Insomnia and Anxiety (Series in Anxiety and Related Disorders) (18 page)

enter treatment medication free. It also seems useful to question if there is an opti-

mal treatment protocol for people who wish to combine CBT with pharmacother-

apy for insomnia. Finally, it seems useful to ascertain if CBT and other psychological

techniques are useful to those who exhibit hypnotic-dependence who ultimately

wish to discontinue their sleep medication use.

These questions are of critical importance to the CBT therapist, and for this

reason, a substantial proportion of this chapter is devoted to thoroughly

addressing them. However, before embarking on this discussion, it seems nec-

essary to provide some background information about prescription hypnotic

(sleep) medications as well as about the nonprescription products that are com-

monly used as sleep aids. Given the focus of this text, it also seems important

to consider how various agents commonly prescribed for anxiety disorders

might affect the sleep of patients who suffer from insomnia and such comorbid

conditions. Hence, the ensuing three sections provide discussions of these

topics. This information should lead to a better understanding of CBT imple-

mentation with medicated patients.

Prescription Hypnotics: Advantages and Disadvantages

65

Prescription Hypnotics: Advantages and Disadvantages

It is estimated that insomnia sufferers spend well over $285 million per year on

medications prescribed to aid their sleep (Walsh & Engelhardt, 1999). The most

frequently prescribed hypnotic medications are benzodiazepine receptor agonists

(BzRAs) (Wagner, Wagner, & Hening, 1998; Walsh & Engelhardt, 1999). These

include several benzodiazepines (e.g., temazepam, triazolam, estazolam, quaze-

pam, flurazepam) and newer nonbenzodiazepine agents (e.g., zolpidem, eszopi-

clone, zaleplon) that act at the same binding site on the GABA-A receptor complex.

In addition to these medications, sedating antidepressant drugs such as trazodone

(TRZ) and several sedating tricyclic antidepressants (e.g., amitriptyline, doxepin)

as well as newer generation antipsychotics (e.g., olanzapine, quetiapine) have been

used widely for insomnia treatment (Walsh & Engelhardt, 1999) despite varying

evidence for efficacy. Finally, the melatonin agonist ramelteon recently has been

approved for insomnia management.

Of the various prescription medications used for insomnia treatment, BzRAs

have the greatest amount of efficacy and safety data. Both traditional and newer

BzRAs have undergone rigorous premarket safety/efficacy trials and are FDA

approved for insomnia management. A meta-analysis (Nowell et al., 1997) of 22

placebo-controlled trials involving traditional BzRAs and zolpidem in patients with

primary insomnia showed that these agents produce reliable short-term (median

treatment duration = 7 days; range = 4–35 days) improvements of sleep-onset

latency, number of awakenings, total sleep time, and sleep quality. Furthermore, the

newer BzRAs such as eszopiclone may have continued efficacy and safety for peri-

ods of 3–12 months of nightly use (Krystal et al., 2003; Roth, Stubbs, & Walsh,

2005). Like the BzRAs, ramelteon is FDA-approved for treatment of insomnia, but

published efficacy and safety data for this medication are currently more limited.

Trazodone and most sedating tricyclic antidepressants have very limited empirical

support for insomnia management, and they lack FDA approval for such use.

Curiously, these agents remain relatively popular and are used widely “off-label”

for insomnia treatment (Walsh & Engelhardt, 1999).

Prescription hypnotics and particularly the BzRAs have a number of advantages

that support their continued use in primary care and other medical settings. BzRAs

are widely available, easy to administer, and they are generally well tolerated by

patients. Furthermore, they typically produce rapid sleep improvements usually on

the first night they are taken. Given this latter feature, such prescription hypnotics

would seem to be the treatments of choice for treating cases of transient or short-

term sleep problems. For example, they seem ideal for helping a person sleep in

response to stressful life circumstances (death of a loved one), or following an

abrupt change in one’s sleep–wake schedule as occurs in jet lag. Likewise, they are

useful for those who intermittently have difficulty sleeping due to episodic, albeit

recurrent, stressful circumstances, such as special assignments at work or before

giving a speech or presentation to the public. In fact, sleep medications may be

favored over a psychological/insomnia therapy for the management of these various

forms of transient insomnia.

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5 Medication Considerations

However, there are a number disadvantages incumbent in the range of sleep

medications that may make them less desirable for long-term insomnia manage-

ment. Long-acting BzRAs (e.g., flurazepam) may have “hang-over” effects, leading

to more motor and cognitive impairment, especially among older age groups

(Roehrs, Kribbs, Zorick, & Roth, 1986; Roth & Roehrs, 1991). Long-acting

BzRAs also have been blamed for an increased rate of motor vehicle accidents

(Hemmelgarn, Suissa, Huang, Boivin, & Pinard, 1997) and hip fractures (Ray,

1992) among older age groups. The shorter acting agents, with rapid onset and

offset of effects, are less prone to these sorts of problems, although residual day-

time effects may occur with these in some individuals, particularly the elderly,

when higher doses are prescribed. More common among the shorter acting agents

are such problems as anterograde amnesia (Jonas, Coleman, Sheridan, & Kalinske,

1992; Wysowski & Barash, 1991), which in some individuals may lead to episodes

of sleep-related cooking or driving a motor vehicle (US Food and Drug

Administration, 2007). Also common to the shorter acting agents are such prob-

lems as drug tolerance and the phenomenon of rebound insomnia (Greenblatt,

1992), a dramatic worsening of sleep occurring when the agent is abruptly discon-

tinued or withdrawn. And, as will be discussed in more detail later, all sleep aids

are associated with the risk of dependence, particularly psychological dependence

that results in persistent difficulty sleeping and increased sleep-related anxiety

upon their discontinuation.

Given the noted disadvantage of sleep medications, many healthcare providers

have traditionally had some reluctance to prescribe these agents on a long-term

basis for insomnia management. This reluctance has been attenuated somewhat by

recent studies (Krystal et al., 2003; Roth, Walsh, Krystal, Wessel, & Roehrs, 2005)

showing continued safety and efficacy of some of the newer generation hypnotics

over extended periods of continuous use. Nonetheless, it should be noted that there

are currently no data to demonstrate that people are able to maintain the sleep

improvements they obtained with any of the available prescription hypnotics after

such medications are discontinued. Moreover, at least one study (Morin, Gaulier,

Barry, & Kowatch, 1992) has shown that those with insomnia expect that psycho-

logical therapies will produce more positive results with fewer treatment-related

side effects than will pharmacotherapy for insomnia. Given these considerations,

CBT may be favored over the prescription sleep aids by many of those with chronic

sleep difficulties.

Over-the-Counter Medications, Herbal Remedies,

and Alternative Treatments

Many, if not most, of those who desire treatment for their insomnia will initiate treat-

ments on their own without seeking medical advice of consultation. Although various

self-help books (Edinger & Carney, 2008; Hauri, 1996; Jacobs, 1999; Morin &

Wooten, 1996) are available that describe psychological strategies for managing

Over-the-Counter Medications, Herbal Remedies, and Alternative Treatments

67

insomnia, most self-treating insomnia sufferers resort to some form of nonprescription

sleep aid. Included among these are over-the-counter compounds specifically

marketed as sleep aids, herbal and dietary supplements that are presumed to have

sleep benefits or sleep-inducing qualities, and alcoholic beverages. In general,

these compounds have, at best, limited data to support their effectiveness for

insomnia management and many may result in undesirable side effects or even

adverse reactions. Moreover, as is the case with the prescription sleep aids,

people may develop a psychological dependence on such agents with their continued

use. A detailed summary of the range of publicly available compounds used as

sleep aids is beyond the scope of this text. However, the following provides a

brief overview of the general categories of substances commonly used as self-

help sleep aids.

Antihistamine-Based Sleep Aids

A variety of over-the-counter agents are manufactured and FDA approved specifi-

cally as sleep aids. These agents are sold under numerous brand names but all such

products marketed specifically for treating insomnia contain diphenhydramine (i.e.,

benedryl) or doxylamine as their active, sedating compound. Some such products

contain one or the other of these compounds as the sole active ingredient whereas

some products combine one of these compounds with an analgesic (e.g., aspirin,

acetometaphan) and are targeted for patients who have insomnia in the context of

ongoing pain. Both diphenhydramine and doxylamine act on the H-1 hystamine

receptor and block the effects of histamine, an alerting neurotransmitter found in

the central nervous system. As such, ingestion of these compounds leads to subjec-

tive drowsiness and sleepiness, thus leading to their use as insomnia therapies.

Clinical studies in which doses of 12.5–50 mg of such compounds were used have

shown subjective improvements in various sleep measures (Buysse, Germain,

Moul, & Nofzinger, 2005; Morin, Beaulieu-Bonneau, LeBlanc, & Savard, 2005).

However, a recent study showed that objective sleep recordings failed to corrobo-

rate improvements noted on self-reported sleep measures (Morin et al., 2005).

Nonetheless, the subjective benefits of these compounds seem sufficient to lead to

their current widespread use by the general public.

Although these products are sold without a prescription, they are not without

notable side effects. Daytime sedation or “hangover” and impairments of psycho-

motor performance are commonly reported (Buysse et al., 2005; Meoli et al., 2005).

Other reported side effects include dizziness, nausea, depression, malaise, dry

mouth, weakness, headaches, tinnitus, gastrointestinal distress, impotence, and

voiding problems (Buysse et al., 2005; Meoli et al., 2005). In a minority of users,

paradoxical effects including restlessness, anxiety, and increased alertness seem to

occur. Impaired cognition is also noted in a large percentage of older hospitalized

adults who are given such compounds as sleep aids (Agostini, Leo-Summers, &

Inouye, 2001). In general, these compounds are contraindicated in those with

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5 Medication Considerations

narrow angle glaucoma. Serious, life-threatening side effects are extremely rare but

have been described in selected case reports (Buysse et al., 2005).

Herbal Compounds and Dietary Supplements

A variety of herbal compounds and dietary supplements are sold as sleep aids.

Included among these are valerian root, kava kava, hops, St. John’s Wort, lemon

balm, Jamaican dogwood, California poppy, passion flower, and lavender. With the

exception of valerian root, data are lacking concerning the safety and efficacy of

most of these compounds for insomnia treatment. In the case of valerian root, the

results concerning treatment efficacy have been mixed. A recent study showed

some subjective benefits of a valerian root/hops combination in the treatment of

primary insomnia. However, concurrent objective sleep recordings did not corrobo-

rate these subjective benefits. In other trials, valerian root has produced some sub-

jective and objective sleep benefits (Donath, Quispe, & Diefenbach, 2000; Schulz,

Stolz, & Müller, 1994). Thus, despite the mixed findings, it seems valerian prepara-

tions may produce sleep benefits for some users.

Currently, there are very limited safety data concerning this class of compounds.

Side effects associated with valerian generally have been mild and include morning

sleepiness, lightheadedness, weakness, and headache (Buysse et al., 2005). In rare

cases, hepatoxicity has been associated with the use of valerian and kava kava,

whereas there is one report of heart failure and delirium upon the abrupt withdrawal

of valerian (Meoli et al., 2005). Currently, data are lacking concerning the safety of