SLEEP
March 1, 2008

The Treatment of Insomnia: New Developments

Andrew D. Krystal, M.D., M.S.
Dr. Krystal is the Director, Insomnia and Sleep Research Program, and Associate Professor with Tenure in Psychiatry and Behavioral Sciences, Duke University School of Medicine.

People tend to use the word insomnia casually, but insomnia is more than just occasional tossing and turning in bed. It is a debilitating, often chronic illness. To be diagnosed with true insomnia, you must have a problem falling asleep, staying asleep or getting enough rest from sleep that interferes with work or other everyday tasks. People with insomnia often find it difficult simply to get through the day.

Six of the ten most frequently prescribed insomnia drugs have never actually been studied for this use; the most frequently administered drug has been the subject of a single study, which, incidentally, suggested that it did not work.

A Common Problem That Is Little-Researched
Today, a surprising 10-20% of the U. S. population suffer from insomnia. Yet despite how common it is, many people with insomnia go untreated, and many commonly-used treatments are either not effective or not backed by scientific research. A quick look at the most common drug treatments given for insomnia in the U.S. in the year 2002 underscores this point. (See Figure 1). Six of the ten most frequently prescribed insomnia drugs have never actually been studied for this use; the most frequently administered drug has been the subject of a single study, which, incidentally, suggested that it did not work.



Figure 1.
Studies of Insomnia Prescriptions in 2002.
Figure 1

Figure 1 shows that a drug that was prescribed 2.75 million times in 2002 had been studied only once; between 0.5 and 1 million prescriptions of two other drugs were written without any study having been carried out; between 0.25 and 0.5 million prescriptions were written for three others, also without a single study supporting their use for insomnia.

For many years, there was very little research on insomnia. Recently, however, this has begun to change. A number of new studies are providing important new information that may lead to new and better weapons in the battle against insomnia.

Who Should Receive Treatment for Insomnia?
Here are the basics regarding the state of our current understanding of insomnia and its treatment:
  • Chronic insomnia interferes with the ability to work and to perform ordinary daily tasks.
  • Insomnia needs to be treated directly, even when it co-exists with serious medical and psychiatric conditions.
  • There are effective non-drug therapies.
  • Treating insomnia along with a related psychiatric or medical condition is not only possible, but can even improve the related condition.

Does Insomnia Interfere with Life?
Many people are significantly impaired by insomnia and could greatly improve their lives through treatment. Studies comparing chronic insomniacs to normal sleepers suggest that insomniacs experience more daytime sleepiness, fatigue, cognitive impairment, depression, anxiety, feelings of unhealthiness and problems with their social and work lives.

Obviously, many people without insomnia experience these symptoms from time to time. It is the severity of these symptoms and how much they interfere with a person's life and functioning that determines whether or not treatment for insomnia is needed. If you experience some or all of these in association with difficulty with your sleep and feel that they interfere with your daily functioning or quality of life, you should see your doctor or other medical practitioner.

When Insomnia Is Not the Only Problem
An estimated 80% of chronic insomnia occurs in connection with other medical or psychiatric disorders. The problem is that in the past, when insomnia was viewed as a symptom of another disorder, the need for direct treatment of the insomnia tended to be overlooked. The conventional idea was to try to cure the underlying medical or psychiatric disorder in the belief that the insomnia would improve along with the other symptoms.

The latest research suggests that insomnia needs to be treated directly, even when it occurs together with other medical and psychiatric disorders.

The conventional idea was wrong. The latest research suggests that insomnia needs to be treated directly, even when it occurs together with other medical and psychiatric disorders.13,14,15 The severity of insomnia can not only make a medical or psychiatric illness worse, buy it can actually serve as a sort of barometer that helps predict adverse outcomes and future episodes of both medical and psychiatric problems. In 2005, a NIH (National Institutes of Health) State-of-the-Science Conference panel urged doctors to consider new evidence (see below) that treating insomnia may also improve many associated conditions.

Treating Insomnia
There are both drug and non-drug treatments available for insomnia.

When doctors decide which treatment to recommend, they look to the scientific data for answers. Unfortunately, insomnia data are very meager for certain subgroups. In children and the elderly, for example, the risks of some insomnia drugs are likely greater than or different from the those for adults aged 21-65, who have been the focus of the vast majority of insomnia drug trials. In fact, there has yet to be a single published study of any drug for insomnia in children.

The same is true for those with medical and psychiatric conditions such as major depression, anxiety disorders, chronic pain, etc. Response to treatment and vulnerability to side effects probably vary quite a bit within this group. While solid data on many diseases have been lacking, specific studies have recently been done on the treatment of insomnia along with depression, generalized anxiety disorder, rheumatoid arthritis and fibromyalgia (See Table 5).

In one large study of insomnia occurring along with major depressive disorder (MDD), some subjects treated with fluoxetine for their depression were also treated for insomnia with the drug eszopiclone. Those given eszopiclone not only slept better but also had a faster and better response to the antidepressant.

Non-Drug Therapies
There are six main ways of treating insomnia without drugs: stimulus control therapy, relaxation therapy, paradoxical intention, sleep restriction therapy, sleep hygiene therapy and cognitive therapy. These are sometimes used alone and sometimes in combination.

Sleep Hygiene Therapy
Sleep hygiene addresses behaviors and other factors that may contribute to disturbed sleep (see Table 1).



Table 1.
Sleep Hygiene Therapy.
Caffeine Limit use. Eliminate evening/night intake
Alcohol Limit use. Eliminate evening/night intake
Nicotine Eliminate smoking at night
Exercise Eliminate exercising close to bedtime
Food/Liquid intake Eliminate excessive intake close to bedtime but encourage eating enough not to promote waking up due to hunger
Light Maintain a dark bedroom at night
Noise Eliminate noise in the sleep environment
Temperature Maintain comfortable temperature in bedroom

Relaxation Therapy
Relaxation therapy is a series of interventions aimed at decreasing the level of arousal (see Table 2).



Table 2.
Relaxation Therapies.
  • Progressive Muscle Relaxation
  • Biofeedback
  • Hypnosis
  • Guided Imagery
  • Meditation

Paradoxical Intention
Paradoxical intention is based on the idea that, for some people, trying to stay awake actually lessens the anxiety and effort associated with falling asleep. This therapy consists of lying in bed and to trying to stay awake as long as possible. Both relaxation therapy and paradoxical intention are primarily used to address difficulties falling asleep.

Stimulus Control Therapy
Stimulus control therapy was developed in order to change the pattern that can develop from having many sleepless nights and frustration and anxiety about sleep . This treatment involves trying to avoid being awake, frustrated or anxious when in the sleeping environment (see Table 3).



Table 3.
Stimulus Control Therapy.
  • Get out of bed when unable to sleep, or when frustrated or anxious about sleep
  • Do not worry, think or plan in bed
  • Go to bed only when tired to the point where sleep seems inevitable
  • Use the bed only for sleep and sex (no reading or watching TV)

Sleep Restriction Therapy
Sleep restriction therapy is an effective, if poorly named, treatment. When it is successful, the amount of sleep remains the same, while the amount of time spent in bed is reduced. The result is better consolidated, less fitful sleep. This is achieved by choosing consistent bed and wake up times that correspond to the average amount of sleep that you are actually getting. This is determined by keeping a sleep diary for 1-2 weeks. Other important parts of this therapy are eliminating naps and making sure you never to go to bed before the scheduled bedtime. It is also important not to go to bed, even after this bedtime, until you are sleepy. If the prescribed time in bed is too short, it is lengthened in 15-30 minute increments. If the insomnia continues, the time in bed is further curtailed by 15-30 minutes.

Cognitive Therapy
Cognitive therapy targets beliefs and thoughts that disturb sleep. Examples include the worry that not getting 8 hours of sleep on a particular night will have a disastrous effect on functioning the following day and the belief that waking up in the middle of the night is always a sign of sleep disturbance.

How Helpful are Non-Drug Therapies?
While it is commonly believed that non-drug therapies are completely harmless, there are some possible negatives that should be considered. Sleep restriction therapy may cause daytime sleepiness during the first several weeks or in instances where the prescribed time in bed is too short. There are also the cost of this therapy and the fact that it can take several weeks to work. In addition, unsuccessful treatment means more time before the insomnia is resolved. On the positive side, when these therapies do work, the results tend to be long-lasting.

In choosing to go the non-drug route, the most important considerations are your willingness and ability to commit to changing longstanding behaviors. Behavioral changes can be daunting, in the same way that eating less to lose weight is extraordinarily difficult for some people. Without a high level of motivation, behavioral therapies are doomed to fail. Furthermore, some insomniacs simply cannot carry out the required behavior changes. This includes those with medical illnesses that keep them bed-ridden and those with disorders such as severe major depression, dementia, mental retardation and schizophrenia.

Lastly, it is only in a subset of cases that behavior perpetuates insomnia. For those without behavioral perpetuating factors, cognitive and behavioral interventions are very unlikely to treat insomnia effectively.

Drug Therapies
There are a number of different types of drugs that are commonly used to treat insomnia. These include benzodiazepines, non-benzodiazepines, melatonin receptor agonists, antidepressants, antipsychotics and antihistamines. Of these, only the benzodiazepines, non-benzodiazepines and melatonin-receptor agonists are approved by the FDA for the treatment of insomnia.

Recently, a new drug, ramelteon, became available for insomnia. Other antidepressants used to treat insomnia include amitriptyline, doxepin, tri-imipramine, mirtazapine, nefazodone and trazodone. Antipsychotics can also enhance sleep; those most commonly used to treat insomnia are quetiapine and olanzapine. Anti-histamines are the most commonly used over-the-counter sleep aides.

In deciding which of these is right for you, it is necessary to discuss with your doctor whether a particular drug has been shown to be effective for the type of insomnia you are experiencing. As discussed above, only the FDA approved drugs (benzodiazepines, melatonin receptor agonists and non-benzodiazepines) are backed by hard science. Table 5 lists the drugs that have been proven effective in treating insomnia.



Table 4.
Studies Demonstrating Insomnia Efficacy.
Agent Sleep Onset Sleep Maintenance Longest Controlled Trial Older Adults
Benzodiazepines
Triazolam 0.25 mg +   4 Weeks +
Triazolam 0.5 mg + + 2 Weeks +
Flurazepam 30 mg + + 4 Weeks + (15-30 mg)
Estazolam 1/2 mg + + 2 Weeks  
Quazepam 30 mg + + 2 Weeks  
Temazepam 30 mg + + 8 Weeks + (7.5-30 mg)
Non-Benzodiazepines
Zolpidem 10 mg +   5 Weeks* + (5 mg)
Zolpidem CR 12.5 mg + + 3 Weeks  
Zaleplon 10 mg +   5 Weeks + (5-10 mg)
Eszopiclone 2/3 mg + + 6 Months + (2 mg)
Melatonin Receptor Agonists
Ramelteon 4-32 mg +   5 Weeks +
Antidepressants
Doxepin 25-50 mg + + 4 Weeks  

Table 5 lists therapies (both drug and non-drug) that are proven effective for insomnia when it occurs with another condition.

As with all drugs, side effects are listed on the FDA approved label. Given the same dosage of medication, there is a greater likelihood of side effects in older adults. Principal side effects of benzodiazepines and non-benzodiazepines are sedation, dizziness, amnesia and ataxia (clumsiness). Antidepressants and antipsychotics can cause sedation, dizziness and low blood pressure. Over-the-counter sleep medicines can cause daytime sedation and dizziness.

Follow-up Is Key
For non-drug therapies, follow-up with your doctor is needed in order to work through the inevitable difficulties of any attempt to change behavior. The role of follow-up in drug therapies is no less important. Re-evaluation is needed to check if the prescribed medication is effective and to deal with any side effects. Often, adjustments in dosage are needed or a different drug needs to be prescribed.

Once drug therapy is begun, there is no easy way of determining when the insomnia has been cured. As a result, it is necessary — typically every 2-3 months — to try stopping the drugs.

Another crucial part of follow-up is to the decision to stop therapy. We currently have no way of determining how long a particular case of insomnia is likely to last. Also, once drug therapy is begun, there is no easy way of determining when the insomnia has been cured. As a result, it is necessary — typically every 2-3 months — to try stopping the drugs. This should be done with a very gradual tapering off and only under a doctor's supervision.

As seen in Table 5, only a few anti-insomnia drugs have been proven effective for periods of over one month and only one has been evaluated as long as six months. However, studies have shown that for some medications dependence is unlikely and that treatment, even as long as six months or more, can be safe and effective.

Conclusion
It is an exciting time for insomnia research. Our understanding of insomnia is evolving rapidly. We now appreciate that insomnia can cause severe impairment and that insomnia must be treated directly, even when it co-exists with a serious medical or psychiatric illness. Studies have established that non-drug therapies can be safe and effective for some people and that, when properly monitored by a doctor or other medical professional, long-term drug therapy does not inevitably lead to dependence.

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