be allowed for sleep. At follow-up visits, we always assess whether patients are having "carry-over" effects. Some of the sleeping pills may make sleep apnea worse (especially the barbiturates and benzodiazepines), and this could, in turn, be a risk for car accidents or cardiovascular disease. Some of the sleeping pills (Ambien, for one) have been shown to increase reflux of acid from the stomach. This could irritate the upper respiratory tract and potentially be a source of infection.

On the other hand, the FDA trials allowing the prescription sleeping pills to come to market, while tightly controlled, and not involving millions of people did not demonstrate increased mortality. Most of these studies do show that, at least in the short term, sleeping pills may be associated with improved sleep quality and daytime functioning.

Tolerance and addiction are always a potential with sleeping pills. This was especially a problem with heavy use of barbiturates and benzodiazepines. With the newer classes (the non-benzodiazepines and others) this is less of a problem for most people.

What Is the General Approach to Treating Insomnia?

This is actually a complex question. This is because insomnia is not a disease (usually), but the result of something else. Causes include physical ailments (most chronic ailments can cause insomnia), pain, psychological stress (acute and chronic), other medications, organic sleep disorders (for example sleep apnea, restless legs syndrome), and poor sleep habits. The general approach is to find out how long the insomnia has been going on (if more than 1 month it is called chronic). We also like to find out if there is something that triggered insomnia. We also ask about the patient's medical and mental health history as well as medications. The social circumstances are extremely important. For example, if a patient works three nights a week, it is not surprising that he/she cannot stay awake during the night shift, and cannot sleep during the day. We look for signs of organic sleep disorders. Finally, we obtain a detailed history of the patient's bedtime schedule, sleep habits and sleeping environment.

Sometimes, the cause of the insomnia pops right out at you. For example, if a patient takes a 3- to 4-hour nap in the afternoon or evening, it is not surprising that they cannot fall asleep at a reasonable hour. At other times the sleep specialist must dig a bit more. Sometimes (about half the time) an organic sleep disordered is suspected of playing a large role. In these cases, an all-night sleep study may be useful. Sometimes, patients keep diaries which may be very informative. So, you see, the issue rather complex.

As noted elsewhere on our website, treatment options depend on the underlying cause of insomnia, the presence of other problems, and individual patient preferences. We always advocate treatment of any underlying cause (be it in the physical or mental health realm). We always advocate optimization of the patient's sleep schedule and sleeping habits (sometimes this takes a lot of work). In many cases we are faced with the need to choose some therapy, either temporary or long-term depending on the case for symptomatic relief. Insomnia is a very distressing symptom, and has real implications for functioning during the day, and treating the symptom is definitely called for while the other issues are addressed.

The two major categories of symptomatic relief for insomnia include sleeping pills, and cognitive-behavioral therapy (described elsewhere in this website). Each of these approaches has its own advantages and disadvantages. For long-term treatment of insomnia as a symptom, we prefer a behavioral approach (if possible), but there are some patients for whom long term sleeping pills are acceptable. We certainly advocate an individual approach to treatment. Merely throwing pills at a patient is usually not the answer, certainly for a chronic problem.

What Is the Role of Sleeping Pills for Insomnia?

Hypnotics are tools. Like any tool, there are indications for use, and types. Hypnotics are often chosen on the basis of how fast they take action and how long their action lasts. For example, a short acting, rapid onset hypnotic may be indicated when the problem is going to sleep, where for sleep maintenance, a longer duration of action may be indicated. Also, interactions with other medical problems or medications must be taken into account.

For short term insomnia (jet lag, temporary life stressor), sleeping pills may be taken for a few days if needed, without a problem. Hypnotics may be useful for night-shift workers who have trouble sleeping in the day after a shift (combined, of course with other coping strategies). Patients who are chronically insomniac do need symptomatic treatment and choices (above) exist. The particular choice for a particular patient must be made on an individual basis, taking all the relevant factors into account. There is no one-size-fits-all approach and the appropriate treatment plan must be made by the patient with his/her physician or sleep specialist.

Should I Throw Away my Sleeping Pills?

There is no need to panic, or to toss the sleeping pills in the toilet. There is no certain evidence that sleeping pills caused the excess mortality observed, rather it is likely that conditions associated with mortality and that cause insomnia led physicians to prescribe sleeping pills. However, as noted above, alternatives exist. There is no reason to accept a lifetime on sleeping pills as a given.

Other avenues for evaluation and treatment of insomnia certainly can be explored with a health care practitioner knowledgeable in this terrible problem. Before throwing the pills away, patients on chronic sleeping pills should have a frank discussion with their health care practitioner about the issues. The practitioner and the patient can then make rational decision that suits that particular individual patient's needs.

Types of Hypnotics

The term hypnotic roughly refers to what are commonly called sleeping pills. These are medications taken prior to the sleeping period that are an aid to falling asleep and/or maintaining sleep. There are various types of medications out there. They differ in class, onset of action, duration of action, and potential risks. Here are some of the more common types. They are listed as the generic name first, and the brand name after. Most are available generically. These lists are not meant to be all-inclusive, but only representative.

  • Benzodiazepines ("benzos" the Valium class of medicines): These medications work on receptors in the brain called GABA (gamma-amino-butyric-acid). While Valium was the first of this type (and had a fairly long duration of action), there are others out there that are in more common use. These include temazepam (brand name: Restoril), triazolam (brand name: Halcion), lorazepam (brand name: Ativan), alprazolam (brand name Xanax), oxazepam (brand name Serax), chlordiazepoxide (brand name Librium), and clonazepam (brand name Klonopin). While the benzos have been commonly used as hypnotics, they are less so nowadays. This is partly because there are other effective hypnotics that don't have all the other effects of the benzos. These other effects include anti-anxiety effects and muscle relaxation, as well as some depression of the breathing centers (although this only in large doses). Some of the effects (like anti-anxiety and muscle relaxation) are desired in certain circumstances and may be the main reason they are prescribed.
  • Non-benzodiazepines: These are often called the Z-class because they all include the letter Z in the generic name. These medications also work on the GABA receptors, but are more specific for sleep-inducing than the benzos. These include Zolpidem (brand name Ambien), Zaleplon (brand name Sonata), and Eszopiclone (brand name Lunesta). Because their side-effect profile is a little better, and they don't have the same number of other effects, this class has become the most commonly prescribed.
  • Barbiturates: Include phenobarbital (Most common brand name Luminal), pentobarbital (most common brand name Nembutal), and secobarbital (most common brand name Seconal). While in the past, these were commonly used as hypnotics, because of side effects, primarily the possibility of severe depression of breathing, they are rarely used for this purpose today, although some members of this category are used as effective anti-seizure agents.
  • Melatonin like drugs: melatonin ("the hormone of the dark") is released by small glands in our brains called the pineal gland. This gland is an important part of the system which regulates our wake-sleep cycles and synchronizes it to the daylight—dark conditions in which we find ourselves. Essentially as light fades, melatonin is released and affects other areas of the brain, and other areas of the body, to push us into a nighttime mode. In the early morning, melatonin secretion stops. The whole system is keyed to blue light being detected in our eyes. There are many receptors in the body for melatonin. It is also fair to say, that we do not yet know the functions of all the melatonin receptors. In the US, melatonin is available as a food supplement in most health food stores (sometimes extracted from the pituitary glands of cows) and are not FDA-regulated as drugs. One drug ramelteon (brand name Rozerem) is available and affects certain melatonin receptors (types 1 and 2) known to be associated with sleep induction. Thus, ramelteon does not work on the GABA receptor in the brain.
  • Off-label antidepressants: Some of the antidepressant medications have soporific (sleep-inducing) properties. Sometimes, physicians will prescribe these as sleeping pills. A good example of this is trazodone (brand name Oleptro). While these are effective antidepressants, and depression is a major cause of insomnia, the long-term use in patients who are not depressed is certainly far from proven.
  • Over-the-counter sedating antihistamines: These are generally available without prescription and are sometimes used as sleep aids, although their effectiveness, especially in the long-term, is in doubt. This class of medications is often the ingredient in the nighttime version of many pain killers (like Tylenol and Advil). A commonly used medication in this class is diphenhydramine (brand name Benadryl), but there are many others.
  • Other over-the-counter sleep aids: There are various types of herbal remedies that are touted as sleep aids. One, valerian root (Valeriana officinalis), is available under various brand names for treatment of anxiety and insomnia. Effectiveness is not as well established as for the regular sleep aids. Interestingly, the valerian root contains within it a compound that resembles the benzos

See Dr. Scharf's interview on ABC World News about the dangers of sleeping pills.