Miles E. McFall

A Parallel Group Placebo Controlled Study of Prazosin for Trauma Nightmares and Sleep Disturbance in Combat Veterans with Post-Traumatic Stress Disorder

BACKGROUNDnExcessive brain responsiveness to norepinephrine appears to contribute to post-traumatic stress disorder (PTSD), particularly at night. Prazosin, a brain active alpha-1 adrenergic receptor antagonist, significantly reduced trauma nightmares and sleep disturbance in 10 Vietnam War combat veterans in a previous placebo-controlled crossover study. The current parallel group trial in a larger sample of veterans evaluated prazosin effects on trauma nightmares, sleep quality, global clinical status, dream characteristics, and comorbid depression.nnnMETHODSnForty veterans (mean age 56 +/- 9) with chronic PTSD and distressing trauma nightmares and sleep disturbance were randomized to evening prazosin (13.3 +/- 3 mg/day) or placebo for 8 weeks.nnnRESULTSnIn the evaluable sample (n = 34), primary outcome measures demonstrated that prazosin was significantly superior to placebo for reducing trauma nightmares and improving sleep quality and global clinical status with large effect sizes. Prazosin shifted dream characteristics from those typical of trauma-related nightmares toward those typical of normal dreams. Blood pressure changes from baseline to end study did not differ significantly between prazosin and placebo.nnnCONCLUSIONSnPrazosin is an effective and well-tolerated treatment for trauma nightmares, sleep disturbance and global clinical status in veterans with chronic PTSD.

Posttraumatic Stress Disorder as a Risk Factor for Suicidal Ideation in Iraq and Afghanistan War Veterans

Posttraumatic stress disorder (PTSD) was examined as a risk factor for suicidal ideation in Iraq and Afghanistan War veterans (N = 407) referred to Veterans Affairs mental health care. The authors also examined if risk for suicidal ideation was increased by the presence of comorbid mental disorders in veterans with PTSD. Veterans who screened positive for PTSD were more than 4 times as likely to endorse suicidal ideation relative to non-PTSD veterans. Among veterans who screened positive for PTSD (n = 202), the risk for suicidal ideation was 5.7 times greater in veterans who screened positive for two or more comorbid disorders relative to veterans with PTSD only. Findings are relevant to identifying risk for suicide behaviors in Iraq and Afghanistan War veterans.

Autonomic responses to stress in Vietnam combat veterans with posttraumatic stress disorder

This study tested the hypothesis that combat veterans with posttraumatic stress disorder (PTSD) experience sympathetic nervous system activation in response to war-related laboratory stimuli. Circulating plasma catecholamines, vital signs, and affect ratings were measured in 10 Vietnam combat veterans with PTSD and 11 control subjects, during and after viewing combat and noncombat stress films. PTSD subjects responded more strongly than controls to the combat film, with greater increases in plasma epinephrine, pulse, blood pressure, and subjective distress. The increases in autonomic activity of PTSD subjects was more pronounced and long lasting in response to the combat film than to the noncombat film, but type of film had no systematic effect on control subjects responses. These findings are consistent with biological models that posit sympathoadrenal activation in response to memory-evoking cues of traumatic events in PTSD.

Glucocorticoid feedback sensitivity and adrenocortical responsiveness in posttraumatic stress disorder

BACKGROUNDnDecreased basal cortisol levels have been reported in individuals with posttraumatic stress disorder (PTSD). There is evidence for enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, which could account for this, but other possible mechanisms have not been ruled out. We examined the HPA axis employing a metyrapone-cortisol infusion protocol designed to study negative feedback sensitivity.nnnMETHODSnVietnam combat trauma-exposed subjects met DSM-IV criteria for PTSD. Exclusion criteria included substance abuse and most medications. Endogenous feedback inhibition was removed by blocking cortisol synthesis with oral metyrapone and reintroduced by intravenous infusion of cortisol. In a placebo condition, subjects received oral placebo and normal saline infusion. Serial blood samples drawn over 4 hours were assayed for adrenocorticotrophic hormone (ACTH), cortisol, and 11-deoxycortisol. Selected samples were assayed for cortisol binding globulin (CBG) and dehydroepiandrosterone (DHEA).nnnRESULTSnBasal plasma cortisol was significantly decreased in PTSD subjects (n = 13) compared with control subjects (n = 16). No significant difference in the ACTH response to cortisol infusion following metyrapone was observed; however 11-deoxycortisol was significantly decreased in PTSD subjects. In addition, CBG was significantly increased in PTSD subjects, and DHEA was significantly decreased in both PTSD and combat-exposed control subjects.nnnCONCLUSIONSnThese observations suggest decreased adrenocortical responsiveness may be an additional or alternative mechanism accounting for low cortisol in PTSD.

Basal sympathoadrenal function in posttraumatic distress disorder

Research has consistently shown that patients with posttraumatic stress disorder (PTSD) manifest greater changes in heart rate, blood pressure, and plasma epinephrine than controls when exposed to trauma-related laboratory stressors. However, findings are equivocal as to whether PTSD subjects differ from controls on basal, or tonic, measures of autonomic activity. In this study, PTSD patients (n = 11) and asymptomatic controls (n = 11) were compared on measures of basal sympathoadrenal function, including plasma norepinephrine and epinephrine as well as heart rate and blood pressure. Results showed that PTSD patients were not significantly different from control subjects on any measure. Although phasic alterations in autonomic function in PTSD have been consistently found in previous research, this study suggests that tonic sympathetic nervous system activity in PTSD patients may not differ from that of healthy controls.

Plasma norepinephrine kinetics in patients with posttraumatic stress disorder

To determine whether basal sympathetic nervous system (SNS) function is increased in patients with posttraumatic stress disorder (PTSD), we used a radioisotope dilution technique to assess basal arterialized plasma norepinephrine (NE) kinetics in 12 men who were Viet Nam combat veterans with PTSD and six normal controls. In addition to determining the rates of appearance of NE into, and clearance of NE from, plasma, we measured basal arterialized plasma levels of epinephrine (EPI), and also vital signs, in both groups. Patients with PTSD actually manifested lower arterialized plasma levels of NE, and had lower rates of appearance of NE into plasma, than did controls. The rate of NE clearance from plasma was unaltered in PTSD patients. Patients with PTSD also showed a trend toward lower arterialized EPI levels than controls, but manifested a trend toward higher diastolic blood pressure. Our data indicate that basal SNS activity is not increased in patients with PTSD and that previous reports of increased resting SNS activity in this population may instead reflect SNS reactivity.

Nonnightmare distressed awakenings in veterans with posttraumatic stress disorder: Response to prazosin†

Twenty-two veterans with posttraumatic stress disorder (PTSD) were assessed for trauma-related nightmares and nonnightmare distressed awakenings (NNDA) before and after treatment with the alpha-1 adrenoreceptor antagonist prazosin at an average bedtime dose of 9.6 mg/day. Ratings combining frequency and intensity dimensions of trauma-related nightmares decreased from 3.6 to 2.2, NNDA from 5.2 to 2.1, and sleep difficulty from 7.2 to 4.1 per week. These results suggest that increased brain adrenergic activity may contribute to the pathophysiology of both trauma-related nightmares and NNDA in PTSD.

Combat-related PTSD and psychosocial adjustment problems among substance abusing veterans

The purposes of this study were the following: a) to determine the prevalence of combatrelated posttraumatic stress disorder (PTSD) symptoms among veterans seeking assistance at a Veterans Administration medical center substance abuse treatment facility, b) to examine the relative contribution of Vietnam war zone variables to PTSD symptom development, and c) to study psychosocial adjustment problems associated with Vietnam combat exposure and with PTSD symptoms among help-seeking substance abusing men. Of 489 male veterans presenting for treatment, 10.7% had significant Vietnam combat-related PTSD symptoms as measured by the Mississippi Scale for Combat-Related PTSD. Clinically significant PTSD symptoms occurred among 46% of the subsample of combat-exposed Vietnam veterans with substance abuse problems. Degree of combat exposure was the most important military stressor that distinguished Vietnam veterans with PTSD from those without PTSD, but the groups also differed on age of war zone duty, duration of war zone duty, and whether they were wounded. Veterans who served in Vietnam did not differ from veterans who had no war zone duty on various parameters of psychosocial adjustment. However, the subgroup of Vietnam veterans with PTSD symptoms reported significantly greater psychosocial adjustment problems than their counterparts who did not have PTSD. The deleterious effects associated with combat-related PTSD appeared to be confined to adjunctive psychiatric difficulties and unemployment and did not increase risk of arrests for antisocial conduct beyond that found for veterans without PTSD. Methodological and clinical implications of these findings are discussed.

Multidimensional assessment of anger in Vietnam veterans with posttraumatic stress disorder

This study examined the effects of combat exposure and posttraumatic stress disorder (PTSD) on dimensions of anger in Vietnam veterans. Vietnam combat veterans were compared with Vietnam era veterans without war zone duty on the Multidimensional Anger Inventory (MAI). Combat veterans were not significantly more angry than their veteran peers who did not serve in Southeast Asia. Additionally, various parameters of war zone duty were not highly associated with anger scores. However, combat veterans with PTSD scored significantly higher than veterans without PTSD on measures of anger arousal, range of anger-eliciting situations, hostile attitudinal outlook, and tendency to hold anger in. These results suggest that PTSD, rather than war zone duty, is associated with various dimensions of angry affect.

Risk of misinterpretation of MMPI Schizophrenia scale elevations in chronic pain patients

&NA; Seventy‐three chronic pain patients with elevated MMPI Schizophrenia (Sc) scale scores (T score > 70) were compared with 55 psychotic and 87 non‐psychotic psychiatric patients with elevated Sc scores to examine group differences in item content patterns on the Harris and Lingoes subscales. Chronic pain patients evidenced lower scores on all Harris and Lingoes Sc subscales, except for the Bizarre Sensory Experiences subscale on which they scored significantly higher than the psychiatric groups. Results demonstrate that Sc is elevated in many chronic pain patients because they endorse somatic symptoms and items suggestive of depression and inertia, whereas psychotics endorse more items reflecting bizarre and disordered thinking, social alienation and defective inhibition, and non‐psychotic psychiatric patients endorse more depression, despair, thought disorganization and social alienation. These data suggest that high Sc scores of many chronic pain patients reflect symptoms and sequelae of their physical problems, and do not necessarily reflect severe psychopathology.