Management of Insomnia by xumiaomaio

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									         continuing education



         Management of Insomnia
         By Ariane Conrad, PharmD




  U                       pon successful completion of this article,
                          the pharmacist should be able to:
                          1. Describe the characteristics and signifi-
                             cance of insomnia.
                          2. identify the goals of therapy for the man-
                             agement of insomnia.
         3. Describe the non-pharmacological techniques recom-
            mended for the management of insomnia.
         4. Describe the medications and their typical dosages,
                                                                               due, at least in part, to underreporting of symptoms
                                                                               to their physicians.
                                                                                    insomnia has been estimated to be associated
                                                                               with high health care utilization costs. Direct and
                                                                               indirect costs of chronic insomnia were estimated
                                                                               to be $10 billion annually in 2005. As insomnia is
                                                                               often associated with complaints due to another
                                                                               disease state, it is difficult to separate the costs as-
                                                                               sociated with insomnia alone. However, it has been
            clinically significant or commonly encountered side ef-            shown that people with insomnia have higher rates
            fects and drug interactions.                                       of psychiatric illness, drug and alcohol abuse, and
         5. Provide counseling points to provide to patients about             cardiac morbidity, which can lead to an increase in
            therapy for insomnia.                                              overall utilization of health care resources.

            INTRODUCTION                                                       INSOMNIA DESCRIPTION
            insomnia is the most common sleep complaint among                  insomnia is a disorder characterized by any of the
            Americans. Poor sleep quality and quantity can impact              following symptoms: difficulty initiating sleep, dif-
            daytime functioning, and these effects extend beyond the           ficulty maintaining sleep, waking too early, or inability
            patient. Work and personal obligations may suffer when sleep       to achieve restorative sleep with associated func-
            is disrupted. According to the 2008 Sleep in America Poll,         tional impairment during the day. insomnia is classi-
            65 percent of the survey respondents reported having sleep         fied as primary (idiopathic) or secondary (comorbid).
            problems at least a few nights a week within the past month,       Primary insomnia is a diagnosis that is made after
                                              with 44 percent having           all other potential causes have been excluded.
Useful Web Sites                              problems every night or al-      Secondary insomnia is attributable to another medi-
                                              most every night. the most       cal condition or the adverse effects of medications.
■ www.aasmnet.org
                                              common complaints were           insomnia is further classified as acute or chronic
Web site for the American Academy of
                                              waking up unrefreshed (49        based on the duration of symptoms. Acute insomnia
Sleep Medicine. It contains patient-cen-
                                              percent), waking during the      generally lasts fewer than 30 days, and can usu-
tered information and provides links to
other sites for more information on sleep     night (42 percent), waking       ally be associated with an acute life stress or crisis,
and sleep disorders.                          up too early and being un-       environmental factors, acute illness, or medications.
■ www.sleepfoundation.org                     able to go back to sleep (29     chronic insomnia lasts for more than 30 days and
Web site for the National Sleep Founda-       percent), and difficulty fall-   is commonly associated with chronic medical and
tion. It contains patient-centered informa-   ing asleep (26 percent). in-     psychiatric conditions. Most patients will develop
tion regarding sleep topics along with        terestingly, only 15 percent     chronic intermittent insomnia, experiencing sleep
information about treatment options for       of the survey respondents        problems for several nights followed by a problem-
sleep disorders. The site also provides in-   reported having been diag-       free period before the symptoms return.
formation geared toward educating health      nosed with a sleep disorder           the prevalence of chronic insomnia has been
professionals about sleep disorders.
                                              by a physician. this is likely   reported to be higher in women and older adults.



         44   america’s   Pharmacist | September 2009                                                          www.americaspharmacist.net
                                                       table 1: international classification of Sleep Disorders
Alcohol abuse, nicotine use, and the use of
                                                       Diagnostic criteria
certain medications are also associated with
an increased prevalence of insomnia. other             A. A complaint of difficulty initiating sleep, difficulty maintaining
                                                          sleep, or waking up too early, or sleep that is chronically
risk factors identified include psychiatric illness,      nonrestorative or poor in quality
medical comorbidities, impaired social relation-       B. The above sleep difficulty occurs despite adequate opportunity
                                                          and circumstances to sleep
ships, chronic stress, lower socioeconomic
                                                       C. At least one of the following forms of daytime impairment related
status, separation from a spouse or significant           to the nighttime sleep difficulty is reported by the patient:
other, and unemployment.                                    1. Fatigue or malaise
                                                            2. Attention, concentration, or memory impairment
                                                            3. Social or vocational dysfunction or poor school
EVALUATION                                                     performance
                                                            4. Mood disturbance or irritability
there are several classification systems avail-
                                                            5. Daytime sleepiness
able to diagnose insomnia. Many clinicians                  6. Motivation, energy, or initiative reduction
use the international classification of Sleep               7. Proneness for errors/accidents at work or while driving
                                                            8. Tension, headaches, or gastrointestinal symptoms in
Disorders general criteria for insomnia to make                response to sleep loss
the diagnosis. (See table 1.) A comprehen-                  9. Concerns or worries about sleep
sive sleep history should be obtained before
insomnia can be diagnosed. this sleep his-
tory should cover specific insomnia complaints,          concentration and memory. this will often interfere with the
pre-sleep conditions, sleep-wake patterns, any           ability to perform daily activities, which may affect inter-
other sleep-related symptoms, and any daytime            personal relationships and work productivity. Many people
consequences. comorbid medical conditions                suffering from chronic insomnia will experience increased
and medication usage must be evaluated in                absenteeism from work, increased risk of psychiatric disor-
detail to identify any possible contributing fac-        ders, impaired cognition, and an overall negative quality of
tors. (See tables 2 and 3.) Physical examination         life. they have also been shown to have higher rates of drug
and laboratory testing are not necessary to make         and alcohol abuse and cardiac morbidity. People suffering
the diagnosis of insomnia. However, this type of         from sleep deprivation have been shown to be at an in-
evaluation should be performed to identify any           creased risk of driving accidents and decreased productivity
secondary causes for insomnia such as obstruc-           at work. According to the Sleep in America Poll, 32 percent of
tive sleep apnea and thyroid dysfunction.                all of the respondents reported that they have driven drowsy
     A thorough evaluation of the patient’s cur-         at least once per month. Among those, 36 percent stated that
rent symptoms, along with any reported daytime           they have fallen asleep while driving, and 2 percent of those
consequences due to lack of quality sleep, is            have had an accident or near accident while driving. When
necessary to determine if treatment is necessary.        asked about sleepiness at work, 29 percent of respondents
A sleep diary may also be a helpful tool when            stated that they have fallen asleep or become very sleepy at
evaluating insomnia symptoms. A one to two week          work. Sixty-five percent of those respondents reported having
sleep diary should include information regarding         experienced at least one of the following attributes at work
bedtime, total sleep time, time to sleep onset,          due to their sleepiness: impatience with others, boredom at
number of nighttime awakenings, daytime naps,            work, difficulty concentrating, lower than expected productiv-
use of medications, and the patient’s subjective         ity, lack of organization at work, avoidance of interactions with
feeling in the morning. Bed partner interviews, at       others, repeating job duties because of mistakes, and failure
home sleep logs, and self-administered question-         to complete assigned tasks.
naires may also provide beneficial information.
                                                         OVERVIEW OF MANAGEMENT
CONSEQUENCES OF INSOMNIA                                 goals of therapy for the management of insomnia are to
insomnia is usually associated with sleepiness,          improve sleep quality and quantity, to improve daytime func-
fatigue, mood disturbances, and difficulties with        tion, and to cause minimal adverse effects due to medica-



www.americaspharmacist.net                                                         September 2009 | america’s Pharmacist   45
 table 2: common causes for Secondary insomnia
                                                                  Stimulus Control Therapy
                                                                  Stimulus control therapy teaches patients to elimi-
     Alcohol Use
     Anxiety
                                                                  nate distractions from the bedroom and to associ-
     Chronic Obstructive Pulmonary Disease (COPD)                 ate the bedroom with only sleep and sex. Behav-
     Congestive Heart Failure (CHF)                               iors such as reading or television watching should
     Diabetes Mellitus
     Dementia                                                     be avoided in the bedroom. Stimulus control also
     Depression                                                   involves only going to bed when sleepy, leaving the
     Fibromyalgia
     Gastroesophageal Reflux Disease (GERD)
                                                                  bedroom if not asleep within 20 minutes, maintain-
     Hyperthyroidism                                              ing a regular wake-up schedule regardless of sleep
     Medications (See Table 3)                                    duration, and avoiding naps. this therapy is not
     Menopause
     Obstructive Sleep Apnea                                      recommended for patients with restricted mobility,
     Pain                                                         and/or those at increased risk for falls.
     Panic Disorder
     Pregnancy
     Restless Leg Syndrome                                        Sleep Restriction Therapy
     Seizure Disorder                                             Sleep restriction therapy requires setting limits on
     Stroke
     Urinary Incontinence                                         the time in bed with the goal of maximizing sleep
                                                                  efficiency. Patients are asked to keep sleep diaries
                                                                  in order to estimate their total sleep time and to
tions. Eliminating insomnia, unfortunately, is not usually the    then restrict their time in bed based on this time
endpoint goal. Appropriate management of any existing             frame. the time spent in bed must not be less
comorbidity may relieve the symptoms of insomnia. Howev-          than five hours and the morning wake time should
er, treatment strategies must be individualized for the patient   be consistent throughout the therapy. using this
despite the cause. non-pharmacological interventions are          method, patients should gradually be able to
recommended as initial therapy in the treatment of chronic        increase the amount of time that is spent in bed
insomnia. these treatments should be utilized prior to initiat-   because they are able to make bedtime earlier by
ing medication therapy. When pharmacotherapy becomes              15-minute increments as long as sleep efficiency
necessary, the choice of a specific agent should be based         (total sleep time divided by time spent in bed then
on the following: (1) symptoms present, (2) treatment goals,      multiplied by 100) is 90 percent or better. Sleep
(3) past treatment response, (4) patient preference, (5)          restriction therapy should be avoided in patients
cost, (6) medication availability, (7) comorbid conditions, (8)   with epilepsy, bipolar disorder, or sleepwalking
medication interactions, and (9) side effects. Food and Drug      problems because this therapy may worsen these
Administration (FDA)-approved pharmacotherapy options             disorders. Also, patients should be warned that this
are provided in table 4.                                          therapy might result in increased daytime sleepi-
                                                                  ness and make activities requiring high cognitive
Non-pharmacological Therapies                                     functioning unsafe.
Sleep Hygiene Education
Sleep hygiene education teaches patients behaviors that           Cognitive Behavior Therapy
will improve sleep quality. good sleep hygiene behaviors          cognitive behavior therapy is instituted to cor-
include avoiding caffeine, alcohol, and nicotine, maintaining     rect some of the misconceptions about sleep.
regular exercise, avoiding heavy exercise within two hours        this form of therapy focuses on identifying,
of bedtime, maintaining a regular sleep-wake cycle, avoid-        challenging, then replacing the attitudes regard-
ing naps, and maintaining a dark bedroom. these types of          ing sleep and the effect of sleep loss. Examples
behaviors promoted for patient use should be customized           of concepts reviewed with patients include the
based on the specific needs of the patient. Regardless            reinforcing that patients require seven to eight
of the cause of insomnia, most patients can benefit from          hours of sleep per night, discussing the normal
behaviors to improve sleep habits.                                changes in sleep associated with aging, and



46    america’s   Pharmacist | September 2009                                                  www.americaspharmacist.net
easing exaggerated concerns about the impact                substances, so there is a potential for addiction and physical
of insomnia. these techniques are believed to               dependence. therefore, therapy with these agents should be
be the standard of care when combined with                  tapered off gradually to avoid withdrawal symptoms, especially
sleep restriction therapy and stimulus control.             after sustained use (use more than 10 days).
                                                                Benzodiazepines (except temazepam) are substrates
Relaxation Therapy                                          of cYP 3A4. inhibitors of this system, such as Azole
Relaxation therapy is most beneficial for pa-               antifungals, Macrolide antibiotics, and grapefruit juice can
tients with high muscular tension and cognitive             increase benzodiazepine toxicity. inducers of this system,
arousal throughout the day and night. Several               such as carbamazepine and St. John’s Wort, can decrease
techniques are employed in order to deacti-                 their effectiveness. Alcohol and other central nervous sys-
vate this hyperactivity. Examples of relaxation             tem depressants can increase the risk of the cnS depres-
techniques include imagery training, meditation,            sion seen with benzodiazepines. Benzodiazepines should
and progressive muscle relaxation. Patients                 be used with caution in patients with sleep apnea, depres-
can perform most of these therapies after initial           sion, psychosis, respiratory disease, and hepatic or renal
professional training and regular practice.                 impairment. Benzodiazepines therapy is contraindicated in
                                                            pregnant patients (pregnancy category X) and patients with
Pharmacological Therapies                                   narrow angle glaucoma.
Benzodiazepines
Benzodiazepines have historically been the first line        table 3: Medications causing Secondary insomnia
agents used for the treatment of insomnia, but they           Albuterol
have lost favor due to their side effect profile and          Antidepressants (Selective Serotonin Reuptake inhibitors, Serotonin
                                                                 norepinephrine Reuptake inhibitors, Monoamine oxidase inhibitors)
problems with dependence and tolerability. these              Beta-blockers
agents work by enhancing the inhibitory effect of (-          caffeine
aminobutyric acid-A (gABA-A) on neuronal excitabil-           corticosteroids
                                                              Decongestants (phenylephrine, pseudoephedrine)
ity, resulting in cnS depression. they are effective          Diuretics
for decreasing the time to sleep onset and prolong-           HMg-coA Reductase inhibitors
                                                              narcotic Analgesics
ing sleep duration. However, it has been shown                nicotine
that their efficacy declines when used for more               Stimulants (methylphenidate, amphetamine derivatives, cocaine)
than 30 days. the only benzodiazepines FDA ap-                theophylline

proved for the short-term treatment of insomnia are
ProSom (estazolam), Dalmane (flurazepam), Doral             Non-Benzodiazepine Hypnotic
(quazepam), Restoril (temazepam), and Halcion               the newer non-benzodiazepine hypnotics, Ambien (zolpidem),
(triazolam). there is little difference in the effective-   Sonata (zaleplon), and Lunesta (eszopiclone), have become
ness of these agents, so no one drug is considered          widely used as alternatives to benzodiazepine therapy. these
preferable to the others. the primary considerations        agents interact with the benzodiazepine gABA-A receptor in a
in choosing an agent are the onset of action and the        similar manner as benzodiazepines, but these molecules are
half-life. the potential side effects of this drug class    structurally different. non-benzodiazepine gABA-A receptor
include impaired daytime performance, rebound               agonists have been marketed as having a better safety profile
insomnia, rebound anxiety (triazolam) dizziness,            than the older benzodiazepine agents. Specifically, they have
and impaired memory. there is also data showing             been touted as causing less rebound insomnia and having
an increased risk of falls and hip fractures in elderly     less potential for abuse. However, like the benzodiazepines,
patients treated with benzodiazepines. Agents               they are schedule iV controlled substances and have been
with longer half-lives will have an increased risk of       associated with causing withdrawal symptoms, physical
affecting daytime performance and causing dizzi-            dependence, and tolerance resulting in the potential for abuse,
ness when compared to those with shorter half-              especially after chronic therapy. the longer acting agents may
lives. All of these agents are schedule iV controlled       also cause daytime performance impairment.



www.americaspharmacist.net                                                              September 2009 | america’s Pharmacist        47
 table 4: FDA-Approved Pharmacotherapy options
     Drug                Recommended        Onset (Hr)   Half-life (Hr)     Notes
                         Dose
     Benzodiazepines
     Estazolam           0.5–2 mg           1            10–24              • Short-term use only
                                                                            • can be drug of choice for elderly when therapy is
                                                                              indicated due to lack of active metabolites
     Flurazepam          15–30 mg           0.25–0.3     2–113              • Short-term use only
                                                                            • Avoid in elderly due to production of long-acting
                                                                              metabolite
     Quazepam            7.5–15 mg          2            73                 • Short-term use only
                                                                            • Avoid in elderly due to production of long-acting
                                                                              metabolite
     temazepam           15–30 mg           2–3          10–12              • Short-term use only
                                                                            • can be drug of choice for elderly when therapy is
                                                                              indicated due to lack of active metabolites
     triazolam           0.125–0.5 mg       0.25–0.5     2–6                • Short-term use only
                                                                            • take while in bed due to rapid onset
                                                                            • Avoid in elderly due to high incidence of cnS
                                                                              adverse effects
                                                                            • can cause rebound anxiety
     Non-benzodiazepine GABA-A Receptor Agonists
     Zolpidem            5–10 mg            0.5          3                  • Short-term use only
                                                                            • can be drug of choice in elderly if therapy is
                                                                              indicated
                                                                            • take immediately before bedtime if patient can
                                                                              devote 7–8 hours to sleep
     Zolpidem cR         6.25–12.5 mg       0.5          3                  • can be used long-term if indicated
                                                                            • take immediately before bedtime if patient can
                                                                              devote 7–8 hours to sleep
     Zaleplon            5–20 mg            Rapid        1                  • Short-term use only (7–10 days)
                                                                            • take immediately before bedtime
                                                                            • Dose can be repeated if necessary
     Eszopiclone         1–3 mg             Rapid        6                  • can be used long-term if indicated
                                                                            • take immediately before bedtime if patient can
                                                                              devote 8 hours to sleep
     Melatonin Receptor Agonists
     Ramelteon           8 mg               0.5          1–3                • can be used long-term if indicated
                                                                            • take within 30 min of bedtime
     Barbiturates
     Secobarbital        100–200 mg         0.25–0.5     15–40              • Short-term use only
                                                                            • Avoid in elderly due to long half-life and addictive
                                                                              potential




     All of these agents work to decrease the time to sleep on-           onset. An extended release formulation is approved
set, and the major difference between agents is their duration            for the treatment of insomnia due to difficulty with
of action. Zolpidem and eszopiclone have longer half-lives,               sleep onset with difficulty with sleep maintenance.
so these agents are useful for sleep maintenance in addition              this formulation is allowed for long-term use, and
to improving sleep onset problems. they also should only be               can be prescribed for more than 30 days. Eszopi-
taken when there is time for a full night’s sleep (seven to eight         clone is approved for the treatment of insomnia
hours). Zolpidem is approved for the short-term treatment of              and its use is also approved for more than 30 days.
insomnia where the primary complaint is difficulty with sleep             Zaleplon is FDA approved for the short-term (seven



48     america’s    Pharmacist | September 2009                                                              www.americaspharmacist.net
 table 4: FDA-Approved Pharmacotherapy options—Continued
  Drug                Recommended       Onset (Hr)        Half-life (Hr)   Notes
                      Dose
  Antihistamines
  Diphenhydramine     50 mg             1–3               2–10             • Short-term use only for infrequent insomnia
                                                                           • Associated with significant sedative and
                                                                             anticholinergic properties
                                                                           • Avoid in elderly


  Doxylamine          25 mg             0.5               10–12            • Short-term use only for infrequent insomnia
                                                                           • Associated with significant sedative and
                                                                             anticholinergic properties
                                                                           • Avoid in elderly


to 10 days) treatment of insomnia, but it has been            ing properties by helping to maintain the circadian rhythm to
shown to be effective for up to five weeks in clinical        support the normal sleep-wake cycle. this agent does not
trials. Zaleplon has a rapid onset of action and a            have any effect on gABA receptors or receptors that bind
short half-life, so it is very beneficial for patients with   neuropeptides, cytokines, serotonin, dopamine, noradrena-
problems going to sleep without causing issues                line, acetylcholine, or opiates. clinically, this contributes to
such as daytime drowsiness. However, it is not use-           the lack of dependence, tolerance, withdrawal symptoms,
ful for increasing sleep time or decreasing the num-          motor and cognitive deficits, and rebound insomnia noted
ber of awakenings at night. the main advantage                with ramelteon. the most common side effects associated
of this agent is that it can be taken in the middle of        with this agent include somnolence, dizziness, fatigue, head-
the night if the patient wakes up at least four hours         ache, nausea, and exacerbated insomnia.
before planning to rise.                                           Ramelteon is a major substrate of cYP1A2 and a mi-
     these agents are all substrates of cYP3A4                nor substrate of cYP2c9 and cYP3A4. concurrent use
to some extent. therefore, usage with potent                  of strong cYP1A2 inhibitors (such as fluvoxamine) may
cYP3A4 inhibitors can increase toxicity, while                result in increased serum concentrations of ramelteon;
cYP3A4 inducers may decrease effectiveness.                   therefore, they should not be used together. Medica-
Alcohol and other cnS depressants should be                   tions that inhibit cYP3A4 or cYP2c9 can also increase
avoided due to the added risk of cnS depres-                  the risk of toxicity, while those that induce these systems
sion. the non-benzodiazepine gABA-A receptor                  may diminish the effect of ramelteon. Patients should be
agonists should be used with caution in patients              instructed not to take ramelteon with or immediately after
with sleep apnea, respiratory disease, and severe             any high-fat meals or snacks, as this causes a delay in
hepatic dysfunction. All of these agents have a               absorption and beneficial effects. Because of the rapid
pregnancy category rating of c so they should not             onset of action, ramelteon should be taken immediately
be used in pregnant patients unless the benefits              before bedtime or while in bed. this agent should be
clearly outweigh the potential risk to the fetus.             used with caution in patients with moderate hepatic
                                                              impairment, and it should be avoided in severe hepatic
Melatonin Receptor Agonists                                   impairment. Dosage adjustments are unnecessary for
Rozerem (ramelteon) is the only FDA approved                  elderly patients or those with renal impairment. Ramelt-
therapy for insomnia that available by prescrip-              eon has a pregnancy category rating of c and is not
tion only and is not a controlled substance. it is            recommended for use in pregnant patients unless the
indicated for the treatment of insomnia charac-               benefits of therapy justify the potential risk to the fetus.
terized by difficulty with sleep onset. Ramelteon
is a melatonin receptor agonist with high affinity            Barbiturates
for melatonin Mt1 and Mt2 receptors. Activity at              Barbiturates are not currently recommended for the treat-
these receptors is believed to have sleep promot-             ment of insomnia because there are several disadvantages



www.americaspharmacist.net                                                              September 2009 | america’s Pharmacist   49
to their use: a narrow therapeutic index, lethal in case of an       Melatonin supplementation taken in the afternoon
overdose, quick tolerance development, high abuse poten-             or early evening has been shown to promote sleep,
tial, and many drug interactions. Amytal (amobarbital) and           but it has little effect if taken at bedtime. However, it
Seconal (secobarbital) are the only barbiturates that are            may be of some benefit to patients with sleep prob-
FDA approved for the short-term treatment of insomnia.               lems due to jet lag or shift work. Valerian root may
However, these agents should not be recommended as                   improve the quality of sleep, but its effectiveness is
therapy options. these agents are schedule ii controlled             not established. therefore, this agent is not recom-
substances and have a pregnancy category rating of D.                mended as therapy. Melatonin and valerian use is
                                                                     generally discouraged due to issues with standard-
Non-FDA Approved Agents: Antidepressants and                         ization of ingredients and dose variability due to the
Antipsychotics                                                       lack of FDA regulation.
the most commonly prescribed antidepressants for the
treatment of insomnia are Desyrel (trazodone), Remeron               FDA Warnings for Pharmacological Treatment
(mirtazapine), Elavil (amitriptyline), and Sinequan (doxepin).       in March 2007, the FDA requested labeling changes
these agents do not have an indication for insomnia, and             for several medications used in the treatment of in-
there is no real evidence supporting their use for insomnia          somnia. the agents included in this request were as
that is not associated with depression. trazodone is the most        follows: Ambien/Ambien cR (zolpidem), Butisol (bu-
commonly prescribed antidepressant, and it continues to be           tabarbital), carbrital (pentobarbital and carbromal),
one of the most frequently prescribed agents for the treat-          Dalmane (flurazepam), Doral (quazepam), Halcion
ment of insomnia. these agents are most valuable in patients         (triazolam), Lunesta (eszopiclone), Placidyl (ethchor-
with comorbid depression suffering from chronic insomnia.            vynol), Prosom (estazolam), Restoril (temazepam),
    Antipsychotic agents such as Seroquel (quetiap-                  Rozerem (ramelteon), Seconal (secobarbital), and
ine) have been used for insomnia, but there is no data               Sonata (zaleplon). the revised product labels in-
supporting this indication unless there is an associated             clude warnings about severe allergic reactions, such
psychiatric disorder.                                                as anaphylaxis and angioedema. Also included
                                                                     in the warning are complex sleep behaviors, such
Non-prescription Agents                                              as sleep-driving, making and eating food, sleep-
Benadryl (diphenhydramine) and unisom (doxylamine) are               walking, having sex and making phone calls while
first generation histamine (H1) antagonists approved as over         sleeping. the patient may have little or no memory
the counter sleep aids for the short-term treatment of insom-        of these activities because they are not fully awake.
nia. use of first generation antihistamines should be limited to     All of these agents are considered to have these
those with infrequent symptoms of insomnia. these agents             risks, but there may be differences in the frequency
are not recommended for chronic insomnia due to tolerance            of these risks depending on the agent.
issues and lack of efficacy and safety data. caution should be
used when recommending these agents to patients with co-             Combination Therapy
morbid conditions, such as glaucoma BPH, or patients at risk         the data showing that the combination of be-
of falling, such as the elderly. these agents have a pregnancy       havioral therapy and medication therapy is more
category rating of B, so they may be cautiously used in preg-        effective than behavioral therapy alone is limited.
nant patients. common side effects include anticholinergic           Most of the data supports the use of behavior
side effects (orthostatic hypotension magnifying the risk of falls   therapy alone over medication therapy, especially
for the elderly), daytime sedation, and cognitive impairment.        for the treatment of chronic insomnia. there has
      Melatonin and valerian root are both commercially mar-         been evidence to show a clear advantage or
keted herbal products used as sleep agents. Endogenous               disadvantage to using combination therapy. in
melatonin is a hormone produced by the pineal gland. its re-         general, combination therapy is reserved for those
lease normally rises in the evening and falls during the morning     patients achieving inadequate results after contin-
hours. Peak values are associated with maximum sleep quality.        ued non-pharmacological therapy modifications.



50   america’s   Pharmacist | September 2009                                                          www.americaspharmacist.net
CONCLUSION                                              with the ability to sleep, such as irregular sleep schedule,
Psychological and behavior interventions are            exercise before bed, alcohol, caffeine, and nicotine.
considered to be effective and are recommended              When counseling patients, it should be explained
as first line treatment of chronic insomnia. Stimulus   that medications are only effective for a short time frame
control therapy, relaxation therapy, and cognitive      and overuse can actually make the insomnia worsen.
behavior therapy are recommended as standard of         Pharmacists should review some of the common and
care and should be implemented for most patients.       unique side effects associated with their insomnia
When initial therapy has been ineffective, pharmaco-    prescription therapy. Also, pharmacists are in the unique
therapy may be considered. Short-acting benzodi-        position to help educate patients regarding the appropri-
azepines or non-benzodiazepine gABA-A receptor          ateness of therapy with non-prescription agents.
agonists are recommended as first line agents. tri-
azolam and zaleplon are best indicated for patients
with sleep onset due to their short onset of action     Ariane Conrad, PharmD, is assistant professor of clinical pharmacy at
and half-life. Quazepam, zolpidem, and eszopiclone      the Xavier University of Louisiana College of Pharmacy in New Orleans.

are better for patients with problems with sleep
maintenance due to their longer half-life. the lowest
effective dosage should be used to minimize issues        Editor’s	Note: to obtain the complete list of references used
                                                          in the article, contact chris Linville at ncPA (703-838-2680)
with side effects, especially in elderly patients.
                                                          or at chris.linville@ncpanet.org.
     Benzodiazepines and non-benzodiazepine
gABA-A receptor agonists may need to be
avoided in patients with a history of drug or alcohol
abuse, as these agents have the potential for
abuse. Ramelteon may be considered first for in-           CONTINUING EDUCATION QUIZ
somnia in the elderly and in patients with a history       	 Select	the	correct	answer.
of drug abuse. other sedating medications, such
as antidepressants and antipsychotic agents, are           1. Which of the following is not a risk factor for the
only recommended when used to treat a concomi-             development of insomnia?
tant illness. non-prescription antihistamines, herbal      a. tobacco use
agents and barbiturates are generally not recom-           b. Age under 30 years
mended due to safety and efficacy concerns. the            c. Female sex
FDA recommends that pharmacotherapy use for                d. Psychiatric illness
insomnia is limited to one month. Longer use (up
to one year) may be considered if the patient is not       2. Which of the following is not a goal of therapy for the
experiencing any side effects from therapy.                management of insomnia?
                                                           a. improve daytime function
PATIENT COUNSELING                                         b. improve sleep quality
For any therapy to be successful, the patient              c. Reduce adverse effects associated with therapy
must be properly educated regarding the therapy            d. Eliminate insomnia
options available. Patients should be educated
regarding the advantages and disadvantages                 3. Which of the following factors should be considered
associated with the non-pharmacological and                when choosing therapy for the treatment of chronic
pharmacological therapies. Furthermore, they               insomnia?
should be involved in the decision making process          a. Patient preference
which will facilitate effectiveness and compliance.        b. Presenting symptoms
Patients should also be encouraged to avoid some           c. comorbidities
of the behaviors and substances that may interfere         d. All of the above


www.americaspharmacist.net                                                         September 2009 | america’s Pharmacist   51
4. Which non-pharmacological therapies is considered            10. Which of the following non-pharmacological
standard care for the treatment of insomnia?                    therapies is not appropriate for patients
a. cognitive behavior therapy                                   diagnosed with epilepsy?
b. Sleep hygiene therapy                                        a. Relaxation therapy
c. Sleep restriction therapy                                    b. Sleep restriction
d. All of the above                                             c. Sleep hygiene
                                                                d. Stimulus control
5. Which of the following drugs is not recommended for the
management of insomnia in elderly patients?                     11. Which of the following patient
a. temazepam                                                    characteristics would be a contraindication for
b. Estazolam                                                    therapy with benzodiazepines?
c. Flurazepam                                                   a. Age more than 65 years
d. All of the above                                             b. chronic renal insufficiency
                                                                c. Pregnancy
6. Which of the following medications has been associated       d. Severe hepatic dysfunction
with causing high rates of rebound anxiety?
a. triazolam                                                    12. Which of the following benzodiazepines
b. Zolpidem                                                     is considered an appropriate choice for
c. Diphenhydramine                                              insomnia therapy for an elderly patient when a
d. Ramelteon                                                    benzodiazepine is desired?
                                                                a. triazolam
7. JM is a 40-year-old female taking quazepam for the           b. Estazolam
treatment of her insomnia. Which of the following antibiotics   c. Lorazepam
should not be prescribed for this patient?                      d. Diazepam
a. ciprofloxacin
b. Fluconazole                                                  13. Which of the following patient
c. Penicillin                                                   characteristics would be a contraindication for
d. Sulfamethoxazole/trimethoprim                                therapy with ramelteon?
                                                                a. Age more than 65 years
8. All of the following medications are Food and Drug           b. chronic renal insufficiency
Administration approved for the treatment of insomnia           c. Pregnancy
EXcEPt:                                                         d. Severe hepatic dysfunction
a. trazodone
b. Ramelteon                                                    14. Which of the following medications is
c. triazolam                                                    considered to be a secondary cause of
d. Eszopiclone                                                  insomnia?
                                                                a. Acetaminophen
9. Which of the following insomnia symptoms is most likely      b. Ramipril
to respond to therapy with zaleplon?                            c. Decongestants
a. Waking too early                                             d. carbamazepine
b. Difficulty initiating sleep
c. Difficulty maintaining sleep                                 15. Each of the following is considered to be a
d. All of the above                                             medical cause for insomnia except:
                                                                a. chronic obstructive pulmonary disease (coPD)
                                                                b. Allergic rhinitis
                                                                c. Diabetes
                                                                d. obstructive sleep apnea


52   america’s   Pharmacist | September 2009                                               www.americaspharmacist.net
16. Which of the following insomnia symptoms        Management of Insomnia
is most likely to respond to therapy with           Sept. 1, 2009 (expires Sept. 1, 2012)

flurazepam?
                                                      FREE ONLINE C.E. Pharmacists now have online access to ncPA’s
a. Waking too early                                   c.E. programs through Powered by cEcity. By taking this test on-
b. Difficulty initiating sleep                        line—go to the continuing Education section of the ncPA Web site
                                                      (www.ncpanet.org) by clicking on “Professional Development” under
c. Difficulty maintaining sleep                       the Education heading you will receive immediate online test results
                                                      and certificates of completion at no charge.
d. All of the above
                                                    To earn continuing education credit: ACPE Program 207-000-09-009-H01-P
17. Which of the following statements regarding     A score of 70 percent is required to successfully complete the c.E. quiz.
antidepressant use for insomnia therapy is tRuE?    if a passing score is not achieved, one free reexamination is permitted.
a. Antidepressants have been proven to be ef-       Statements of credit for mail-in exams will be available online for you
                                                    to print out approximately three weeks after the date of the program
   fective therapy options for insomnia.
                                                    (transcript Web site: www.cecerts.oRg). if you do not have access to a
b. Antidepressants are approved for short-term      computer, check this box and we will make other arrangements to send
   treatment of insomnia.                           you a statement of credit: q
c. Antidepressants are only appropriate for use     Record your quiz answers and the following information on this form.
   in patients with comorbid depression and         q      ncPA Member                                      License
                                                           ncPA Member no. ____________________             State __________ no. _____________________
   insomnia.                                        q      nonmember                                        State __________ no. _____________________
d. Antidepressants should be recommended as
                                                    All fields below are required. Mail this form and $7 for manual processing to:
   first line therapy for chronic insomnia.         ncPA c.E. Processing ctr.; 405 glenn Drive, Suite 4; Sterling, VA. 20164
                                                    _____________________________________________________________________________________
                                                    Last 4 digits of SSn                                            MM-DD of birth
18. AJ is a 70-year-old patient presenting to the   _____________________________________________________________________________________
                                                    name
pharmacy complaining of insomnia symptoms           _____________________________________________________________________________________
lasting for seven days. He has a history of         Pharmacy name
                                                    _____________________________________________________________________________________
hypertension and diabetes. Which of the             Address
                                                    _____________________________________________________________________________________
following would be appropriate to recommend         city                                                             State             ZiP
                                                    _____________________________________________________________________________________
for this patient?                                   Phone number (store or home)

a. Doxylamine                                       _____________________________________________________________________________________
                                                    Store e-mail (if avail.)                                         Date quiz taken
b. Diphenhydramine
                                                    Quiz: Shade in your choice
c. Valerian root                                              a         b      c      d       e                       a      b         c     d      e
d. none of the above                                  1.      q        q       q     q       q               11.    q        q         q     q     q
                                                      2.      q        q       q     q       q               12.    q        q         q     q     q
                                                      3.      q        q       q     q       q               13.    q        q         q     q     q
19. Which of the following medications does           4.      q        q       q     q       q               14.    q        q         q     q     q
not have a FDA-mandated warning attached to           5.      q        q       q     q       q               15.    q        q         q     q     q
its labeling?                                        6.       q        q       q     q       q               16.    q        q         q     q     q
a. Zolpidem                                          7.       q        q       q     q       q               17.    q        q         q     q     q
b. Secobarbital                                      8.       q        q       q     q       q               18.    q        q         q     q     q
                                                     9.       q        q       q     q       q               19.    q        q         q     q     q
c. Doxylamine                                       10.       q        q       q     q       q               20.    q        q         q     q     q
d. triazolam
                                                    Quiz: Circle your choice
                                                    21. is this program used to meet your mandatory c.E. requirements?
20. Each of the following medications must be           a. yes b. no
taken immediately before bedtime due to their       22. type of pharmacist: a. owner b. manager c. employee
rapid onset of action EXcEPt:                       23. Age group: a. 21–30 b. 31–40 c. 41–50 d. 51–60 e. over 60

a. triazolam                                        24. Did this article achieve its stated objectives? a. yes b. no
                                                    25. How much of this program can you apply in practice?
b. temazepam                                            a. all b. some c. very little d. none
c. Ramelteon
                                                    How long did it take you to complete both the reading and the quiz? ______ minutes
d. Zaleplon


                                                                   NCPA®	is	accredited	by	the	Accreditation	Council	for	Pharmacy	Education	as	a	provider	
                                                                   of	continuing	pharmacy	education.	NCPA	has	assigned	two	contact	hours	(0.2	CEU)	
                                                                   of	continuing	education	credit	to	this	article.	Eligibility	to	receive	continuing	education	
www.americaspharmacist.net                                                                       May 2007 | america’s Pharmacist 53
                                                                   credit	for	this	article	expires	three	years	from	the	month	published.

								
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