Pharmacotherapy in Managing Insomnia
Pharmacotherapy in Managing Insomnia
Assessing Patient Needs and Outcomes
Benjamin Chavez, PharmD
Nova Southeastern University
US Pharm. 2005;2:HS-23-HS-26.
Insomnia is a condition that affects nearly everyone at one point or another in his or her life. In a 1996 Gallup survey, 49% of adults said they were dissatisfied with their sleep at least five nights per month.1 It is estimated that up to 40% of adult Americans have intermittent insomnia, while 10% to 15% have long-term sleep difficulties.2 These numbers increase with age. Reports have shown that older adults report more sleeping disturbances than younger adults.3
The typical complaint of a patient with insomnia is either difficulty falling asleep or difficulty staying asleep. In the older population, they tend to report more trouble falling asleep, sleeping less at night, waking more often during the night, waking up earlier than they would like, and feeling tired during the day, while younger adults tend to complain more of trouble falling asleep.3
Insomnia can be the result of many things, including stress, acute and chronic medical conditions, loss of a loved one, psychiatric illnesses, life changes, poor sleep habits, or certain medications. Insomnia caused by stressful situations or a change in setting, such as jet lag or recent move, are usually transient and short-term. By definition, transient means occurring two or three nights, and short-term is duration of less than three weeks. Insomnia lasting longer than one month is considered long-term, requires a thorough assessment, and should be suspected to be the result of a medical or psychiatric condition.
Sleep problems can worsen if not treated properly and promptly. Self-medicating with over-the-counter medications can lead to adverse effects or worsening of the insomnia. Improper assessment of a patient's insomnia and its cause can also lead to unresolved problems.
Insomnia is an important condition that must be assessed and treated appropriately in order to assure good long-term outcomes and avoid any complications from the sleep disorder. A lack of sleep can cause the patient to be fatigued and inattentive the next day. This may lead to falls and injuries, which is of particular concern in the elderly. Lack of sleep can also lead to falling asleep on the road and causing a car accident, or being unable to pay attention at school or work and therefore not being able to perform as well as one would expect. Even more serious, insomnia can cause a patient to become overly stressed, leading to depression, anxiety, or other mental illnesses. To make matters worse, these same mental illnesses could be the cause of the patient's insomnia, which are then exacerbated by the lack of sleep, and lead to the formation of a vicious cycle.
Causes of Insomnia
Insomnia can be categorized as primary or secondary. The main criterion for primary insomnia is that any other medical condition, psychiatric illness, or other substance is not the cause of the sleep disorder. The majority of insomnia cases result from one of the reasons previously listed, and are therefore categorized as secondary insomnia. For this reason, primary insomnia is rare.
The causes of secondary insomnia can be broken clown into four main categories: situational, medical, psychiatric, or pharmacologic. Examples of situational causes are stress, recent life changes, moving to a new home, starting a new job, loss of a loved one, or poor sleep behavior. Insomnia caused by one of these situations is usually transient and resolves on its own after the person overcomes or fixes whatever the initial problem may be. Jet lag or work-shift change can also cause transient, short-term insomnia.
Medical conditions that can cause insomnia include acute or chronic pain, gastroesophageal reflux disease (GERD), obesity, sleep apnea, heart disease, restless leg syndrome, lung disease, or memory problems. All of these medical conditions can cause some type of discomfort or change within the body resulting in loss of sleep. For example, in a disease such as Alzheimer's disease, deterioration of the sleep-wake cycle can occur. With sleep apnea the patient may wake up several times throughout the night due to not being able to breathe properly, and as a result does not get sufficient sleep. This is why it is important to do a complete and thorough medical examination when assessing a patient's insomnia, especially in the elderly population. In a 2003 survey completed by the National Sleep Foundation, the results showed that the prevalence of sleep problems increased dramatically from 36% to 52% when the patients had at least one medical condition.4
When a medical condition is present along with insomnia, that underlying condition should be treated first. By treating the underlying problem, the insomnia should also be corrected. If it does not, then another assessment should be done, including the patient's sleep habits, and his or her treatment should be adjusted accordingly. It would be optimal if the insomnia can be treated without any pharmacologic intervention. Behavior modification, which will be discussed in the next section, is a good way to correct many sleep complaints.
Psychiatric illnesses can also present with insomnia as one of their symptoms. Depression, anxiety, bipolar disorder, and schizophrenia can all present with insomnia.
Again, it is important to treat the underlying psychiatric condition with the appropriate therapy, and not to simply treat the insomnia. Ignoring the underlying problem could only make matters worse. A thorough examination and history of the patient is needed to rule out any psychiatric illness. If needed, refer the patient to a mental health practitioner for further evaluation.
Pharmaceuticals are another cause of insomnia. Drugs and substances that can cause insomnia include decongestants, steroids, antidepressants, diuretics, steroids, beta-agonists, caffeine, alcohol, and other drugs of abuse. It is important when doing an assessment to ask the patient what, if any, medications he or she is taking. If the patient is taking a medication that could be the cause of the insomnia, then either change the time the person is taking the drug (i.e., if the patient takes it at night, tell the patient to take it in the morning), or change to another medication. A pharmacist can be particularly helpful in this area. Dietary habits of the patient should also be assessed, such as caffeinated beverages, alcohol intake, or dietary supplements. Any stimulating substance, such as caffeine, should be avoided at least eight hours prior to bedtime.
Before initiating treatment for insomnia, it is important to perform a full assessment of the problem. A full medical history is the first step to this assessment. This can help pinpoint any underlying medical conditions that could be causing the sleep disorder. If there is a medical or psychiatric condition that is causing the insomnia, that underlying condition must be treated first. If the sleep disturbance is not caused by a medical or psychiatric illness, then one should try to determine what could be the cause. Finding out what the patient thinks is the cause of his or her insomnia may lead to better treatment of the problem. Table 1 lists questions that should be asked of the patient during the assessment. One must determine whether the main complaint is falling asleep, maintaining sleep throughout the night, waking up too early, or waking up not feeling refreshed. Another crucial part of an assessment is determining if the patient's current sleep habits could be the cause of the sleep problem. If the patient displays poor sleeping behavior, then nonpharmacologic treatment, or behavior modification, should be first-line treatment. It is also important to determine what the patient's goals of treatment are. This will help to tailor an appropriate treatment plan.
Behavior Modification (or Nonpharmacologic Treatment)
The first step in correcting a sleep problem should be to initiate nonpharmacologic treatment. This is accomplished by modifying the patient's behavior that may be affecting his or her sleep. Common behavior modifications include establishing a regular sleep schedule, avoiding daytime naps, and limiting caffeine or nicotine intake. Another behavior which can be corrected is improper self-medicating. Many patients will decide to self-medicate with alcohol in order to fall asleep. Although alcohol intake may cause the patient to fall asleep, the sleep is usually not restful and rebound insomnia can occur. In some cases, cognitive or psychotherapy may be options as well. Examples of nonpharmacologic therapies are listed in Table 2.5
There are certain circumstances where pharmaceuticals can play a role in the treatment of insomnia. After nonpharmacologic options have been exhausted, and the patient's complaints have not been adequately addressed, pharmacologic therapy may be instituted. A pharmaceutical agent can be helpful to use for a brief period of time while patients modify whatever poor sleep behaviors they may have. Short-term treatment with sedative hypnotic drugs may also be beneficial while a person is adjusting to a new situation or coping with a stressful event. However, it is important to remember that the use of sedative-hypnotics should be limited to short periods of time and only intermittently.6
Prescribing sleep agents should be based on the severity of the patient's complaints and the impact the sleep problem has on his or her daily functioning. The ideal sleeping agent would have a quick onset, duration of action long enough to provide sleep for the entire night but not too long to cause next-day sedation, no tolerance or withdrawal, be safe from overdose, and cause minimal side effects.7
Barbiturates, such as pentobarbital and secobarbital, were the drugs of choice for insomnia in the 1950s and 1960s. However, they have long since fallen out of use due to their quick development of tolerance, high overdose potential, and their risk for physical and psychological dependence. The most well known class of prescription drugs for the treatment of insomnia are the benzodiazepines (BDZs). Benzodiazepines help in insomnia by shortening sleep latency, decreasing the number of awakenings throughout the night, and increasing total sleep time. However, they also alter the sleep stages by decreasing stage 4 sleep, which is the restorative stage of sleep, and decreasing REM sleep.8 All BDZs share the same side effects of excessive sedation, psychomotor retardation, decreased concentration, and anterograde amnesia.5 Tolerance to the BDZs can occur in as little as two weeks.9 When selecting a BDZ, it is important to choose one with an appropriate pharmacokinetic profile that matches the patient's needs. If the patient has trouble falling asleep, then a quick-acting BDZ such as triazolam might be a good choice. If the patient's main complaint is early morning awakenings or waking up throughout the night, one might consider a longer-acting BDZ such as temazepam. BDZs should be used with caution in the elderly due to the increased risk of excessive sedation leading to falls. If a BDZ is used in an elderly patient, it would be best to choose one with no active metabolites and a relatively short half-life.
A newer class of agents, described as the non-benzo BDZs, is becoming a more frequent and popular choice in the treatment of insomnia. The two drugs in this class are zolpidem and zaleplon. Zolpidem belongs to the imidazopyridine class, while zaleplon belongs to the pyrazolopyrimidine class. However, both of these drugs share the same mechanism of action. Zolpidem and zaleplon act selectively on the BDZ omega-receptor subtype.
By acting on this specific receptor, they reduce the anxiolytic, muscle relaxant, and anterograde amnesic effects of the BDZs, but still maintain the sedative properties. Zolpidem and zaleplon both have very short half-lives of about two hours and one hour, respectively, therefore causing very little next-day sedation. Zaleplon's peak effects can be seen in about one hour, and its duration is about four to five hours, making it optimal for patients to take in the middle of the night and still wake up four to five hours later without any excessive sedation.9 Zolpidem also has a rapid onset of action and a duration of six to eight hours, which is still short enough to cause little next-day sedation. Another favorable property of these drugs is that they do not decrease delta sleep or REM, unlike BDZs, but still decrease sleep latency.10 The most common side effects of zolpidem are dizziness and gastrointestinal complaints. The most common side effects of zaleplon are dizziness and headache.5 The side effect profile of these drugs, along with their pharmacokinetic properties, makes them a favorable choice for the treatment of insomnia.
Antidepressants with sedating properties are another alternative treatment for insomnia. Drugs such as amitriptyline and nortriptyline, which have antihistaminic properties, were used more frequently in the past, but have lately decreased in use because of their unfavorable anticholinergic side effects and the development and marketing of newer agents.10 Antidepressants such as trazodone and mirtazapine, when used at low doses, are reliable sedating agents. Trazodone has sedating properties at doses much lower than those used for depression. Trazodone has been shown to decrease sleep latency while increasing delta sleep and having very little effect on REM sleep.11 Priapism is a serious but rare side effect associated with trazodone. Mirtazapine also has sedating properties, but that effect decreases with higher doses. Patients should be informed that mirtazapine may cause an increase in appetite, leading to weight gain. Mirtazapine should be used with caution in patients with hypertension. Overall, these antidepressants are viable options for patients with insomnia due to depression or insomnia due to antidepressant therapy.
There are not many over-the-counter (OTC) agents for sleep. The most common OTC product is diphenhydramine, an antihistamine with sedating properties. Diphenhydramine is found in many OTC sleep, cold, and allergy medications. However, due to its anticholinergic side effects and excessive next-day sedation, it is not a favorable a choice for chronic use. Its use should be avoided in the elderly due to the increased risk of confusion and falls. Doxylamine is another OTC antihistamine, similar to diphenhydramine, and is found in Unisom and Nyquil.
Valerian root is an OTC herbal product that has been shown to decrease sleep latency and increase delta sleep at doses of 400 mg.12 However, it is important to remember that the FDA does not regulate herbal products, and therefore the quality of the product cannot be assured. Kava-kava is another herbal product for insomnia, but the FDA no longer recommends its use due to a recent advisory that it may cause severe liver toxicity.13
Melatonin, a hormone released by the pineal gland at night to promote sleep, is available as an OTC product marketed as a sleep aid. It may be of some use in patients experiencing jet lag, work-shift change, or blindness.14 However, results from clinical trials of patients using melatonin for insomnia have been inconsistent.15,16 It is important to inform patients that the FDA does not regulate the quality of melatonin, and therefore, it is not subject to quality control.
Insomnia is a condition that affects nearly everyone at some point in his or her life. However, primary insomnia is rare. Most cases of insomnia are due to an underlying medical condition, a psychiatric illness, a recent stressful situation, or are secondary to a substance or medication that a patient is taking. A complete history and a thorough assessment are crucial in order to properly treat insomnia. If the insomnia complaint is due to an underlying condition, that underlying condition should be treated first. The patient's sleep hygiene should be assessed as well. If the patient displays any unhealthy sleep behaviors, then he or she should be educated properly. Behavior modification should be first-line therapy for insomnia.
Pharmacologic treatment is also an option for the treatment of insomnia. The use of zaleplon and zolpidem should be reserved for short-term transient use, unless a compelling indication exists for long-term treatment. There are also other pharmacologic options for insomnia, such as antidepressants and some OTC agents. A short course of treatment with a sedative-hypnotic while the patient modifies the unhealthy behavior or copes with a stressful event is acceptable. Most importantly, working together with the patient, conducting a thorough assessment, and establishing what his or her goals for therapy are will help to tailor the treatment and lead to more favorable outcomes.
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Time is the school in which we learn, time is the fire in which we burn.
~ Delmore Schwartz
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