Levetiracetam for treatment-refractory posttraumatic stress disorder

OBJECTIVE: To assess the use of levetiracetam, a novel anticonvulsant agent, in the treatment of refractory posttraumatic stress disorder (PTSD). METHOD: Retrospective analysis was conducted of 23 patients with DSM-IV diagnosis of PTSD who, after being deemed partial or nonresponders to antidepressant therapy, received levetiracetam in a naturalistic fashion. The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). Secondary outcome measures included the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I). RESULTS: Levetiracetam at a mean+/-SD dose of 1967+/-650 mg/day for 9.7+/-3.7 weeks was generally well tolerated. Nineteen patients (83%) were taking at least 1 concomitant medication. Patients were severely ill with a mean baseline PCL-C score of 67.2+/-9.4, CGI-S score of 6.0+/-0.7, and HAM-A score of 26.8+/-4.9. Patients improved significantly on all measures (p<.001). Thirteen patients (56%) met responder criteria at endpoint (PCL-C mean change=23.5, CGI-I score相似文献   

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.     

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.     

Concurrent posttraumatic stress disorder in psychogeriatric patients

Despite the fact that there are over 11 million World War II veterans in the United States, recent research on combat-related trauma has focused primarily on symptoms of posttraumatic stress disorder (PTSD) in Vietnam veterans. Several studies have found that the majority of Vietnam veterans who meet the Diagnostic and Statistical Manual of Mental Disorders, ed 3 (DSM-III) criteria for PTSD have an additional major psychiatric diagnosis. This study explores the presence of the diagnosis of PTSD in an inpatient sample of 42 World War II veterans with an admission diagnosis other than PTSD. Following a structured diagnostic interview, a second examiner, blind to the patients' combat history, interviewed the subjects to obtain information regarding the past and current impact of the "most stressful experience" of their lives. Subjects were instructed not to reveal the nature of the stressor until completion of the study. Fifty-four percent of the combat-exposed veterans (14 of 26) spontaneously listed combat as the most significant stressor in their life. Furthermore, 54% of the combat-exposed veterans met DSM-III criteria for past PTSD and 27% met criteria for current PTSD in addition to another axis I diagnosis. These preliminary findings underscore the need for clinicians to assess the long-term effects of combat trauma in psychogeriatric patients.     

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.     

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.     

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.     

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.     

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.     

Hippocampal function during associative learning in patients with posttraumatic stress disorder

In the last decade several studies have shown memory deficits in patients with posttraumatic stress disorder (PTSD) which have been associated with a reduced hippocampus volume. However, until now we do not know how or whether these structural abnormalities turn into functional abnormalities. Thus, the primary purpose of the present study was the investigation of the hippocampal function using functional magnet resonance imaging (fMRI).We compared PTSD patients and healthy control participants using an associative learning paradigm consisting of two encoding and one retrieval condition. During fMRI scanning participants had to learn face-profession pairs. Afterwards only faces were presented as cue stimuli for associating the category of the prior learned target profession and the participants had to decide whether this face belonged to a scientific or an artistic profession. Additionally, cognitive functioning, i.e. memory and attention, was examined using neuropsychological standard tests.During encoding PTSD patients showed stronger hippocampal and weaker prefrontal activation compared to healthy control participants. During retrieval the two groups did not differ neither in hippocampus activation nor in accuracy of retrieval. PTSD patients however showed a reduced activation in the left parahippocampal gyrus and other memory-related brain regions. We did not find any significant memory differences between PTSD patients and healthy control participants.The results suggest that PTSD has an effect on memory-related brain function despite intact memory functioning. In particular the hippocampal/parahippocampal regions and the prefrontal cortex show functional alterations during associative learning and memory.     

Sleep findings in young adult patients with posttraumatic stress disorder.

BACKGROUND: Laboratory sleep studies in posttraumatic stress disorder (PTSD) have not provided consistent evidence of sleep disturbance, despite apparent sleep complaints. Most of these studies have investigated middle-aged chronic PTSD subjects with a high prevalence of comorbidities such as substance dependence and/or personality disorder. METHODS: Ten young adult PTSD patients (aged 23.4 +/- 6.1 years) without comorbidities of substance dependence and/or personality disorder underwent 2-night polysomnographic recordings. These sleep measures were compared with those of normal control subjects and were correlated with PTSD symptoms. RESULTS: Posttraumatic stress disorder patients demonstrated significantly poorer sleep, reduced sleep efficiency caused by increased wake time after sleep onset, and increased awakening from rapid eye movement (REM) sleep (REM interruption). We found significant positive correlations between the severity of trauma-related nightmare complaints and the percentage of REM interruption, as well as wake time after sleep onset. CONCLUSIONS: The results indicate that trauma-related nightmares are an important factor resulting in increased REM interruptions and wake time after sleep onset in PTSD.     

Dimensional complexity of the EEG in patients with posttraumatic stress disorder

Recent electrophysiological studies have reported evidence of information processing abnormalities in patients with posttraumatic stress disorder (PTSD). The aim of this study is to examine dynamical complexity of the EEG in PTSD patients, which is thought to reflect information processing of the brain. Resting EEG recordings (32,800 data points acquired continuously from 82 s of an EEG record) were obtained in 16 channels of 27 patients with PTSD from a mixed civilian trauma population and 14 healthy subjects. The correlation dimension (D2) of the EEG was used to quantify the complexity of the cortical dynamics underlying the EEG signal. The PTSD patients were found to have lower D2 values than those of the healthy subjects in most channels (Fp1, F8, C4, P4, T3, T4, T5, T6, and O1), indicating that PTSD patients have globally reduced complexity in their EEG waveforms. This study supports the hypotheses that PTSD patients exhibit disturbed cortical information processing, and that non-linear dynamical analysis of the EEG can be a tool for detecting changes in neurodynamics of the brain in PTSD.     

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.