36 SLEEP MEDICATIONS [Rev 6-21-2018]
One of the treatment suggestions in Step D1 (Section 46)
The issue of the impact of medications on sleep comes up in different ways
- Drugs the person is taking that can have an impact on sleep.
- Drugs the person is taking specifically to manage sleep but that ought to be reconsidered.
- Drugs we might suggest to help manage sleep.
Most treatments of the issue of medications are from one of these perspectives. This section won’t consider the use of medications for other purposes, eg.: using antidepressants in the treatment of depression.
36a. All Medications that the Person is Already Taking
When the person is having difficulty with sleep, we could ask, among other things, what medications he/she is taking, and for what purpose. It may be that a drug the person is taking for a symptom, illness or disability has insomnia as a side effect. Or we could have asked already, as a way of exploring his/her treatment of another issue or disorder.
We need to be able to look up a wide range of medications alphabetically for their likely effects on sleep, including whether they are energizing and what the common dosages and half-lives are. There are many resources on the Internet for this, including Medscape, drugs.com, the National Institute on Drug Abuse, WebMD and Wikipedia. For a list of FDA-approved sedative-hypnotics with links to descriptions of each, go to the FDA site.
If there is a likelihood that the person’s current medications are interfering with sleep, it would be helpful to see if alternatives are available. Then we could ask whether the person had tried each and what the reaction was. This could also be helpful in a discussion with the patient’s physician.
Often, reports on medications will indicate whether they are energizing or sedating. Whenever possible, it is better to take energizing medications early in the day and sedating medications toward the end of the day. That way, the side effects better match the person’s normal circadian (day-night) cycle.
36b. Prescription Drugs for Sleep
A distinction can be made between hypnotics, which induce sleep, and sedatives, which are used to relieve tension and anxiety. However, the most common form of inducing sleep is to start with reducing tension; and it is common to talk about sedative-hypnotics as a single class of drugs. This is the approach taken at the FDA web site.
General problems of using medications to go to sleep include:
- They are a seductive answer to people who don’t want to wait, to work on the problem, to look at other issues in their lives.
- They are the go-to solution for many physicians.
- Advertising makes them seem both reasonable and effective
Many people prefer a treatment that involves medication – drugs are widely available, they are often cheaper and easier to initiate than psychological or behavioral treatments, and they seem to involve less thought and action from the patient.
But
- They commonly only treat the symptom and not the cause.
- They are not as effective as psychological or behavioral treatments
- A person can become dependent on them
- They interfere with a person’s performance the following day, even when they appear to aid in sleeping
- They lose effectiveness over time, leading to increased doses, a return of insomnia, discouragement and a sense of failure.
In general, except for patients with primary or idiopathic insomnia (Section 15), sleep medications should be considered to be a short-term solution pending a change in the person’s situation or until other, non-medical treatments can be instituted. (Reite, Weissberg and Ruddy, p.86)
A wide variety of medications are prescribed for insomnia. These generally fall into four broad classes
- Benzodiazepines, including Xanax and Ativan
- Non-benzodiazepines, including Ambien and Sonata
- Sedating antidepressants, including Elavil and Desyril
- Anticonvulsants and antipsychotics, including Zyprexa and Neurontin
Sleep medications commonly sedate the person’s cortex and help to lose consciousness. So the person may think that a particular drug is effective in managing insomnia. However, these drugs also interfere with other brain activities that normally occur during sleep. See Section 4 for more on this problem.
BENZODIAZEPINES
This is the class of medications that people commonly refer to as “tranquilizers,” because they are often used to deal with daytime anxiety. As sleeping aids, they may be prescribed at higher doses. According to McCall (p.403) there are no fundamental differences between benzos approved for insomnia and those not approved, other than pharmokinetics and route of administration.
Commonly prescribed are Valium, Librium, Ativan, and Xanax. People who use these drugs often believe that they induce sleep. However, objective studies show them to have no advantage relative to placebos (Walker, 284).
They are generally considered safe if used as prescribed (Hauri and Linde, p.187; Jacobs, p.32). They can help a person get to sleep, with little effort, but there are drawbacks.
They…
- often have both anxiolytic and sedating properties.
- may lead a patient to confuse insomnia with anxiety
- may have long half-lives that affect the person into the next day, with sleepiness and cognitive and motor impairment (Roehrs and Roth, p.388)
- may affect Stage I (REM) and Stage III (deep) sleep adversely.
- can depress breathing. This can be of special concern for people with a weak respiratory system or sleep apnea (Hauri and Linde, p. 181). People with these issues may have worse sleep with the medication than without.
- can produce tolerance, over time requiring larger doses to be effective. However, Krystal (p.379) reports that some patients can get relief for up to a year, without requiring an increase in dosage. On the other side, Jacobs states that there is no scientific evidence for their effectiveness for more than 4-6 weeks of nightly use.
- can lead to both physiological and psychological dependence. However, according to Krystal (p.377), there is little abuse potential in insomnia patients who don’t have a history of substance abuse.
Also,…
- Discontinuation often leads to rebound insomnia, even after using them for as little as one or two nights (Roehrs and Roth, p.389).
- When a person stops abruptly after using one for a long time, it can lead to withdrawal symptoms – nervousness, headaches, and possibly seizures. Benzos should be tapered slowly.
Jacobs (p.32) refers to research finding that people with insomnia who took sleeping pills still took an average of 46 minutes to fall asleep. Thus, he argues, they don’t lead to falling asleep quickly. At the same time, he reports that they cloud thinking and memory, leading people to believe that they slept more than was the actual case. Placebos, on the other hand, typically don’t cause these same negative consequences. The obvious answer is for a person who wants a medical solution to take a placebo.
The Half-Lives of Medications
Any medication can be categorized in terms of its half-life, an indicator of how long its effect lasts. It becomes effective by first getting into the person’s bloodstream, and then being distributed throughout the body. As the blood is repeatedly circulated by the heart, the medication passes through the person’s liver and is partly converted to other chemicals that usually don’t have the desired effect. In this way, the original compound is gradually rendered ineffective.
The time it takes the liver to convert half of the original compound to ineffective byproducts is the half-life of the medication. A compound with a half-life of four hours is half as concentrated in the person’s blood after four hours, and presumably, half as effective in doing its job.
The process continues. For the same medication, the next four hours reduce what’s left by 50%, so that after eight hours, the effective concentration is one-quarter what it was at maximum.
This gives us a way to classify medications. The longer a medication’s half-life, the longer it stays effective in the person’s body. In terms of sleep medications, if the desired effect is to make a person tranquil or drowsy, then the longer a medication’s half-life, the longer the person is likely to be drowsy or sleepy.
There is no exact half-life for a drug, because it depends on the ability of a person’s liver enzymes to convert the drug to an inactive metabolite. But averages are available.
Half-Lives of Benzodiazepines
It is common to classify benzodiazepines as having long, intermediate, or short half-lives. It gives us a starting point for guessing whether a particular drug is being used effectively with a patient. For a table of benzodiazepines that includes their half-lives, see this Wikipedia listing.
Patients may not be aware of some of the effects of medications, and a careful examination of the medication a person is taking may help to explain them. In general, in choosing a benzodiazepine, the choice should include having the shortest effective half-life and the lowest effective dose possible. Even so, it is safest to consider medication to be a temporary or short-term boost in the direction of better sleep for one or a few nights at most (Roehrs and Roth, p.393)
Benzos with long half-lives in common usage include flurazepam (Dalmane; 40-150 hours) and quazepam (Doral; 39-120 hours). If a person is taking one of these at bedtime, and if it is effective, then he/she should expect to be drowsy eight hours later and throughout the next day, as most of the dose is still in the blood stream.
One benzodiazepine with a short half life is triazolam (Halcion; 2-5 hours). If the problem is either falling asleep or early interrupted sleep, this could be helpful. Because of its short half-life, it is less likely to cause drowsiness the day after taking it. However, a single dose at bedtime might not be enough to help a person sustain sleep for a full night.
Benzodiazepines with intermediate half-lives may last through the night and have less tendency to lead to drowsiness the next day. Two in this category are estazolam (ProSom; 10-31 hours) and temazepam (Restoril; 4-10 hours).
Dangerous Benzodiazepine Interactions with Alcohol and Other Drugs
If a person is currently taking other drugs or using alcohol, there are serious dangers. The FDA posts the following notice:
Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death.
For a discussion of pharmacological treatments of substance abusing or recovering patients, see Conroy, Arendt and Brower. In any case, patients should be cautioned not to exceed prescribed doses.
NON-BENZODIAZEPINE ANXIOLYTICS
More recently, several nonbedzodiazepine medications have been developed that activate the benzo sleep receptors in the brain but have fewer of the other benzo side effects, such as tolerance and changes in the person’s sleep architecture (Reite, Weissberg and Ruddy, p.82-83). This group includes Zaleplon (Geodon and Sonata, 1-1.5 hour half-life ), Zolpidem (Ambien, 1.5-2.5 hours), ramelteon (Rozerem, 1-2.5 hours) and eszopiclone (Lunesta, 6 hours).
Of these, Krystal, (p.378) zolpidem (Ambien), zolpidem CR, zaleplon (Geodon) and eszopiclone (Lunesta) for sleep-onset insomnia, and estazolam, zolpidem CR and eszopiclone for sleep maintenance problems.
Walker (pp.285-9) argues against using these medications, citing large matched-group studies showing that people who regularly took them had four times the risk of dying over a 2 ½ year period. The increased death rate was due largely to infection (normal sleep restores the immune system), auto accidents (from next-day grogginess), falls at night, heart disease and strokes.
Most authors who recommend these recommend them as very short-term boosts, used while a person’s situation is changing or other non-medical treatments are instituted.
ANTIDEPRESSANTS
There is widespread use of sedating antidepressants off-label for treatment of chronic insomnia. The choice seems especially relevant when the person complains of daytime anxiety or depression as well.
Some antidepressants, such as flouxetone (Prozac) and protriptyline (Vivactil) are generally energizing (Jacobs, p.37; Morin, p. 159). However, most are at least somewhat sedating for most people. They do differ in how sedating they are. Some are prescribed for insomnia because of this sedating side effect: namely, trazadone (Desyrel), amitriptyline (Elavil), mirtazapine (Remeron), and doxepin (Sinequan). They all have other side effects that can be upsetting to some patients, but they are typically prescribed in lower doses for sleep than for depression as the primary symptom, so the other side effects may be less troublesome.
Even so, antidepressants typically have long half-lives because they have been selected to treat a long-term symptom. The half-life of amitriptyline is reported as 20-30 hours, of doxepin is10-25 hours, and of mirtazapine is 22-40 hours (McCall, pp.401-402). Thus we should expect next-day continuance of any effect they are used for at bedtime – like drowsiness.
Other side effects can include orthostatic hypotension and dizziness. According to First and Tasman (p.458) and Reite, Weissberg and Ruddy (p.85), these medications may be helpful in depressed patients with insomnia, but they have not been shown to be helpful to patients who are not depressed.
OTHER SEDATING MEDICATIONS
According to McCall (pp. 397-399) there has been a double incentive to prescribe off-label for insomnia: (1) it has been relatively easy for physicians to extend the use of medications to unapproved used, because the FDA accepts the concept that the local prescriber has information that could make it appropriate; and (2) the process of getting medications approved by the FDA has both restricted choices and limited the flexibility of physicians in using approved drugs. This does not necessarily mean that off-label uses lead to better control of patients’ insomnia. There is also very little information about the safety of these drugs, which should make one think carefully before recommending them.
An additional problem is that there is limited effectiveness research, much of which is with special populations – like people anticipating surgery. McCall (p.398) says, “…in the absence of testing done directly in the population of interest, it is hazardous to predict how a medication might work…”
Two atypical antipsychotic medications are sometimes prescribed in low doses for insomnia. Quetiapine (Seroquel) and Olanzapine (Zyprexa) have had some promising results.
Among anticonvulsants, gabapentin (Neurontin) may relieve pain-related sleep disturbances (McCall, p. 404-405); and Valproic Acid (Depakene) may relieve some insomnia realted to manic episodes. (McCall, p. 405). It is not clear whether these medications are helpful to patients without chronic pain or mania.
McCall concludes with a set of recommendations. Off-label treatments are rarely supported. Exceptions include:
- Insomnia and depression: try Desyrel (trazodone), Remeron (mirtazapine) or tricyclic antidepressants
- Psychosis and insomnia: try Seroquel (quietapine) or Zyprexa (Olanzapine)
- Anxiety and insomnia: try Ativan (lorazepam), Klonopin (clonazepam) or Xanax (alprazolam)
- Insomnia and periodic limb movement: try Klonopin (clonazepam)
- Insomnia and bipolar disorder: try Depakene (valproic acid)
- Pain or alcohol abstinence and insomnia: try Neurontin (gabapentin) or pregabalin.
36c. Self-Medication
People who can’t sleep often look to alcohol, marijuana, melatonin, and over-the-counter preparations for relief.
OVER-THE-COUNTER
Many sleep preparations include antihistamines as primary ingredients.
There are several drugs in this category, the most common of which is diphenhydramine. A few studies with special populations have produced subjective reports of effectiveness in both falling asleep and sleep maintenance. However, with a half-life of 7-12 hours, it tends to produce grogginess the day after, along with dry mouth, constipation and reduced cognitive functioning (Neubauer and Flaherty, p.418-419).
There is little systematic evidence for their effectiveness in treating insomnia in the general population (First and Tasman p.458; Roehrs and Roth, p.392), but they can make a person drowsy and groggy, which some people can use to help fall asleep (Hauri and Linde, pp.190-191). Tolerance develops after a few days, and after that, their effectiveness, if any, is mostly psychological.
Hauri and Linde (p. 191) suggest that two aspirin and a glass of water at bedtime can help induce relatively normal sleep in some people. Here also, the effect wears off after a few days, so the treatment, if it helps, should be used infrequently .
Many herbal sleep preparations include melatonin, which is discussed in Section 22
Others include valerian root, kava kava, St John’s Wort, and chamomile tea. These are discussed by Hirshkowitz and Smith (pp. 82-83) and Neubauer and Flaherty (pp.420-423). They may appear benign to consumers because they are unregulated as medicines. However, because they are unregulated, the purity and concentration can vary considerably and unpredictably. In addition,…
- Valerian root has been reported to help with sleep onset and length of sleep time for some patients. But the effect is apparently dose-dependent, an side effects can include headaches, indigestion and restlessness, and it may interact with alcohol.
- Kava kava has been reported to help some people sleep, in some special populations. However, it has been associated with liver toxicity in some people, and it has been banned in the European Union and Canada.
- St Johns Wort apparently affects seratonin, norepinephrine GABA and dopamine, and has been studied as a treatment for depression. It has apparently not been studied in treatment of insomnia in normal populations. The major concerns are interaction with other medications that a person may be taking (Neubauer and Flaherty (p.422).
- Many people like chamomile tea as a sleep aid. Major drawbacks seem to be that some people are allergic to it, and that it can increase the risk of bleeding in people who are taking aspirin or other blood-thinning medications (Hirshkowitz and Smith 83).
Neubauer and Flahertry quote the American Academy of Sleep Medicine (p.422):
“There is only limited scientific evidence to show that herbal supplements are effective sleep aids. Because these products may be marketed and sold without FDA approval and may involve dangerous side effects or adverse drug interactions, they should be taken only if approved by a physician.”
36e. Short-Term Versus Long-Term Medication
Most medication recommendations are for temporary relief, with the purpose of breaking a pattern of sleepless and worry, and preparing the person to move on in a more effective way.
Side Effects
All drugs have side effects. People take them because they are seen to change physical, neurological or psychological experience. They do this by affecting targeted cells and organs. But they get to the target organs through the bloodstream, which goes to all parts of the body. A side effect is the impact of the drug on an unintended organ, and sometimes the impact can be detrimental even if unexperienced. The shorter the time the drug is used, the less risk of permanent damage.
Rebound
Hauri and Linde point out (p. 177) that all sleep medications have a physiological rebound effect, called “rebound insomnia”. When the person stops taking the drug, his or her insomnia commonly returns, in a worse form than before. The longer the person has been dependent on a drug, the greater the likelihood of rebound on stopping it.
Switching Drugs
Hauri and Linde also make the point that it doesn’t help to switch from one drug to another, because they are generally “cross tolerant”, each continuing the dependence begun by the previous drug.
36f. Placebo Effect
Many treatments are effective in part because a patient expects them to be effective. When it appears that a person is benefiting from an unlikely treatment, it is reasonable to ask more about the treatment and the results. However, if some medication appears to be helping a patient, and there are no apparent harmful consequences, it might be best to accept the patient’s report and move on to other issues.
36g. Treatment
In most cases, medication is seen as a temporary solution to help a person begin to take control of sleep loss and its consequences. Ideally, diagnosis and treatment of situational, interpersonal or psychological issues will be effective enough that medication can quickly be discontinued.
However, ending the medication can have unexpected consequences and should be done with the advice of the patient’s physician or other prescriber.
This can be done by either you or the patient. If you make the contact, be sure to have all the relevant information at hand, along with a release from the patient to make the call.
36h. Brief reference
Generic Name Street name type half life
Hydroxyzine Atarax antihistamine 3 hours
Quetiapine Seroquel antipspychotic
Olanzapine Zyprexa antipspychotic