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Treatment of Insomnia in Anxiety Disorders
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Treatment of Insomnia in Anxiety Disorders
January 05, 2012 | Sleep Disorders [1], Anxiety [2], ADHD [3], Comorbidity In Psychiatry [4],
Generalized Anxiety [5], Major Depressive Disorder [6], Addiction [7], Alcohol Abuse [8]
By Gregory M. Asnis, MD [9], Elishka Caneva, MD [10], and Margaret A. Henderson, MD [11]
How often do insomnia and anxiety disorders coexist? And how best to treat patients with comorbid
insomnia and anxiety? Answers here..
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Insomnia is highly prevalent in psychiatric disorders, and it has
significant implications. This review focuses on insomnia in the context of anxiety disorders. The
prevalence of comorbid insomnia in anxiety disorders is addressed and the clinical implications
associated with insomnia are discussed as well as when and how to treat this important comorbidity.
Just how specifically insomnia relates to and possibly affects anxiety disorders is highlighted by the
fact that insomnia is one of the defining criteria in a number of the DSM-IV-TR anxiety disorders. For
example, difficulty in falling or staying asleep is a criterion for PTSD, acute stress disorder, and
generalized anxiety disorder (GAD).
The relationship of insomnia to anxiety disorders is also influenced by comorbid major depression.
The severity of insomnia is increased when an anxiety disorder is comorbid with a major depressive
disorder (MDD).1 This is highly relevant because 58% of MDD patients have a lifetime anxiety
disorder.2
The presence of insomnia has a deleterious effect on daytime functioning and negative effects on
quality of life, including social and work relationships.3 Also, there is clear evidence that the presence
of insomnia in anxiety disorders is associated with increased morbidity. For example, in patients with
PTSD, insomnia is associated with an increased likelihood of suicidal behavior, depression, and
substance abuse as well as nonresponsiveness to treatment.4-6 In addition, insomnia as an early
symptom in traumatized patients increases the risk of the development of PTSD 1 year later.7
Early assessment
It is important to carefully assess for insomnia early in the evaluation of patients with anxiety
disorders and to aggressively treat this complicating comorbidity. Insomnia is an underrecognized
and undertreated problem. Patients rarely report their symptoms of insomnia spontaneously to their
doctor. Adding to the problem of detecting insomnia is the finding that doctors rarely inquire about
insomnia in their patients.3,8,9 Thus, a carefully taken history is an important first step in the
assessment of insomnia.
Self-rating sleep questionnaires and direct clinical interviews are used to obtain a history of potential
sleep disorders (eg, insomnia). A number of well-validated sleep questionnaires have been widely
used. The most widely used and validated questionnaire is the 19-question Pittsburg Sleep Quality
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Index. The questions cover sleep quality, sleep problems, sleep medications, and so on, within the
past month.10 Another widely used questionnaire is the Leeds Sleep Evaluation Questionnaire
(LSEQ). The LSEQ consists of 10 self-rating questions that cover sleep and aberrant sleep
behaviors.11
Besides self-rating questionnaires that depend on memory of sleep disturbances, a sleep log or diary
can confirm questionable sleep disturbances prospectively. The use of a sleep log allows for an
analysis of day-to-day sleep patterns, such as the time that the patient went to bed, sleep latency,
and nighttime awakenings.8,9 The log is filled out by the patient shortly after awakening in the
morning (see Morin9(p38) for an example of a sleep log). If at all possible, monitoring for up to 2 weeks
is highly recommended because it allows for sleep abnormalities that might show marked day-to-day
variability and would more likely be detected by extensive monitoring.12,13
What is already known about insomnia
in patients with anxiety disorder?
? Anxiety disorders frequently coexist with insomnia. The latter is believed
to be part and parcel of various anxiety disorders and is one of the
defining criteria of a number of them.
What new information does this article provide?
? Our article clarifies new approaches to considering insomnia in anxiety
disorders. The presence of insomnia should be considered a comorbid
illness and treated on its own. Pharmacotherapy, cognitive-behavioral
therapy, and a combination of both are discussed. Insomnia is an added
pathology that brings increased morbidity to patients with anxiety
disorders. Our review suggests that successful treatment of insomnia
actually increases the responsiveness of anxiety disorders to many
antianxiety treatments.
What are the implications for psychiatric practice?
? When evaluating patients with anxiety disorders, psychiatrists should
carefully evaluate for the presence of insomnia. Patients infrequently
bring up this symptom on their own. If insomnia is present, aggressive
treatment early in the course of therapy is highly suggested.
If the presence of insomnia is suspected, interviewing a spouse, a significant other, or a caregiver is
helpful. Some patients who believe they have insomnia symptoms appear to have “sleep state
misperception,” where their partners clearly state that their sleep is normal.14 These “others” can
also report problems that are likely not obvious to the patient:
• Apnea spells or excessive snoring as seen in obstructive apnea
• Excessive body movements as seen in periodic leg movement disorder and restless legs syndrome
• Various sleep-related behaviors (sometimes violent and aggressive) as seen in rapid eye
movement behavior disorder (RBD)
• Sleepwalking
Referral to a sleep specialist and sleep polysomnography has been recommended if pharmacological
or nonpharmacological options are not working. Referral is also warranted for patients with insomnia
in whom a specific sleep disorder, such as obstructive sleep apnea, periodic limb movements,
narcolepsy, or RBD, is suspected.12,15 Even when a visit to a sleep laboratory is suggested, the cost
of an overnight visit is often prohibitive—more than $1000 per night; usually 2 nights are required
with the first being an adaptation night for the patient. Insurance frequently does not cover these
costs.16 If it is found that the patient has sleep apnea, a sleep movement disorder, RBD, or a number
of other sleep disorders, specific nonhypnotic treatments may be required (eg, continuous positive
airway pressure for sleep apnea is the treatment of choice).
Before beginning treatment of anxiety disorder–associated insomnia symptoms, rule out any
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concurrent medical illness, medication treatment, or substance use that might be inducing or
worsening insomnia. Many medical illnesses, such as cardiovascular disorders (eg, congestive heart
failure), pulmonary disorders (eg, emphysema), endocrinopathies (eg, thyroid disorders), GI
disorders (eg, acid reflux), and neurological disorders (eg, pain syndromes), are associated with
insomnia.12
Carefully assess the use of medications for medical and psychiatric disorders that may be implicated
in insomnia as well as caffeine or alcohol use. Even small amounts of the latter have been associated
with increased nighttime awakenings.
One should be highly suspicious of alcohol or substance use or abuse in patients with anxiety
disorders because these are frequently comorbid.4 Various medications are associated with
insomnia, including psychostimulants (eg, ephedrine found in cold medication, amphetamines used
in ADHD), bronchodilators (eg, theophylline, albuterol), pain medication (eg, oxycodone), and
antidepressants (eg, SSRIs).12 The latter category is particularly important because many
antidepressants are FDA-approved and are prescribed for anxiety disorders.
Before providing any significant intervention for insomnia, a careful evaluation regarding behaviors
that might contribute to insomnia should be made. Daytime naps, late nighttime snacks or meals,
watching television in bed, nighttime exercise, or excessive light or loudness in the bedroom should
be identified and modified. Eliminating these behaviors can lead to significant sleep improvements. A
13-item self-rating questionnaire by Mastin and colleagues17 can help elicit sleep hygiene
information.
Pharmacological options
The treatment of insomnia in patients with anxiety disorders is, for the most part, the same as the
treatment of insomnia per se: pharmacological, nonpharmacological, or a combination of the two.
The primary treatment of insomnia is pharmacological because of the rapid onset of action (eg,
hypnotics are usually effective within days to 1 week of use). The most common
nonpharmacotherapy, cognitive-behavioral therapy for insomnia (CBT-I) takes considerably
longer.3,8,12 Currently, the FDA has 11 approved drugs for the treatment of insomnia:
• Nonbenzodiazepines: eszopiclone, zolpidem, zolpidem ER, and zaleplon
• Benzodiazepines: estazolam, flurazepam, quazepam, temazepam, and triazolam
• A tricylic antidepressant: low-dose sinequan
• A melatonin agonist: ramelteon
In recent years, nonbenzodiazepines have become the most recommended of the approved
hypnotics. (There has been less and less reliance on benzodiazepines.) Not only are
nonbenzodiazepines effective in treating insomnia (equivalent to the benzodiazepines), but there is a
notion that they are safer than benzodiazepines.3,12
Both nonbenzodiazepines and benzodiazepines are associated with adverse effects that include
fatigue, dizziness, ataxia, and the development of dependence and tolerance with long-term use.
Although head-to-head studies comparing these classes of hypnotics have been minimal, a recent
meta-analysis supports the finding of reduced adverse effects for the nonbenzodiazepines.18 The
nonbenzodiazepines typically have a shorter half-life and are more selective at the γ-aminobutyric
acid receptor, factors that are partially responsible for less residual daytime sedation and other
adverse effects.
In the treatment of anxiety disorders with comorbid insomnia, the latter should be treated
concurrently with, but independently of, the anxiety disorder per se. The idea that one should wait to
see whether the insomnia resolves with only the treatment of the anxiety disorder is no longer valid.
Clinical experience has shown that without targeted insomnia treatment, insomnia frequently
persists.3,19
When adding a hypnotic to an antidepressant in the treatment of anxiety, the risk to benefit ratio
must be considered. Pollack and colleagues20 looked at a large group of patients with GAD comorbid
with insomnia (N = 595). The patients received either 10 mg of escitalopram coadministered with 3
mg of eszopiclone or the escitalopram with placebo. Those in the active hypnotic treatment group
had a significant response in their insomnia by the first week. The combination of medications was
well tolerated with no significant increase in adverse effects.
Most surprisingly, the anxiety scores for those patients who received the hypnotic significantly
improved starting at week 4 even after removing insomnia symptoms from the anxiety assessment.
The time to onset of the anxiolytic response was also reduced. In addition, the combination
treatment led to a slightly better symptom response and remission rate for the anxiety disorder.
Similar results were reported in a 12-week open-label study (N = 27) undertaken by Gross and
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colleagues.21 The researchers evaluated ramelteon (8 mg/d), a melatonin agonist, in patients who
had GAD comorbid with insomnia and whose condition was partially responsive to an SSRI or a
serotonin norepinephrine reuptake inhibitor. The hypnotic was well tolerated, effective for insomnia,
and appeared to facilitate the treatment of GAD.
A double-blind placebo-controlled study by Fava and colleagues22 evaluated the efficacy and safety
of zolpidem extended-release (12.5 mg/d) versus placebo in patients with comorbid GAD and
insomnia who were being treated with escitalopram (10 mg/d). Sleep measures improved
significantly by the end of week 1, and there was no added burden of adverse effects. Zolpidem did
not show a beneficial anxiolytic effect.
Approximately 50% of patients with insomnia continue to have insomnia 3 years after initial
diagnosis, and many patients require months to years of treatment. Nonbenzodiazepines for primary
insomnia were found to have continued efficacy and to be well tolerated with no evidence of abuse
or withdrawal symptoms on discontinuation of use after 12 months.23,24 Ramelteon was also found to
be efficacious with no significant issues of abuse or tolerance in a 24-week open-label study.25 The
literature for longer use of hypnotics is scarce.
Anxiety disorders are frequently comorbid with alcohol or substance use disorders.4,26 Consider
ramelteon or low-dose sinequan to avoid potential issues of abuse and addiction.
Nonbenzodiazepines are preferred over benzodiazepines; there is evidence that the former have
decreased potential for abuse and a better adverse-effect profile.
In some patients with insomnia, benzodiazepines are clearly necessary. The other hypnotics may not
be as effective for some patients, and the anxiolytic properties of benzodiazepines may be helpful.
When hypnotics are used (particularly, benzodiazepines and nonbenzodiazepines), their use should
be reassessed—every 3 to 4 weeks.3,12 Many patients with insomnia do not experience sleep
disturbances nightly. Therefore, the use of hypnotics on an as-needed basis or a few times a week
helps cut down on the amount and exposure to medication.27
Trazodone and mirtazapine are also widely used for insomnia, as are atypical antipsychotics and
herbal preparations. Unfortunately, these agents have not been rigorously studied for insomnia and
thus their effectiveness and safety remain unclear.3
Nonpharmacological interventions
CBT-I is an important, widely accepted, multimodal treatment for insomnia and the best-studied of
the nonpharmacological approaches for this disorder. It is a manualized treatment that focuses on
various components of CBT (ie, cognitive restructuring and the use of psychological interventions,
such as the practice of good sleep hygiene, stimulus control, sleep restriction, and relaxation
therapy). These methods address negative and distorted cognitions and behaviors that initiate and
perpetuate insomnia.9,28 Treatment duration is relatively short. It is administered for 5 hours divided
over 4 to 6 weeks and can subsequently be used as a maintenance treatment in monthly sessions.
There are approximately 12 well-designed CBT-I trials that have clearly demonstrated that it is a
highly effective intervention for insomnia for 1 year or longer.29,30
Studies that compared CBT-I with pharmacotherapy found equivalent efficacy.31 This has led the NIH
Consensus and State of the Science Statement to conclude that CBT-I is “as effective as prescription
medications are for short-term treatment of chronic insomnia. Moreover, there are indications that
the beneficial effects of CBT, in contrast to those produced by medications, may last well beyond the
termination of active treatment.”3 In contrast to hypnotics, learned CBT-I skills may persist even
when active treatment ends.9 Furthermore, some patients may prefer CBT-I over hypnotic drugs
because of their possible adverse effects or because of concerns about drug interactions or taking a
drug during pregnancy.9
In general, CBT-I is underutilized—only about 1% of patients with chronic insomnia receive this
therapy.32 To increase the availability of CBT, it can be administered via self-help strategies (eg,
educational books and materials) and in group formats. In addition, the use of the Internet to provide
CBT has been shown to be effective. Nonetheless, patients frequently prefer face-to-face contact.33
Besides CBT-I, a number of other nonpharmacological therapies, such as bright light, physical
exercise, acupuncture, tai chi, and yoga, have been used to treat insomnia. Unfortunately, the
results have been inconsistent.32,34
Combination therapy
Is a combination of pharmacotherapy and nonpharmacotherapy more effective than either alone in
the treatment of anxiety disorders with insomnia? Combination therapy has not been addressed in
studies of this particular patient population. Furthermore, the question has been minimally
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addressed even in the treatment of insomnia per se. Study findings suggest only modest differences
in outcomes with a combination of therapies. Similar results were seen in a study that compared CBT
with CBT plus zolpidem. The 6-week acute study demonstrated a 60% response rate and a 40%
remission rate; the group with the combination treatment did have a significant increase in sleep
time of 15 minutes, but the researchers question the clinical significance of this isolated finding.29
Summary
Anxiety disorders with comorbid insomnia are highly prevalent with potential negative
consequences. Therefore, assess for insomnia with self-rating scales and careful clinical interviews.
When appropriate, refer patients for polysomnography.
Insomnia should be treated aggressively with pharmacotherapy, nonpharmacotherapy (particularly
CBT-I), or a combination. Some of the hypnotic treatments actually appear to facilitate successful
therapy for the anxiety disorder.
Benzodiazepines and nonbenzodiazepines have a number of adverse effects and can lead to abuse
and dependence. Patients with an anxiety disorder may be particularly vulnerable, especially those
with a history of alcohol and drug abuse. Treatment with benzodiazepine and nonbenzodiazepine
hypnotics needs to be reassessed monthly. Alternatively, ramelteon, low-dose sinequan, and CBT-I
should be considered because they have minimal adverse effects and no risk of abuse.
Successful treatment of insomnia is an important goal in patients with anxiety disorders. Both
pharmacological and nonpharmacological interventions have response rates of approximately 60%.
References:
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