Treatment of sleep disturbances in posttraumatic stress disorder: a review.

Sleep disturbances are among the most commonly reported posttraumatic stress disorder (PTSD) symptoms. It is essential to conduct a careful assessment of the presenting sleep disturbance to select the optimal available treatment. Cognitive-behavioral therapies (CBTs) are at least as effective as pharmacologic treatment in the short-term and more enduring in their beneficial effects. Cognitive-behavioral treatment for insomnia and imagery rehearsal therapy have been developed to specifically treat insomnia and nightmares and offer promise for more effective relief of these very distressing symptoms. Pharmacotherapy continues to be an important treatment choice for PTSD sleep disturbances as an adjunct to CBT, when CBT is ineffective or not available, or when the patient declines CBT. Great need exists for more investigation into the effectiveness of specific pharmacologic agents for PTSD sleep disturbances and the dissemination of the findings to prescribers. The studies of prazosin and the findings of its effectiveness for PTSD sleep disturbance are examples of studies of pharmacologic agents needed in this area. Despite the progress made in developing more specific treatments for sleep disturbances in PTSD, insomnia and nightmares may not fully resolve.

No improvement of posttraumatic stress disorder symptoms with guanfacine treatment.

OBJECTIVE: The authors report an 8-week, double-blind, randomized controlled trial of guanfacine versus placebo for posttraumatic stress disorder (PTSD). METHOD: Veterans with chronic PTSD who were medication-free or receiving stable pharmacotherapy were randomly assigned to guanfacine (N=29) versus placebo (N=34). RESULTS: Guanfacine had no effect on PTSD symptoms, subjective sleep quality, or general mood disturbances. Guanfacine was associated with a number of side effects. CONCLUSIONS: These results do not support the use of alpha 2 agonists in veterans with chronic PTSD.

Current concepts in pharmacotherapy for posttraumatic stress disorder.

OBJECTIVE: This article describes current approaches to the pharmacologic treatment of posttraumatic stress disorder (PTSD) and reviews the classes of pharmacologic agents used in the treatment of PTSD. Pharmacotherapy for PTSD that is comorbid with other psychiatric disorders is highlighted. METHODS: The primary-source literature was reviewed by using a MEDLINE search. Secondary-source review articles and chapters were also used. Results from studies of the psychophysiology of PTSD are outlined in the review to help inform treatment choices. The review gives more consideration to controlled studies than to open clinical trials. Recommendations for treatment are evidence based. RESULTS AND DISCUSSION: A growing body of evidence demonstrates the efficacy of pharmacologic treatment for PTSD. The effectiveness of the selective serotonin reuptake inhibitors sertraline and paroxetine in large-scale, well-designed, placebo-controlled trials resulted in their being the first medications to receive approval from the U.S. Food and Drug Administration for the treatment of PTSD. Observation of psychophysiologic alterations associated with PTSD has led to the study of adrenergic-inhibiting agents and mood stabilizers as therapeutic agents. Controlled clinical trials with these classes of medication are needed to determine their efficacy for treating PTSD. Finally, the choice of medication for treating PTSD is often determined by the prominence of specific PTSD symptoms and the pattern of comorbid psychiatric conditions.

Delta sleep response to metyrapone in post-traumatic stress disorder.

Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combat-related PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.

The effect of nefazodone on subjective and objective sleep quality in posttraumatic stress disorder.

BACKGROUND: This study assesses the efficacy of nefazodone treatment (target dose of 400-600 mg/day) on objective and subjective sleep quality in Vietnam combat veterans with chronic DSM-IV posttraumatic stress disorder (PTSD). METHOD: Medically healthy male Vietnam theater combat veterans with DSM-IV PTSD (N = 10) completed a 12-week open-label trial. Two nights of ambulatory polysomnography were obtained at baseline and at the end of the trial. PTSD and depressive symptoms and subjective sleep quality were assessed at baseline and after 12 weeks. Data were collected in 1999 and 2000. RESULTS: Nefazodone treatment led to a significant decrease in PTSD and depressive symptoms (p <.05), an improvement in global subjective sleep quality, and a reduction in nightmares. Nefazodone also resulted in a substantial improvement in objective measures of sleep quality, particularly increased total sleep time, sleep maintenance, and delta sleep as measured by period amplitude analysis. CONCLUSION: Nefazodone therapy results in an improvement of both subjective and objective sleep quality in subjects with combat-related PTSD.

Temporal instability of auditory and visual event-related potentials in posttraumatic stress disorder.

BACKGROUND: We examined P300 measures in patients with posttraumatic stress disorder (PTSD) and control subjects at two different time points to determine event-related potential (ERP) stability over time and the relationship of changes in ERPs to changes in symptom levels. METHODS: Auditory and visual P300 was recorded in a three-condition novelty oddball task in 25 male subjects with combat-related PTSD and 15 male combat-exposed normal control subjects at two time points separated by 6-12 months. Regression analyses were conducted to compare the temporal stability of ERP measures in PTSD and control subjects. Variability in ERP measures over time within PTSD subjects was examined for association with changes in symptom levels. RESULTS: There were no significant differences in P300 amplitude or latency in PTSD versus control subjects at either time point, regardless of stimulus type (target, novel) or modality (auditory, visual). Nine of 24 P300 measures were significantly less predictable over time in the PTSD group compared to control subjects. Variability of P300 measures over time was not associated with fluctuations in symptoms of depression or PTSD. CONCLUSIONS: P300 ERPs are more variable cross-sectionally and over time in PTSD subjects compared to trauma exposed control subjects. Measures of variability about the group mean appear to be more informative about the cognitive electrophysiology of PTSD than measures of central tendency.

New directions in the pharmacotherapy of posttraumatic stress disorder.

Advances in psychopharmacology of PTSD are presented, focusing on antidepressants, adrenergic agents, antianxiety agents, and mood stabilizers. Treatment recommendations are related to recent advances in the understanding of the biology of PTSD. Pharmacotherapy of PTSD in children and adolescents is discussed, including recommended dose ranges. Recommendations are specified for pharmacotherapy of trauma survivors in the immediate aftermath of traumatic exposure, and for those with acute and chronic posttraumatic stress disorders.