A non-randomized pilot trial of the use of prazosin in the prevention of transition from acute stress disorder to post-traumatic stress disorder.

BACKGROUND: Following a traumatic event, 40-80% of the patients with acute stress disorder (ASD) will develop post-traumatic stress disorder (PTSD), 67% at 6 months. Alpha1-blockers are effective in treating some symptoms of PTSD but their usefulness in acute stress situations remains unclear. We hypothesized that reducing noradrenergic hyperactivity with an alpha1-blocker during the acute phase after a traumatic event could prevent the transition to PTSD in patients with ASD. OBJECTIVE: To investigate the efficacy and safety of a 1-month course of alpha1-blocker (prazosin) to prevent the transition to PTSD in patients with ASD at 6 months. METHOD: In a monocentric open-label prospective pilot study, 15 patients with ASD were included within 3-7 days of exposure to a traumatic event. After enrolment, they received prazosin LP at home at bedtime at 2.5 mg/day for 7 days and then 5 mg/day for 21 days. Incidence of PTSD was assessed at 6 months using the Clinician Administrated PTSD Scale (CAPS). RESULTS: At 6 months, 22% of patients who completed the study (2/9) met the diagnostic criteria for PTSD. This rate was significantly lower than that observed in previous studies (67%; p = .047). The treatment was well tolerated and there were no serious adverse events. CONCLUSIONS: These preliminary findings indicating the safety of prazosin and suggesting its potential to prevent the development of PTSD in ASD require to be replicated in large-scale randomized placebo-controlled studies.Trial registration: The study was pre-registered on a public database (www.clinicalTrials.gov identifier: NCT03045016).

Alpha1-blockers are safe and well tolerated in patients with acute stress disorder.The use of alpha1-blockers 3­7 days after traumatic exposure is worthy of study.Alpha1-blockers could prevent the transition to PTSD in ASD patients at 6 months.

Mental Health in Elderly Spanish People in Times of COVID-19 Outbreak.

BACKGROUND: We aim to assess COVID-19 outbreak-related emotional symptoms, identify gender differences, and study the relationship between the emotional state and environmental features in the elderly. METHODS: We conducted a cross-sectional study starting on March 29 to April 5, 2020 based on a national online survey using snowball sampling techniques. Symptoms of anxiety (Hamilton Anxiety Scale), depression (Beck Depression Inventory) and acute stress (Acute Stress Disorder Inventory) were compared between people over and under 60 years old. Gender differences and the relationship of loneliness, regular exercise, economic losses and use of anxiolytics on the mental state were evaluated. RESULTS: One thousand six hundred thirty-nine (150 [9.2%] aged ≥60) participants completed the survey. The greater than or equal to 60 group showed lower mean (SD) BDI levels than the less than 60 group (3.02 [3.28] versus 4.30 [4.93]); and lower mean (SD) acute stress disorder inventory scores than the less than 60 group (3.68 [3.20] versus 4.45 [3.06]). There were no gender differences in any of the clinical measures. The presence of economic losses as well as the increase in the use of anxiolytics was significantly associated with higher emotional distress in the elderly compared to the younger group. CONCLUSIONS: Older people have shown less emotional distress, with no differences between men and women. Economic loss and substance use should be monitored to guarantee the emotional well-being of the elderly.

Clinical Use of Prazosin in a Patient With Acute Stress Disorder: A Case Report.

Prazosin is an alpha-1 blocker that is commonly given to patients with posttraumatic stress disorder (PTSD) to reduce nightmares and flashbacks. Its use in acute stress disorder (ASD), however, has not been well characterized. There is a moderately positive correlation between ASD and the subsequent development of PTSD, which indicates that there may be some common neurobiological mechanisms that connect the 2 conditions. We present the case of a 51-year-old man who was experiencing symptoms of ASD following a motor vehicle accident that occurred a few days earlier. He was reporting flashbacks and nightmares of the accident, but after being treated with prazosin, his symptoms completely resolved. Prazosin may be effective in treating the symptoms of ASD and, by doing this, it may also play a role in inhibiting the progression of ASD to PTSD.

Pharmacological prevention and early treatment of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is a common mental disorder associated with significant distress and reduced functioning. Its occurrence after a severe traumatic event and association with characteristic neurobiological changes make PTSD a good candidate for pharmacological prevention and early treatment. The primary aim for this systematic review and meta-analysis was to assess whether pharmacological interventions when compared to placebo, or other pharmacological/psychosocial interventions resulted in a clinically significant reduction or prevention of symptoms, improved functioning or quality of life, presence of disorder, or adverse effects. A systematic search was undertaken to identify RCTs, which used early pharmacotherapy (within three months of a traumatic event) to prevent and treat PTSD and acute stress disorder (ASD) in children and adults. Using Cochrane Collaboration methodology, RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD severity. 19 RCTs met the inclusion criteria; 16 studies with adult participants and three with children. The methodological quality of most trials was low. Only hydrocortisone in adults was found to be superior to placebo (3 studies, n = 88, RR: 0.21 (CI 0.05 to 0.89)) although this was in populations with severe physical illness, raising concerns about generalisability. No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate). Hydrocortisone shows the most promise, of pharmacotherapies subjected to RCTs, as an emerging intervention in the prevention of PTSD within three months after trauma and should be a target for further investigation. The limited evidence for hydrocortisone and its adverse effects mean it cannot be recommended for routine use, but, it could be considered as a preventative intervention for people with severe physical illness or injury, shortly after a traumatic event, as long as there are no contraindications. More research is needed using larger, high quality RCTs to establish the most efficacious use of hydrocortisone in different populations and optimal dosing, dosing window and route. There is currently a lack of evidence to suggest that other pharmacological agents are likely to be effective.

Topical fluorometholone treatment and desiccating stress change inflammatory protein expression in tears.

PURPOSE: It was hypothesized that tear protein biomarkers could predict the effects of topical steroid treatment and desiccating stress in patients with dry eye disease (DED). To test this concept, a randomized, double-masked, controlled clinical trial with 41 patients was conducted. METHODS: The patients were treated topically with either 0.1% fluorometholone (FML) or polyvinyl alcohol (PA). Tear samples were collected using 1 µl glass capillaries at recruitment into the study and after a 3-week treatment period, both before and after 2 h exposure to desiccating stress, in a controlled environment chamber. Relative quantification of tear proteins was conducted by NanoLC-MSTOF using sequential window acquisition of all theoretical mass spectra (SWATH). Ocular surface integrity (corneal and conjunctival staining and conjunctival hyperemia) was selected as the key DED-related sign and analyzed with proteomic data. Analysis of covariance (ANCOVA) and linear models were used to analyze the data with R. RESULTS: 758 proteins were identified and relatively quantified from each tear sample. Analysis revealed 9 differentially expressed proteins between FML and PA treatments after 3 weeks and 7 after desiccating stress (P < 0.05). We also identified several differentially expressed proteins at the initial collection, which could be used to predict changes of conjunctival and corneal staining and conjunctival hyperemia after FML treatment and after desiccating stress. These proteins include complement C3 (C3) and calmodulin like 5 (CALML5), which could also differentiate the severity of DED at baseline. CONCLUSIONS: The identified proteins could be further used as biomarkers to identify patients most benefiting from FML treatment.

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

PTSD treatment in light of DSM-5 and the "golden hours" concept.

One of the main changes in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was the separation of Stress Related Disorders from the Anxiety chapter. This separation paves the way to examine the unique characteristics of posttraumatic stress disorder (PTSD) (ie, identifiable onset, memory processes, etc) and related neural mechanisms. The time that elapses between the traumatic event and the manifestation of the disorder may also be addressed as the "golden hours," or the window of opportunity in which critical processes take place and relevant interventions may be administrated.

Evidence-based pharmacological treatment of generalized anxiety disorder.

Generalized anxiety disorder (GAD) is common in community and clinical settings. The associated individual and societal burden is substantial, but many of those who could benefit from treatment are not recognized or treated. This paper reviews the pharmacological treatment of GAD, based on findings of randomized placebo-controlled studies. Particular attention is paid to response rates to acute treatment, treatment tolerability, prediction of response, duration of treatment, and further management of patients who do not respond to initial treatment approaches. On the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials, recent evidence-based guidelines for pharmacological management have recommended initial treatment with either a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor, although there is also good evidence for the efficacy of pregabalin and quetiapine. It is difficult to predict reliably which patients will respond well to pharmacological treatment, but response to antidepressants is unlikely if there is no evidence of an onset of effect within 4 wk. The small number of placebo-controlled relapse-prevention studies causes uncertainty about the optimal duration of treatment after a satisfactory initial response, but continuing treatment for at least 12 months is recommended. There have been few investigations of the further management of patients who have not responded to first-line treatment, but switching to another evidence-based treatment, or augmentation approaches may be beneficial.

Posttraumatic stress disorder and stress-related disorders.

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder. Symptoms present shortly after an exposure to a traumatic event, abate with time in the majority of those who initially express them, and leave a significant minority with chronic PTSD. PTSD may be treated with pharmacotherapy or psychotherapy. Treatment of the early expressions of the disorder constitutes a separate domain of theory and research. Treatment of chronic PTSD often stabilizes the condition but rarely produces stable remission. This article reviews the empirical evidence on the treatment of acute and chronic PTSD, outlines similarities and differences between PTSD and other Axis I disorders, evaluates new therapeutic approaches, and discusses the implications of current knowledge for the forthcoming DSM-V.

Treating thermally injured children suffering symptoms of acute stress with imipramine and fluoxetine: a randomized, double-blind study.

INTRODUCTION: For pediatric burn patients with the symptoms of acute stress disorder (ASD) a first line medication is not widely agreed upon. A prospective, randomized, placebo controlled, double-blind design was used to test the efficacy of imipramine and fluoxetine. METHOD: Patients 4-18 years of age with symptoms of ASD were randomized to 1 of 3 groups: imipramine, fluoxetine, or placebo for 1 week. Daily imipramine dose was 1mg/kg, with the maximum dose being 100mg. Daily fluoxetine dose was 5mg for children weighing >or=40 kg; 10mg for those weighing between 40 and 60 kg; 20mg for those weighing >60 kg. RESULTS: Sixty participants, 16 females and 44 males, had an average body surface area burn of 53% (S.D.=18) and average age of 11 years (S.D.=4). Imipramine subjects received an average daily dose of 1.00+/-0.29 mg/kg. Fluoxetine subjects received an average daily dose of 0.29+/-0.16 mg/kg. Between group differences were not detected. Fifty-five percent responded positively to placebo; 60% responded positively to imipramine; and 72% responded positively to fluoxetine. CONCLUSION: Within the parameters of this study design and sample, placebo was statistically as effective as either drug in treating symptoms of ASD.

Pharmacological treatment of acute stress disorder with propranolol and hypnotics.

INTRODUCTION: Pharmacological treatment of traumarelated mobidity has neither the efficacy nor specificity desired. Thus, several attempts have been made to add new drugs to the usual treatments, in this case with propranolol and hypnotic drugs. METHOD: We offered this treatment to the victims of the March 11, 2004 terrorism attack who were attended within the first week of this attack for psychiatric reasons (n=21) and who also fulfilled criteria for acute stress disorder (ASD) (n=15) and had no contraindications for the treatment (n=3). Trauma intensity was measured with Horowitz impact of events scale (IES). Significant clinical data were collected. RESULTS: Propranolol treatment was associated with clinical remission of target symptoms in 63.6 % of the cases, partial response in 27.3 % and no response in 9.1%. Hypnotic treatment was also associated with clinical remission in 61.5 % and partial response in 38.5 %. Statistically significant correlations were found at the beginning for IES with disability, and after the first month with the propranolol and hypnotic responses. CONCLUSIONS: Propranolol and hypnotic treatments are useful in the decrease of ASD symptoms. IES is very useful to predict disability as well as poor response to propranolol or hypnotic drugs. More studies are needed to confirm the data obtained in our sample.

Risperidone treatment of preschool children with thermal burns and acute stress disorder.

Pharmacologic treatment of acute stress disorder (ASD) is a novel area of investigation across all age groups. Very few clinical drug trials have been reported in children and adolescents diagnosed with ASD. Most of the available, potentially relevant, data are from studies of adults with posttraumatic stress disorder (PTSD). The atypical antipsychotic agents have been reported to be effective as an adjunctive treatment for adults with PTSD. There have been a limited number of studies published regarding atypical antipsychotic treatment of PTSD in children and adolescents, and there is no current literature available on the use of these agents for children with ASD. This report describes the successful treatment of three preschool-aged children with serious thermal burns as a result of physical abuse or neglect. Each of these children was hospitalized in a tertiary-care children's hospital and was diagnosed with ASD. In all cases, risperidone provided rapid and sustained improvement across all symptom clusters of ASD at moderate dosages. Minimal to no adverse effects were reported. These cases present preliminary evidence for the potential use of risperidone in the treatment of ASD in childhood.

Pharmacologic treatment of acute and chronic stress following trauma: 2006.

This article reviews pharmacologic treatment options for posttraumatic stress disorder (PTSD), focusing on goals of pharmacotherapy and the clinical trial evidence for drug treatments available for PTSD. The selective serotonin reuptake inhibitors (SSRIs) are recommended as first-line therapy for PTSD; the roles of these and other drug classes including anticonvulsants, mood enhancers, atypical antipsychotic agents, benzodiazepines, alpha1-adrenergic antagonists, and beta-blockers in achieving improvement in PTSD symptom and outcome scores, achieving remission, and avoiding relapse are discussed. Treatment of PTSD in association with other comorbid conditions is addressed, and the role of pharmacotherapy in treating early PTSD and acute stress disorder is examined. Dosing strategies for the SSRIs sertraline and paroxetine are provided, and an algorithm for PTSD pharmacotherapy is discussed.

Early treatment of acute stress disorder in children with major burn injury.

OBJECTIVE: This study examines retrospectively the response rate of pediatric burn survivors with acute stress disorder to either imipramine or fluoxetine. METHODS: On retrospective chart review, 128 intensive care unit patients (85 boys, 43 girls) with 52%+/- 20% total body surface area burn, length of stay of 32.8+/- 25.2 days, mean age of 9.1+/- 4.7 yrs, and age range of 13 months to 19 yrs met criteria for acute stress disorder after >or=2 days of symptoms and were treated with either imipramine or fluoxetine. If significant improvement did not occur within 7 days, the medication was either increased or switched to the other class. RESULTS: Initially, 104 patients were treated with imipramine and 24 with fluoxetine. A total of 84 patients responded to imipramine: seven of these patients required a higher dose. A total of 18 patients responded to initial fluoxetine treatment. Of 26 nonresponders to the initial medication, 13 imipramine failures and one fluoxetine failure refused further treatment. The other 12 responded to the second medication. Therefore, 114 of 128 treated patients (89%) responded to either fluoxetine (mean dose, 0.30+/- 0.14 mg/kg) or imipramine (mean dose, 1.30+/- 0.55 mg/kg). Response was independent of sex and age but was less for those with burns of >60% total body surface area. The side effects of each medication were not significant. Most patients continued treatment for >or=3 months; some required 6 months of treatment before successful discontinuation. CONCLUSIONS: Early treatment of acute stress disorder with either imipramine or fluoxetine is often able to reduce its symptoms. This is a review of a single hospital's experience in managing psychiatric distress in this very high-risk group of burned children. Additional clinical studies are needed before generalizing these findings.

[Three paradigms in the treatment of posttraumatic stress disorder]. / A poszttraumás-stressz zavar gyógyszeres kezelésének három paradigmája.

There are three different approaches in the pharmacological treatment of posttraumatic stress disorder (PTSD) in the published data. The most frequently implemented approach is to treat patients suffering from the diagnosis of PTSD. Both short-term acute and long-term relapse prevention treatments represent a curative paradigm: with an intention to diminish the symptoms associated with the disorder. Data about efficacy of monoamine oxidase inhibitors and selective serotonin reuptake inhibitors (SSRIs) in the treatment of PTSD are heterogeneous. Data are relatively consistent with regards of efficacy of SSRIs in the treatment of civilian, predominantly female population, regardless of the type of trauma: interpersonal or non-interpersonal trauma. Placebo controlled trial data in the treatment of combat-related PTSD are inconclusive or negative. Three recently published studies provide new approaches to the treatment of male patients, suffering from combat-related PTSD. A relatively young, recently traumatized male, combat-related population showed significant improvement for fluoxetine compared to placebo. An adjuvant 5HT2 antagonist profile may improve the SSRI effect in the treatment of PTSD: nefazodone was significantly superior compared to placebo in the treatment of combat-related PTSD, and risperidone treatment add-on to antidepressants showed significant benefits compared to antidepressant monotherapy in the treatment of combat-related PTSD. The goal of sedative paradigm is to minimize the immediate consequences of the traumatic stress, decrease the fear, anxiety and sleeplessness. Data published about benzodiazepines failed to show effectiveness in the acute management of post-traumatic mental consequences. The intention of the third treatment paradigm is characterized by the secondary prevention of PTSD. Benzodiazepines administered shortly after the traumatic event, failed to prevent the mental consequences of traumatic stress. Two small trials with propranolol administration after the trauma have been shown some benefits compared to placebo or no treatment. PTSD represents a complex disregulation of numerous neurotransmitters and neuromodulators, therefore the complex pharmacological treatment has to consider approaches beyond the current treatment regimens characterized by modulation of monoamine neurotransmission.

General practitioners' knowledge of post-traumatic stress disorder: a controlled study.

BACKGROUND: Post-traumatic stress disorder (PTSD) is common, is associated with substantial morbidity, and is often not recognised in primary care. AIM: To explore whether general practitioners (GPs) have significant gaps in their knowledge of PTSD. DESIGN OF STUDY: A controlled study. SETTING: Primary care in two Scottish regions. METHOD: A validated postal questionnaire consisting of clinical vignettes for PTSD, acute stress reaction, and depression was used to gather the data. The primary outcome measures were the proportion describing 'best practice' management of PTSD and the comparison of this with the control condition, the proportion describing 'best practice' management of depression. The secondary outcome measures were comparisons of PTSD and depression by recognition, drug treatment, and referral. RESULTS: Two-thirds (67.5%) of GPs included PTSD in their differential diagnosis for the PTSD vignette, and 86.8% made a referral to secondary care for the PTSD case. A minority of GPs (42.9%) and only 54.1% of a comparison group of psychiatrists specified the drug treatment of choice for PTSD, a selective serotonin reuptake inhibitor. Only 28.3% of GPs had the knowledge to recognise PTSD and prescribe appropriately, compared with 89.8% for depression (P <0.001). Only 10.2% of GPs described best practice for PTSD, compared with 47.7% for depression (P <0.001). CONCLUSION: Lack of knowledge is among the reasons for less than ideal recognition and management of PTSD in primary care. Further research should aim to explore the implementation of PTSD guidelines in primary care.

Psychological care in trauma patients.

The clinician manages trauma patients in the emergency room, operation theatre, intensive care unit and trauma ward with an endeavour to provide best possible treatment for physical injuries. At the same time, it is equally important to give adequate attention to behavioural and psychological aspects associated with the event. Knowledge of the predisposing factors and their management helps the clinician to prevent or manage these psychological problems. Various causes of psychological disturbances in trauma patients have been highlighted. These include pain, the sudden and unexpected nature of events and the procedures and interventions necessary to resuscitate and stabilise the patient. The ICU and trauma ward environment, sleep and sensory deprivation, impact of injury on CNS, medications and associated pre-morbid conditions are also significant factors. Specific problems that concern the traumatised patients are helplessness, humiliation, threat to body image and mental symptoms. The patients react to these stressors by various defence mechanisms like conservation withdrawal, denial, regression, anger, anxiety and depression. Some of them develop delirium or even more severe problems like acute stress disorder or post-traumatic stress disorder. Physical, pharmacological or psychological interventions can be performed to prevent or minimise these problems in trauma patients. These include adequate pain relief, prevention of sensory and sleep deprivation, providing familiar surroundings, careful explanations and reassurance to the patient, psychotherapy and pharmacological treatment whenever required.