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Sleep disturbances: a common and challenging symptom of post-traumatic stress disorder.

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EP continues its exploration of the effects of combat on servicemembers who have returned home and are attempting to cope with traumatic experiences while reintegrating into the daily life of family, community, and work. This series focuses on traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and related health issues. This month's article explores the effect of sleep disturbances and PTSD and some treatments being used to address these issues.

Sleep disturbances are a major sympton of post-traumatic stress disorder (PTSD). In the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision), the official diagnostic manual of the American Psychiatric Association (APA) in the diagnosis of PTSD, the presence of nightmares (recurrent distressing dreams of an event) is part of the DSM's Criterion B (reexperiencing of the traumatic event) and difficulty falling or staying asleep are part of Criterion D (increased arousal)--i.e., sleep disturbances comprise two of the five criteria required for the diagnosis of PTSD.

One or both of these features is experienced in up to 90 percent of patients with PTSD. These symptoms are considered particularly distressing by patients and have a highly negative impact on their quality of life (QOL). Additionally, there is evidence that impaired sleep contributes to physical and mental disorders associated with PTSD and is a contributor to the development and/or is a perpetuator of PTSD itself.

Sleep disturbances also play a role in substance abuse--especially alcohol abuse--as people attempt to self-medicate to avoid the distress associated with disturbed sleep and/or nightmares. Patients also respond to disturbances such as nightmares by engaging in behaviors in which they avoid sleep, resulting in insomnia. These sleep difficulties have a major adverse impact on patients with PTSD. The effective treatment of sleep disturbances is associated with beneficial consequences that go beyond improved sleep and decreased nightmares.

Seeking Effective Treatments

A variety of treatments have been tried, and some have shown greater results than others.

Unfortunately, sleep disturbances frequently do not respond to selective serotonin reuptake inhibitors (SSRIs), the major treatment for PTSD. Indeed, SSRIs may, at least initially, make insomnia more severe. The new generation of "atypical antipsychotics" (e.g.: quetiapine, olanzapine, and risperidone) may be helpful but are associated with side effects that include sedation and weight gain. Recently, however, new treatments have been developed that are more effective for sleep disturbances. These new treatments have been developed, in part, because of increased understanding of the pathophysiology (the accompanying functional changes) of PTSD.

Understanding Sleep

Sleep is divided into a variety of stages. The major division is that between rapid eye movement (REM) sleep and non-REM sleep. Most, but not all, dreams occur during REM. Additionally, during REM, the body is essentially paralyzed. The paralysis is useful in that it prevents people from acting out their dreams. The brain waves in REM are very rapid and desynchronized. NonREM sleep is divided into three stages. Here, we look first at the third stage. It is the deepest sleep and is known as slow-wave sleep (SWS), because the brain waves recorded during this type of sleep by electroencephalogram (EEG) are slow. They are also synchronized. It is thought that slow-wave sleep is the major restorative sleep. The amount of this sleep will determine whether you feel you have obtained a good night's rest when you awake in the morning. Stage 1 and 2 sleep is intermediate between REM and slow-wave sleep with respect to rate and degree of synchronization. While the majority of dreaming occurs during REM, it also occurs during other stages, particularly if the sleep is light and the sleeper can be easily awakened.

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Understanding PTSD and Sleep

It is thought that PTSD is associated with a failure to process and neutralize frightening memories. This failure allows frightening memories to push in during waking and sleeping hours. Because processing normally occurs during sleep, particularly REM sleep, and nightmares disrupt sleep, a vicious cycle begins, in which the processing of frightening memories is compromised. This has led to the use of a variety of psychotherapies to enhance processing and neutralization of frightening memories to decrease their ability to disturb sleep and to enhance sleep-mediated processing of disturbing thoughts. Alternatively, there are medications that decrease disturbing dreams. The effect of medications on processing frightening memories is unclear, but the two approaches may be complementary since medications may be helpful in breaking the vicious circle noted above.

All Systems Not Go: Some of the Difficulties

Stress in general, and PTSD, in particular, is thought to be associated with activation of the noradrenergic system (NAS). The noradrenergic system consists of the neurotransmitter norepinephrine and its receptors, which are found in the central nervous system and throughout the body--on nerves, blood vessels, and organs, including the heart. There are many types of noradrenergic receptors, alpha (alpha1 and alpha 2) and beta. The noradrenergic system is thought to play a role in the transition from acute stress disorders to chronic stress disorders and to be central to the symptoms in established cases of PTSD. Alpha receptors are believed to have the predominant role in these symptoms, including sleep disruption and intrusions of unwanted and frightening thoughts while patients are awake or asleep. The understanding of the role that the noradrenergic system plays has led to the use of medications that block the noradrenergic system as a way of treating sleep disorders and nightmares.

Evidence for the role that the noradrenergic system plays includes the following: Many of the areas of the brain thought to be associated with PTSD symptoms are heavily stimulated by noradrenergic (NA) neurons and express a high density of noradrenergic receptors. They are very responsive to activation of the system. Furthermore, concentrations of noradrenergic neurons in the cerebrospinal fluid (CSF) are highly correlated with the severity of symptoms of PTSD, and excretion by noradrenergic neurons of Norepinephrine and its metabolites are increased in the urine of patients with PTSD.

Laboratory studies show that increased noradrenergic activity has a variety of bad effects on a person's REM sleep. These include the diminishing of REM-associated paralysis, leading to increased movements during REM, which may lead to waking up. In addition, shifts from REM to other stages are increased. Thus, noradrenergic system activation is associated with REM fragmentation (waking up throughout the night, reducing the total amount of time spent in the deeper levels of sleep). Poor-quality REM sleep, in addition to leading to awakenings, also prevents a person from processing stressful memories. This leads to waking up more often and decreased processing. In addition, NA stimulation is associated with the lightening of types of sleep other than REM and increased levels of corticotrophin releasing factor (CRF). Corticotrophin releasing factor is a hormone produced by the hypothalamus that leads to anxiety, including an increase in a person's primitive internal alarm system. Furthermore, it leads to release of Norepinephrine by noradrenergic neurons, which in turn leads to further release of corticotrophin releasing factor, again, increasing a person's anxiety level.

The Role of Medications

All this suggests that medications that interfere with the noradrenergic system might be useful in PTSD. Clonidine is one such medication. It is an activator (agonist) of the type 2 alpha receptor, a receptor that decreases noradrenergic neuron release of Norepinephrine. Thus, clonidine causes the noradrenergic system to regulate down. Its major use in medicine is to treat hypertension--hence, hypotension is one of its side effects. Its peak effect occurs one to three hours after it is taken by mouth, and a usual dosage is .2 to .4 mg. Aside from hypotension, bad side effects are dry mouth, drowsiness, and constipation. The beneficial effects may wear off in time, requiring an increase in the dosage. There have been a number of reports of its successful use for those with PTSD, particularly in children.

Recently, most studies of medications to regulate the noradrenergic system have focused on prazosin, which blocks the alpha1 receptor. It is used for hypertension and urinary difficulties that are secondary to a non-life threatening enlargement of the prostate. Multiple studies of this medication have shown its use for the treatment of PTSD, particularly for the treatment of nightmares and sleep disturbances. Interestingly enough, it specifically decreases the abnormal nightmares that occur with PTSD. Normal nightmares and normal dreams have been reported to increase after its administration, as stress-related nightmares decrease. In addition, using it has led to a decrease in difficulties falling asleep and staying asleep. A decrease in PTSD symptoms other than those associated with sleep and decreased ratings of depression have also been reported. One study reported that prazosin was associated with increased total sleep as well as more REM sleep (consistent with return of normal dreaming) as well as an increase in the number of eye movements during a period of REM sleep and less time between falling asleep and the first period of REM sleep. Patients who had failed to respond to other treatments (e.g., SSRIs tricyclic antidepressants (TCAs)) have responded to this drug, which may indicate the superiority of prazosin to these other treatments. On the other hand, since in many trials patients continued on previous medications, these results may indicate prazosin's use as an additional medication to SSRIs, tricyclic antidepressants, and others.

While many of the trials have been open trials, a number of them have been placebo-controlled and crossover, providing compelling evidence for the effectiveness of prazosin. While protocols using up to 20 mg have been described, most studies have shown good results with 2 to 6 mg. Higher doses are divided, but doses of 2 to 6 mg are given at bedtime. A test dose of one mg is given, with the dosage increased every 3-7 days as needed until effective or until side effects decrease. While some patients experienced a drop in blood pressure when standing, many of these were also on anti-hypertensives or other cardiac medications. Prazosin's peak effect occurs 1 to 3 hours after being taken by mouth, its half-life is 2 to 3 hours, and its effect lasts 4 to 6 hours. The most common side effect is nasal congestion, with hypotension and sedation being rare. Dosage increases may occasionally be required. A return of sleep problems occurs when a person stops using prazosin, consistent with prazosin suppressing nightmares rather than helping in the processing of the underlying traumatic memories.

Thus, prazosin has demonstrated effectiveness in treating sleep disturbances and nightmares and has had a favorable effect on other symptoms of PTSD. Whether or not the decrease in symptoms, other than sleep symptoms, is secondary to improved sleep or primary, prazosin should be considered a first-line medication for sleep disturbance. It avoids the potential disadvantages of other agents such as tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and benzodiazepines (used especially as tranquilizers), which include suicide risk, medical adverse effects, and in the case of benzodiazepines, substance abuse, and only has variable effectiveness.

Thoughts in the Field

Despite the attention paid to sleep disturbances as symptoms that occur with PTSD, certain investigators think the importance of sleep disturbances may have been downplayed and that certain types have been neglected. They contend that insomnia and nightmares should be considered core symptoms of PTSD, which may actually cause and perpetuate the disorder. Furthermore, they suggest that sleep-disordered breathing (SDB) (abnormal breathing patterns that interfere with sleep) and periodic arm and leg movements in sleep (PLMS) are important contributors to PTSD sleep disturbances and have been largely ignored.

In support of the idea that sleep disturbances may cause PTSD, they cite studies reporting that sleep disturbances occurring during the period of the stress reaction right after the stressful event are strong predictors of the development of PTSD. There is even a report that sleep disturbances occurring before the stressor may predict the later occurrence of PTSD. The plausibility of these reports is supported by observations that sleep deprivation is well known to interfere with a person's ability to cope in general and to impair mood. Furthermore, as discussed, normal sleep, including REM, is thought to play a role in processing memories of trauma, which are central to PTSD. All of these may increase a person's vulnerability to PTSD. Consistent with this possibility, there are reports that early treatment of sleep disturbances during periods of acute stress may prevent the development of PTSD, and a number of studies have shown that treatments directed at sleep disturbances and nightmares may decrease other symptoms of PTSD. While treatments that focus on traumatic memories may decrease symptoms of PTSD, unless attention is paid to sleep disturbances, patients often continue to suffer from insomnia and nightmares, which, according to these models, may perpetuate PTSD.

The possible interactions of sleep disturbances and PTSD are compatible with several models of the relation of stress, sleep, and PTSD, each of which may hold for different patients: 1) Sleep abnormalities, regardless of cause, predispose one to the development of PTSD after an acute stressor; 2) Sleep abnormalities resulting from acute stressors may cause PTSD--i.e., sleep disturbances mediate the relationship between acute stress and PTSD; and 3) Sleep disturbances and other PTSD symptoms develop in response to the acute stressor, and sleep disturbances may be resistant to standard PTSD therapies that do not explicitly deal with them. If any of these three relationships hold, it is clear that treatments must explicitly focus on sleep disturbances to obtain optimal results with PTSD.

Fine-Tuning Understanding

Recent studies have indicated that PTSD is often associated with sleep-disordered breathing. Two explanations for this association have been advanced, both of which are plausible and may cooccur. As has been described, sleep, including REM sleep, is broken up in patients with PTSD. It has been shown in experimental settings that such sleep fragmentation is associated with an increased tendency for airway collapse. While such airway collapses may not be of magnitude to cause sleep apnea (a temporary suspension of breathing occurring repeatedly during sleep), with its easily observable arousals, gasping for breath, snoring, etc., they can cause hypopneas (abnormally slow, shallow breathing), which trigger microarousals that serve to restore sufficient airflow--i.e., hypopneas lead to further sleep fragmentation. This is known as upper airway resistance syndrome (UARS). These apneas or hypopneas have been shown to lead to nightmares or at least to impart negative emotional tones to the dreams associated with them. Thus, it is clear how a vicious cycle could result, leading to both nightmares and fragmented sleep.

Disruptions of other phases of sleep lead to lack of restorative sleep (sleep that leaves a person feeling that he or she has had a good night's rest). This decrease is often associated with daytime sleepiness and/or a lack of energy. Other signs of sleep-disordered breathing include: morning headaches, dry mouth, nocturia (waking up to urinate), and cognitive-affective disturbances, which include depression, anxiety, attentional problems, and memory disturbances, among others. Since upper airway resistance syndrome may require state-of-the-art technology for its detection, sleep-disordered breathing often remains undetected and hence ignored. Aside from the technical difficulties associated with the detection of subtle forms of sleep-disordered breathing, their neglect in part results from the tendency of both doctors and patients to focus most on the psychological aspects of PTSD as the explanation of symptoms, including sleep disturbances.

It has been proposed that in at least some cases, sleep problems that persist after psychological and/or pharmacological treatments result from sleep-disordered breathing continuing. Indeed, it has been shown that in some cases, treating PTSD by continuous positive airway pressure (CPAP) alone, which is the gold-standard treatment for sleep-disordered breathing, and without any psychological intervention, not only alleviates sleep problems but can also cause a dramatic relief from other PTSD symptoms, underscoring the potential causal or mediating role of sleep problems, including sleep-disordered breathing in the genesis of PTSD. Since many patients with PTSD find that continuous positive airway pressure may produce claustrophobia and anxiety, conservative approaches such as instruction to sleep on the side instead of the back, attention to nasal hygiene, or the use of nasal dilator strips may be used first. The latter techniques clear the nasal passages, thus decreasing airway resistance and, hence, mini-collapses. Periodic limb movements in sleep, which disrupt and fragment sleep are also increased in patients with PTSD, probably due to increased noradrenergic tone.

Psychological Treatments

In addition to medication and treatments for underlying sleep-disordered breathing, there are a variety of psychological approaches to the treatment of sleep disturbances. One of these, imagery rehearsal therapy (IRT), focuses on the symptom of disturbing nightmares. In this treatment, patients are taught techniques of imagery and how to apply these to their nightmares. Two types of instructions have been employed that are equally effective.

In one of these, patients are asked to remember a nightmare, write it down, and then change the ending in any way they deem helpful and rehearse the new "dream." This is often done in group sessions. This technique has been shown to have ongoing positive effects on the number of nightmares per week and the number of nights without nightmares. Furthermore, insomnia is often improved because of the decrease in sleep disturbances resulting from nightmares and a decrease in protective behaviors adopted in attempts to ward off nightmares. (These protective behaviors include: delaying bed time, getting out of bed when waking rather than trying to get back to sleep, sleeping with lights on, substance abuse, and others). PTSD symptoms often decrease as sleep improves. Some patients find that imagery rehearsal is stressful and may increase fears. These negative effects may be decreased by first teaching patients how to employ pleasant imagery and having them start with less fear-inducing dreams (e.g., those not dealing explicitly with the traumatic events and limiting imagery rehearsal therapy to one dream per week).

A second form of psychotherapy dealing with sleep issues is Sleep Dynamic Therapy[R] (SDT), which includes a multitherapeutic focus on sleep issues in addition to imagery rehearsal therapy for nightmares. Sleep Dynamic Therapy consists of six two-hour sessions given weekly in a group format with an emphasis on psychoeducation and sleep-directed cognitive behavioral therapy (CBT). Sleep-directed cognitive behavioral therapy involves identifying stimuli that either interfere with or help with sleep, together with identification and abandonment of maladaptive habits that interfere with sleep. The psychoeducation includes identification of symptoms of sleep problems, including lack of restorative sleep, daytime sleepiness, and frequent awakenings, etc., which are often ignored because of the other obvious symptoms of PTSD. In addition, proper bedtime habits (good sleep hygiene) are taught.

Increasing Understanding

While the importance of nightmares and insomnia as symptoms of PTSD has long been appreciated, it is increasingly becoming apparent that this may be only the tip of the iceberg. Other types of sleep abnormalities such as sleep-disordered breathing and periodic limb movements in sleep are apparently common and may play a role in insomnia or nightmares. Importantly, not only are sleep disturbances major sources of distress for patients with PTSD, but they may play key roles in causing or perpetuating the disorder. They may also contribute to substance abuse, particularly of alcohol. While alcohol may help patients fall sleep, there is a rebound awakening. Furthermore, sleep worsens during withdrawal. These factors lead to increasing amounts of alcohol consumption. Fortunately, there are an increasing number of treatments available for sleep disturbances (e.g., imagery rehearsal therapy, Sleep Dynamic Therapy, pharmacotherapy, and, in some cases, continuous positive airway pressure). Yet in order for these treatments to be effective, the sleep problems must be noted. While it is hoped that clinicians are becoming more aware of the prevalence and importance of sleep disturbances, it behooves the patient to bring them forward if the clinician does not focus on the issue.

Patients' descriptions of sleep disturbances are the gold standard for their identification. While polysomnograpy (EEG, eye movement, and muscle activity measurements obtained during sleep) may be helpful in identifying and/or confirming some cases of sleep disturbances, there are many false negatives. This is because sleep laboratories, and even home monitoring, induce feelings of safety in many patients with PTSD. The partner may supply invaluable information regarding sleep-disturbance symptoms.

Determining a Person's Options

Further studies are required to determine how to optimally use the great variety of treatments now available for sleep disturbances, including nightmares, associated with PTSD. Among the questions requiring answers is this one: Is there one "best" treatment or, as is more likely, are different clinical patterns associated with different responses to a given treatment? Medications may improve sleep and decrease nightmares while psychotherapy may help with the reprocessing of traumatic thoughts. Since at least some good-quality sleep is required for optimal reprocessing, the two techniques are likely complementary. In view of this, should medications and psychological therapies then be used at the same time or in sequence? These and many other questions need to be answered.

Since it is likely that different treatments and/or their combinations may be required for a given patient, patience and persistence will be required while sequential trials are performed. But it is fair to say that this should be done with a spirit of optimism and conviction that an effective treatment regimen will be found. Not only may such treatments alleviate a decreased quality of life for individuals due to sleep disturbances, but they may also improve other PTSD symptoms.

By James Halper, MD

James Halper, MD, is Clinical Associate Professor of Psychiatry at New York University School of Medicine, working with the Brain Research Laboratories of NYU's Langone Medical Center, and Attending Psychiatrist at Lenox Hill Hospital. He has a private practice in New York City. He is board-certified in psychiatry and medicine.
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Title Annotation:TRAUMATIC BRAIN INJURY/POST-TRAUMATIC STRESS DISORDER SERIES: PART FOUR
Author:Halper, James
Publication:The Exceptional Parent
Geographic Code:1USA
Date:Nov 1, 2008
Words:3611
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