Concurrent psychiatric illness in non-Hispanic outpatients diagnosed as having posttraumatic stress disorder

Twenty-five consecutive admissions to an outpatient group therapy program for combat veterans meeting DSM-III criteria for posttraumatic stress disorder were systematically screened using operational diagnostic criteria for other coexisting psychiatric conditions, past or present. Eighty-four percent had coexisting conditions which, with one exception, were not significantly different in prevalence from those of an inpatient sample of combat veterans previously reported by the authors. The exception was a lower frequency of drug dependence in the outpatients compared with the inpatients. The authors conclude that a high proportion of conditions and symptoms--particularly alcoholism, antisocial personality, drug abuse, depression, and anxiety--can be routinely expected to coexist with posttraumatic stress disorder when it is diagnosed in Vietnam combat veterans.     

Urinary free-cortisol levels in posttraumatic stress disorder patients

Urinary free-cortisol levels (micrograms per day) were measured by radioimmunoassay at 2-week intervals during the course of hospitalization in the following patient groups: posttraumatic stress disorder (PTSD); major depressive disorder; bipolar I, manic; paranoid schizophrenia; and undifferentiated schizophrenia. The mean cortisol level during hospitalization was significantly lower in PTSD (33.3 +/- 3.2) than in major depressive disorder (49.6 +/- 5.9), bipolar I, manic (62.7 +/- 6.7), and undifferentiated schizophrenia (50.1 +/- 8.9), but was similar to that in paranoid schizophrenia (37.5 +/- 3.9). The same differences across groups are evident in the first sample following hospital admission. This finding of low, stable cortisol levels in PTSD patients is especially noteworthy, first because of the overt signs of anxiety and depression, which would usually be expected to accompany cortisol elevations, and second because of the concomitant chronic increase in sympathetic nervous system activity shown in prior psychophysiological studies of PTSD and reflected in marked and sustained urinary catecholamine elevations previously reported in our own PTSD sample. The findings suggest a possible role of defensive organization as a basis for the low, constricted cortisol levels in PTSD and paranoid schizophrenic patients. The data also suggest the possible usefulness of hormonal criteria as an adjunct to the clinical diagnosis of PTSD.     

Nefazodone in patients with treatment-refractory posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic disorder among combat veterans, persisting in as many as 15% of Vietnam veterans for at least 20 years. Treatment response in veterans with combat-related PTSD has been disappointing. Although anxiolytics, anticonvulsants, antipsychotics, and antidepressants have been tried, none has been consistently associated with improvement in all primary symptom domains (i.e., intrusive recollections, avoidance/numbing, and hyperarousal). This open-label study evaluated the use of nefazodone in a group of Vietnam veterans with chronic, treatment-refractory symptoms of PTSD. METHOD: Male outpatients with DSM-IV PTSD who had failed a minimum of 3 previous medication trials were eligible for the study. Nineteen Vietnam combat veterans entered the study and were treated with nefazodone, 100-600 mg/day, for 12 weeks. PTSD symptoms, anxiety, depression, sleep, sexual functioning, and adverse events were assessed weekly. RESULTS: Severity of depression lessened, as did PTSD symptoms of intrusive recollections, avoidance, and hyperarousal. Depressive symptom severity as measured by the Beck Depression Inventory decreased by a mean of 30%. Similarly, there was an overall drop in the intensity of PTSD symptoms as measured by the Clinician Administered PTSD Scale of 32% with a 26% improvement for symptoms of intrusion, 33% for avoidance, and 28% for arousal. In addition, improvements in sleep and sexual functioning were reported. The mean daily dose of nefazodone after 12 weeks was 430 mg (range, 200-600 mg/day). The most frequently reported side effects were headaches (53%), dry mouth (42%), and diarrhea (42%), but side effects tended to be mild and transient. CONCLUSION: In this group of Vietnam veterans with chronic treatment-refractory PTSD and multiple comorbid Axis I psychiatric disorders, nefazodone was well tolerated and effective. Larger, controlled studies are warranted.     

Clonidine in Cambodian patients with posttraumatic stress disorder

Some symptoms of posttraumatic stress disorder (PTSD) are related to central nervous system adrenergic hyperarousal. It has been suggested that an adrenergic receptor-blocker could be used to diminish, if not alleviate, the target symptoms of PTSD. Severely traumatized Cambodian refugee patients (N = 68) who suffered from chronic PTSD and major depression improved symptomatically when treated with a combination of clonidine and imipramine. A prospective pilot study of nine patients using this combination of an alpha-2 adrenergic agonist and a tricyclic antidepressant resulted in improved symptoms of depression in six patients, five to the point that DSM-III-R diagnoses were no longer met. The average decrease in the Hamilton Rating Scale for Depression score was 16. PTSD global symptoms improved in six patients but only in two to the point that DSM-III-R diagnoses were not met. There was no further sleep disorder in five and the frequency of nightmares lessened in seven patients. Startle reaction improved only in four patients; avoidance behavior showed little improvement in any of the nine. The imipramine-clonidine combination was well tolerated and presents a promising treatment for severely depressed and traumatized patients, although further studies are needed.     

Chronicity in posttraumatic stress disorder and predictors of the course of posttraumatic stress disorder among primary care patients

The present study examined the course of posttraumatic stress disorder (PTSD) in a sample of 84 primary care patients. More specifically, this study investigated the role of Axis I comorbidity, psychosocial impairment, and treatment participation in the maintenance of an episode of chronic PTSD and whether patients at follow-up met criteria for PTSD (full remission) or continued to exhibit residual PTSD symptoms and impairment (partial PTSD). Diagnostic structured interviews established all clinical diagnoses and information on the course of anxiety disorder symptoms, psychosocial functioning, and treatment status. Using a prospective, longitudinal design, this study found that during the first 2 years of follow-up, the probability of no longer meeting full DSM-IV criteria for PTSD was .69, and .18 for full remission from PTSD. The number of comorbid anxiety disorders and degree of psychosocial impairment at intake were significantly related to remission status (i.e., full and partial PTSD). This study suggests that, in a primary care setting, PTSD is a persistent illness, and that many subjects who have recovered from PTSD continue to suffer from subthreshold symptoms of PTSD.     

Mineralocorticoid receptor function in patients with posttraumatic stress disorder

OBJECTIVE: The study examined whether enhanced limbic mineralocorticoid receptor activity resulting in negative glucocorticoid feedback could contribute to the diminished basal and stress-induced cortisol output reported in patients with posttraumatic stress disorder (PTSD). METHOD: The effects of acute antimineralocorticoid (spironolactone) versus placebo pretreatment on levels of plasma cortisol at baseline and after stimulations with corticotropin-releasing hormone (CRH) and on adrenocorticotropic hormone (ACTH) level were measured in 12 PTSD patients and 12 healthy comparison subjects. RESULTS: Spironolactone significantly elevated basal cortisol and ACTH concentrations as well as cortisol secretion after CRH stimulation, but no differential effect between PTSD patients and comparison subjects was detected. CONCLUSIONS: The results indicate intact, but not enhanced, mineralocorticoid receptor function in PTSD. The study's experimental conditions did not allow determination of whether other compensatory factors might have masked the putative mineralocorticoid receptor changes.     

Rumination in posttraumatic stress disorder

Recent studies have shown that rumination is a powerful predictor of persistent posttraumatic stress disorder (PTSD). However, to date, the mechanisms by which rumination maintains PTSD symptoms are little understood. Two studies of assault survivors, a cross-sectional (N = 81) and a 6-month prospective longitudinal study (N = 73), examined several facets of ruminative thinking to establish which aspects of rumination provide the link to PTSD. The current investigation showed that rumination is not only used as a strategy to cope with intrusive memories but it also triggers such memories. Certain characteristics of rumination, such as compulsion to continue ruminating, occurrence of unproductive thoughts, and "why" and "what if" type questions, as well as negative emotions before and after rumination, were significantly associated with PTSD, concurrently and prospectively. These characteristics explained significantly more variance in PTSD severity than the mere presence of rumination, thereby indicating that not all ways of ruminative thinking are equally maladaptive.     

Persistent posttraumatic stress disorder following September 11 in patients with bipolar disorder

OBJECTIVE: We examined the development of posttraumatic stress disorder (PTSD) following indirect exposure to the September 11, 2001, terrorist attacks in a cohort at high risk for adverse trauma-related sequelae as a result of having bipolar disorder. METHOD: Subjects (N = 137) were participants in the ongoing, naturalistic, longitudinal study Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) prior to September 11, 2001. The present study examined prospectively collected pre-event information about bipolar disorder and other potential predictors of PTSD, along with assessment of the level of indirect trauma exposure (i.e., via media) and peritraumatic distress in the aftermath of September 11, and their association with 9/11-related, new-onset PTSD as assessed by a self-report measure, the Posttraumatic Stress Diagnostic Scale. RESULTS: Posttrauma assessments were completed a mean +/- SD of 430.6 +/- 78.7 days (range, 0.5-1.5 years) after September 11. Twenty percent (N = 27) of patients reported development of new-onset PTSD in response to the September 11 attacks. Rates of PTSD were significantly associated with the presence of a hypomanic, manic, or mixed mood state at the time of trauma (chi(2) = 4.25; p < .05); 62% of patients in these states developed PTSD. Mania/hypomania remained a significant predictor of PTSD in response to the September 11 attacks after controlling for peritraumatic exposure and distress variables, suggestive of a substantial increase in risk compared with those in recovery (OR = 17; 95% CI = 2.6 to 115.6; p = .0034). CONCLUSIONS: Rates of persistent new-onset PTSD among bipolar patients were elevated in the aftermath of the September 11 attacks. Our findings suggest that the presence of a manic state may be the most critical risk factor for adverse sequelae following indirect traumatic exposure in bipolar individuals.     

The corticotropin-releasing hormone test in patients with posttraumatic stress disorder

To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.     

Predictors of treatment response in patients with posttraumatic stress disorder

1. This study examines the relation between baseline clinical characteristics in patients with posttraumatic stress disorder (PTSD) and response to treatment with a reversible monoamine oxidase A inhibitor (RIMA), brofaromine. 2. Data from two comparable, double-blind, placebo-controlled studies of brofaromine in patients with PTSD were combined. Bivariate analyses of variables of interest and outcome were performed. 3. Treatment response was significantly associated with lower baseline scores on the full scale Clinician-Administered PTSD Scale (CAPS) and on CAPS subscales B (re-experiencing) and C (avoidance/numbing), as well as to drug treatment with brofaromine. Placebo response was related to a history of past sexual trauma. 4. Brofaromine may have therapeutic benefit in treating PTSD, with lower baseline levels of reexperiencing and avoidance/numbing and overall less severe PTSD most predictive of outcome.     

Antiepileptic drugs in posttraumatic stress disorder

Antiepileptic drugs might be effective in the treatment of patients with Posttraumatic Stress Disorder, a condition with unmet pharmacologic needs. We review the literature on the efficacy and tolerability of antiepileptic drugs in Posttraumatic Stress Disorder, both case reports and open studies, as well as controlled studies if available. The results of the studies will be presented together with their methodological limitations (e.g., open trials, use of additional medications, and lack of use of standardized scales for Posttraumatic Stress Disorder). The effects of antiepileptic drugs on kindling, a suggested pathogenesis for Posttraumatic Stress Disorder are overviewed, and suggestions for further research are raised.     

Low urinary cortisol excretion in patients with posttraumatic stress disorder

In the present study, we replicated and extended our previous findings of low urinary free-cortisol levels in PTSD. Cortisol was measured in 16 male patients (nine inpatients, seven outpatients) with posttraumatic stress disorder (PTSD) and in 16 nonpsychiatric control subjects. The mean cortisol level in the PTSD group was significantly lower, and the range narrower, than that observed in control subjects. Low cortisol in PTSD did not seem to be related to the presence or absence of major depressive disorder or to overall psychiatric symptomatology as assessed by the sum Brief Psychiatric Rating Scale score. In the outpatient group, there was a relationship between PTSD symptomatology and cortisol levels. The findings suggests a physiological adaptation of the hypothalamic-pituitary-adrenal axis to chronic stress.     

Plasma testosterone levels in patients with combat-related posttraumatic stress disorder

BACKGROUND: An abnormal level of androgens has been reported in various psychiatric disorders and the important role of androgens in the regulation of human sexuality, aggression, cognition, emotions and personality have been described. Previous studies in the area of stress and the hypothalamic-pituitary-gonadal (HPG) system in humans indicate that circulating testosterone levels are suppressed by physical and psychological stress. However, there is also evidence that plasma levels of testosterone can increase during potentially stressful events and may be elevated in combat-related posttraumatic stress disorder (CR-PTSD) in comparison with normal subjects and major depressive disorder patients. METHODS: The aim of the present study was to examine the possible involvement of the HPG system in chronic untreated CR-PTSD. To this end, we assessed the morning plasma levels of testosterone and cortisol in never-treated chronic CR-PTSD outpatients compared with normal healthy controls. RESULTS: There were no statistically significant differences between the CR-PTSD patients and healthy control subjects in morning plasma testosterone (547.8 +/- 152.2 ng/dl vs. 565.6 +/- 122.4 ng/dl; p = 0.7) and cortisol (19.0 +/- 8.5 microg/dl vs. 15.4 +/- 5.1 microg/dl; p = 0.1) levels. However, a significant correlation between plasma testosterone level and avoidance symptom scores of the Impact of Events Scale (IES) was found in the CR-PTSD patients (r = 0.43, p < 0.05). CONCLUSIONS: The findings of plasma testosterone levels comparable with normal controls in CR-PTSD patients may indicate that the previously described reduction in testosterone levels in normal subjects under stressful conditions may reflect the acute stress response of the HPG axis, in contrast to an adaptation of the HPG axis under chronic psychological stress.