Savvy Psychopharmacology

PTSD nightmares: Prazosin and atypical antipsychotics

Current Psychiatry. 2012 June;11(6):59-67

References

1. Dohrenwend BP, Turner JB, Turse NA, et al. The psychological risks of Vietnam for U.S. veterans: a revisit with new data and methods. Science. 2006;313(5789):979-982.

2. Tanielian T, Jaycox L. eds. Invisible wounds of war: psychological and cognitive injuries, their consequences, and services to assist recovery. Santa Monica, CA: RAND Corporation; 2008.

3. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington DC: American Psychiatric Association; 2000.

4. Wittmann L, Schredl M, Kramer M. Dreaming in posttraumatic stress disorder: a critical review of phenomenology psychophysiology and treatment. Psychother Psychosom. 2007;76(1):25-39.

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16. Peskind ER, Bonner LT, Hoff DJ, et al. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder. J Geriatr Psychiatry Neurol. 2003;16(3):165-171.

17. Raskind MA, Dobie DJ, Kanter ED, et al. The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. J Clin Psychiatry. 2000;61(2):129-133.

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Practice Points

• Prazosin is recommended as a first-line therapy for nighttime PTSD symptoms, such as nightmares or sleep disturbances—especially among veterans—because of superior long-term effectiveness.

• Risk of metabolic syndrome, which has been reported with low-dose atypical antipsychotics used for treating insomnia, limits their use for PTSD-related nightmares.

Mr. S, a 45-year-old veteran, was diagnosed with posttraumatic stress disorder (PTSD) 18 years ago after a tour of duty in the Persian Gulf. He had combat-related flashbacks triggered by the smell of gasoline or smoke from a fire, was easily startled, and began to isolate himself socially. However, his symptoms improved when he started volunteering at his local Veterans Affairs Medical Center. After he lost his job 3 years ago, Mr. S started experiencing flashbacks. He was irritable, easily startled, and avoided things that reminded him of his time in the Persian Gulf. His psychiatrist prescribed sertraline, titrated to 200 mg/d. The drug reduced the severity of his avoidance and hyperarousal symptoms and improved his mood.

During a clinic visit, Mr. S says he is doing well and can fall asleep at night but is having recurring nightmares about traumatic events that occurred during combat. These nightmares wake him up and have become more frequent, occurring once per night for the past month. Mr. S says he has been watching more news programs about conflicts in Afghanistan and Iraq since the nightmares began. His psychiatrist starts quetiapine, 50 mg at bedtime for 7 nights then 100 mg at bedtime, but after 6 weeks Mr. S says his nightmares continue.

PTSD occurs in approximately 19% of Vietnam war combat veterans¹ and 14% of service members returning from Iraq and Afghanistan.² PTSD symptoms are classified into clusters: intrusive/re-experiencing; avoidant/numbing; and hyperarousal.³ Nightmares are part of the intrusive/re-experiencing cluster, which is Criterion B in DSM-IV-TR. See Table 1 for a description of DSM-IV-TR PTSD criteria. Among PTSD patients, 50% to 70% report PTSD-associated nightmares.⁴ Despite adequate treatment targeted to improve PTSD’s core symptoms, symptoms such as sleep disturbances or nightmares often persist.

Table 1

DSM-IV-TR diagnostic criteria for posttraumatic stress disorder

The person has been exposed to a traumatic event in which both of the following were present: The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others The person’s response involved intense fear, helplessness, or horror The traumatic event is persistently reexperienced in ≥1 of the following ways: Recurrent and intrusive distressing recollections of the event Recurrent distressing dreams of the event Acting or feeling as if the traumatic event were recurring Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event Physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by ≥3 of the following: Efforts to avoid thoughts, feelings, or conversations associated with the trauma Efforts to avoid activities, places, or people that arouse recollections of the trauma Inability to recall an important aspect of the trauma Markedly diminished interest or participation in significant activities Feeling of detachment or estrangement from others Restricted range of affect Sense of a foreshortened future Persistent symptoms of increased arousal (not present before the trauma), as indicated by ≥2 of the following: Difficulty falling or staying asleep Irritability or outbursts of anger Difficulty concentrating Hypervigilance Exaggerated startle response Duration of disturbance (symptoms in Criteria B, C, and D) is >1 month The disturbance causes clinically significant distress or impairment of social, occupational, or other important areas of functioning
Source: Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

The person has been exposed to a traumatic event in which both of the following were present:
1. The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others
2. The person’s response involved intense fear, helplessness, or horror
The traumatic event is persistently reexperienced in ≥1 of the following ways:
1. Recurrent and intrusive distressing recollections of the event
2. Recurrent distressing dreams of the event
3. Acting or feeling as if the traumatic event were recurring
4. Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event
5. Physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event
Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by ≥3 of the following:
1. Efforts to avoid thoughts, feelings, or conversations associated with the trauma
2. Efforts to avoid activities, places, or people that arouse recollections of the trauma
3. Inability to recall an important aspect of the trauma
4. Markedly diminished interest or participation in significant activities
5. Feeling of detachment or estrangement from others
6. Restricted range of affect
7. Sense of a foreshortened future
Persistent symptoms of increased arousal (not present before the trauma), as indicated by ≥2 of the following:
1. Difficulty falling or staying asleep
2. Irritability or outbursts of anger
3. Difficulty concentrating
4. Hypervigilance
5. Exaggerated startle response
Duration of disturbance (symptoms in Criteria B, C, and D) is >1 month
The disturbance causes clinically significant distress or impairment of social, occupational, or other important areas of functioning

Source: Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000

Nightmares and other sleep disturbances are associated with significant distress and daytime impairment and can interfere with PTSD recovery^4-8 by disrupting sleep-dependent processing of emotional experiences and causing repeated resensitization to trauma cues (Table 2).⁸

Table 2

Psychosocial consequences of sleep disruption in PTSD

Increased reactivity to emotional cues
Compromised ability to function in social and occupational roles
Negative psychiatric outcomes, including suicidal ideation or worsening of depression or psychosis
Interference of natural recovery from trauma exposure
Repeated resensitization to trauma cues
Neurocognitive deficits
Neuroendocrine abnormalities
PTSD: posttraumatic stress disorder Source: Adapted from reference 8

Few randomized controlled medication trials specifically address PTSD-related nightmares. Most PTSD studies do not examine sleep outcomes as a primary measure, and comprehensive literature reviews could not offer evidence-based recommendations.^9,10 The American Academy of Sleep Medicine (AASM) also noted a paucity of PTSD studies that identified nightmares as a primary outcome measure.¹¹ See Table 3 for a list of recommended medication options for PTSD-associated nightmares.