Thomas C. Neylan, MD

The National Comorbidity Survey estimates that approximately 50% of the population in the United States is exposed to traumatic events and that the lifetime prevalence of posttraumatic stress disorder (PTSD) is approximately 7.8%.

 Multiple studies have demonstrated that patients with PTSD complain of recurrent nightmares and sleep continuity disturbances, which are listed separately in the re-experiencing and hyperarousal clusters in 

Sleep disturbances have been described in female rape victims as well as in a heterogeneous sample of women with PTSD.

 A study of 116 Vietnam veterans receiving treatment in a PTSD specialty clinic found that disturbed sleep (separate from nightmares) was the most frequently reported symptom (in 90% of participants).

 Recent data from soldiers returning from service in Iraq have shown that sleep disturbances and associated daytime fatigue were the most frequently reported symptoms in those with PTSD.

 Overall, there are ample data that sleep disturbances are a potent source of distress in patients with PTSD.

Insomnia and other sleep disturbances occur frequently in patients with PTSD and they can be severe. Consequently, more than half of affected patients are treated with sedating antidepressants or sedative hypnotics.

Recurrent nightmares are a signature feature of PTSD.

 Patients often report sleep phobia, in part because they dread the nightmares and the associated feeling of helplessness.

 Recurrent nightmares, sleep phobia, and chronic insomnia provide a strong conditioning context for associating the bedroom with anxious arousal. This becomes even stronger for sexual assault victims who may have experienced the traumatic event in the bedroom. Thus, patients with PTSD have difficulty in relinquishing a defensive posture that is critical for inducing normal healthy sleep.

Findings from objective studies using polysomnography show increased sleep continuity disturbances in patients with PTSD compared with controls. This was evidenced by decreased total sleep time, frequent arousals, particularly in rapid eye movement (REM) sleep, and increased motor activity during sleep. However, a few studies did not find differences in objective sleep measures among patients with PTSD and controls.

 The emerging evidence suggests that subjective complaints of sleep duration and sleep fragmentation are more prevalent and severe than the objective measures. This has raised the question of whether patients with PTSD have intact hypervigilance during light stages of sleep. This fits clinically with the frequent report from patients that they “sleep with one eye open.”

Disturbed sleep is associated with a wide range of adverse conditions. Subjectively, these include fatigue, cognitive impairment, mood disturbance, and reduced quality of life.

 Objectively, disturbed sleep has been associated with poorer job performance and increased frequency of accidents, aggression, and use of alcohol.

 Furthermore, there is a large body of evidence that demonstrates that chronic sleep loss is associated with poor psychomotor performance, especially when tasks require sustained vigilance.

 Compounding such effects is the inability of many sleep-deprived persons to self-monitor their sleepiness or performance deficits.

Multiple prospective studies have found that disturbed sleep predicts future mood and anxiety disorders. Data from the NIMH Epidemiologic Catchment Area study show that insomnia predicts new-onset depression and anxiety disorder.

 Disturbed sleep is associated with increased substance use and abuse and major depressive disorder.

 Also, disturbed sleep and nightmares are associated with increased risk for suicide.

In addition, disturbed sleep increases the risk of obesity, diabetes, impaired immunocompetence, hypertension, and cardiovascular disease. In a large survey of police officers, PTSD symptoms were significantly related to both somatic symptoms and health functioning. The relationship between somatic symptoms and traumatic stress symptoms was strongly affected by sleep, and the relationship between health functioning and traumatic stress symptoms was fully affected by sleep.

The first step in helping patients with PTSD-related sleep disturbances is to conduct a thorough medical and psychiatric history with a particular focus on sleep-wake function. The entire 24-hour period should be explored with respect to sleep-wake habits. Patients should be questioned about their views on what constitutes healthy sleep. A practical criterion for evaluating the severity of insomnia, for example, is to put greater weight on reports of daytime impairment as opposed to reports on the length of sleep duration.

Patients with PTSD may not accurately estimate their sleep times, so it is useful to focus on whether they feel restored during the day. Self-rating instruments such as the Insomnia Severity Index and the Pittsburgh Sleep Quality Index Addendum for PTSD are useful for measuring subjective sleep quality.

 A 2-week sleep-wake log is invaluable for obtaining a history of irregular sleep-wake patterns; napping; use of stimulants, hypnotics, or alcohol; diet; activity during the day; number of arousals; and perceived length of sleep time and its relationship to daytime mood and alertness. Patients should be asked about symptoms of morning headaches, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis.

In addition, they should be questioned carefully about falling asleep while driving or while performing any other potentially dangerous activity. Additional history should be obtained from bed partners for events usually not perceived by the patients, such as snoring, respiratory pauses longer than 10 seconds, unusual body movements, or violent motor behavior. Concerns about sleep apnea, narcolepsy, or excessive sleep-related motor behavior should prompt a referral to a sleep laboratory for di-agnostic polysomnography. Sleep apnea, when present, should be aggressively treated given its potential for aggravating PTSD-related nightmares and insomnia.

There are a small number of published trials of psychological treatment for both nightmares and insomnia in patients with PTSD. Most focus on sleep hygiene and core elements of cognitive-behavioral therapy for insomnia (CBT-I). Sleep hygiene focuses on stabilizing the time of sleep-wake activity; sleeping in a comfortable, quiet, and cool setting; avoiding stimulants and alcohol; and getting regular exercise. Sleep hygiene is undoubtedly good advice but may be difficult to implement in some patients. PTSD is associated with a sense of foreshortened future, and some patients do not always adhere easily to preventive health practices.

One element of CBT-I, stimulus control behavior modification, focuses on eliminating the conditioned linkage of the bedroom with arousal.

 Patients are instructed to use their bed only for sleep and intimacy, to go to bed only when sleepy, to get out of bed and leave the bedroom when unable to sleep, and to return to bed only when ready to fall asleep. The overall goal is to extinguish the conditioned arousal associated with being in bed, simply by drastically limiting the amount of time lying in bed awake. Patients who awaken during the night are instructed to leave the bedroom. With practice, patients sleep more continuously and efficiently and no longer mount a conditioned arousal response when they get into bed.

A complementary technique used in CBT-I is called sleep restriction therapy.

 Patients monitor the time they spend in bed with a sleep diary and estimate the amount of time awake or asleep each night. They are then instructed to adjust their time in bed with the goal of reaching a sleep efficiency of around 90%. Because patients with insomnia often compensate by extending time in bed to increase sleep opportunity, they develop a pattern of sleeping with low efficiency. Sleep restriction reduces time in bed, and initially results in some sleep loss. Over time, patients sleep more efficiently, and time in bed can be gradually liberalized. There is one pilot study of CBT-I that was given to 5 PTSD patients with residual insomnia after completing exposure therapy for PTSD. CBT-I was found to be effective in this small sample.

 have reported on the effects of imagery rehearsal therapy in several studies in PTSD patient with repetitive stereotypic nightmares. The results have been promising, but the treatment is not always well tolerated.

 Imagery rehearsal therapy by necessity requires an exploration of dream narrative and hence involves some elements of trauma exposure therapy. Germain and colleagues

 found that a single session employing aspects of imagery rehearsal therapy with CBT-I was effective in a pilot sample of PTSD patients.

Overall, there is promising data that psychological treatments for PTSD-related sleep disturbances can be effective. The main limitation is that these techniques have not been widely disseminated and involve interventions that require some specialized training. Fortunately, training programs for CBT-I are becoming more available and there are a growing number of Web-based resources for patients such as the National Center on Sleep Disorders Research (

http://www.nhlbi.nih.gov/about/ncsdr/patpub/patpub-a.htm

At present, there are only 2 medications approved by the FDA for the treatment of PTSD. Both of these are SSRI antidepressants, which are associated with frequent complaints of sedation and insomnia. Although SSRIs are effective in civilian patients with PTSD, the results of a multicenter sertraline PTSD trial and 2 placebo-controlled fluoxetine trials in US military veterans were negative.

 In patients who have a significant treatment response to SSRIs, there generally is a reduction in nightmares and improvement in insomnia.

-adrenergic antagonist, has been found to have positive benefits for nightmares and insomnia in 2 placebo-controlled trials that enrolled veterans who had chronic PTSD.

 Findings from these trials suggest titrating prazosin from an initial dose of 1 mg up to 15 mg at bedtime. Clinicians and patients should be aware of a significant hypotensive response to the first dose. Significant hypotension is generally not seen after repeated dosing, even with upward titration. Patients should be warned of possible hypotensive responses to coadministration of prazosin with phosphodiesterase-5 inhibitors used for treatment of erectile dysfunction. Recently, the Department of Veterans Affairs initiated a large-scale, multicenter, placebo-controlled study of prazosin that focuses on trauma nightmares, sleep disturbance, and global clinical status. The results of this trial will definitively address whether prazosin should be considered as a first-line treatment for PTSD-related sleep disturbances.

The success of prazosin is support for the hypothesis that PTSD is associated with increased CNS adrenergic activity.

 However, 2 controlled trials with guanfacine, an alpha

-presynpatic agonist, have been negative.

 A large propranolol PTSD prevention trial in recently traumatized civilians was also clearly negative; it failed to confirm findings from 2 smaller studies that indicated a trend level effect of propranolol for PTSD prophylaxis.

 Compounding these failures is the recognized tendency of beta-adrenergic blockade to intensify dreams, an effect that may have amplified trauma-related nightmares in several combat veterans treated with propranolol.

 Hence, the role of antiadrenergic pharmacotherapy appears to be limited at present to postsynaptic alpha

-blockers. Prazosin is currently the only alpha

-blocker that has any significant effects in the brain.

Sleep disturbances are associated with an increased risk for physical health complaints, diminished ability to cope with stress, and a reduced capacity to carry out daily activities. CBT for insomnia has shown some promise for addressing insomnia complaints. It remains to be seen whether CBT-I without a focus on trauma experiences can reduce nightmares. Sedative-hypnotic drugs are virtually untested for PTSD despite the prominence of sleep complaints. More randomized controlled trials are needed to produce the evidence that will guide rational treatment.



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Thomas C. Neylan, MD

Articles

Sleep Disturbances Associated With Posttraumatic Stress Disorder