Gelpin E, Bonne O, Peri T, Brandes D, Shalev AY. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry 57: 390-394

The Center for Traumatic Stress, Department of Psychiatry, Hadassah University Hospital, Jerusalem, Israel.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 10/1996; 57(9):390-4.
Source: PubMed


Most types of psychotropic drugs have been tried in the treatment of chronic posttraumatic stress disorder (PTSD), but have yielded limited results. Theory and retrospective research predict that early treatment may be more efficacious. Specifically, high-potency benzodiazepines have been recommended for the treatment of acute responses to trauma and for prevention of PTSD. This study prospectively evaluates the effect of early administration of benzodiazepines on the course of PTSD and PTSD symptoms.
Thirteen trauma survivors (the benzodiazepine group) were treated within 6.7 +/- 5.8 days after the trauma (range, 2-18) with either clonazepam (N = 10, 2.7 +/- 0.8 mg/day) or alprazolam (N = 3, 2.5 mg/day). Thirteen other trauma survivors, pair-matched with subjects in the active treatment group for gender and symptom severity in the first week after the trauma, constitute the control group. Both groups were reevaluated 1 and 6 months after the trauma for PTSD symptoms (Horowitz Impact of Event Scale; Mississippi Rating Scale for Combat-Related PTSD-civilian trauma version), PTSD status (Clinician Administered PTSD Scale), state anxiety, depression, and resting heart rate.
Subjects in the benzodiazepine group did not differ from controls in 1-month and 6-month PTSD and anxiety scores. Repeated measures ANOVA showed no group or group-by-time effect on psychometric measures. A trend toward group-by-time interaction in resting heart rate was noted (progressive decrease in the benzodiazepine group). Nine benzodiazepine subjects and 3 controls met PTSD diagnostic criteria 6 months after the trauma.
Contrary to expectations, the early administration of benzodiazepines to trauma survivors with high levels of initial distress did not have a salient beneficial effect on the course of their illness, while reducing physiologic expression of arousal.

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    • "Benzodiazepines are also known for enhancing emotional memory, which acutely after trauma may impact traumatic memory consolidation and worsen PTSD symptoms (for a review, see [46]). Acute benzodiazepine administration was positively associated with PTSD in two small trials of injury victims [47] [48]. These findings, along with preclinical evidence that acute poststressor alprazolam administration negatively affects behavioral outcomes to subsequent stress exposure [49], suggest a negative effect of benzodiazepines on natural recovery following trauma. "
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    ABSTRACT: Pharmacological intervention during traumatic memory consolidation has been suggested to prevent posttraumatic stress disorder (PTSD). The aim of this study was to examine the association between prescription of early pharmacotherapy and the risk of developing PTSD symptoms following traumatic injury. The use of opiate analgesics, beta-adrenergic blockers, corticosteroids and benzodiazepines within 48 h postinjury was documented based on hospital charts for 629 Level 1 trauma center patients. PTSD symptoms were assessed using structured clinical interviews. Primary outcome was 6-week PTSD symptoms. Secondary outcomes were PTSD diagnoses at 6 weeks and during 1 year posttrauma. Linear regression analyses showed that opiate administration within 48 h was negatively associated with PTSD symptoms at 6 weeks (β=-0.14, P=.009) after controlling for demographic and injury-related characteristics and concurrent pharmacotherapy. Fewer patients with opiates had a PTSD diagnosis at 6 weeks (P=.047) and during 1 year posttrauma (P=.013) than patients with none of the specified pharmacotherapies. Low prescription frequency of beta-blockers (3.8%), corticosteroids (2.2%) and benzodiazepines (7.8%) precluded further examination of their role in the development of PTSD symptoms because of limited statistical power. This study suggests a possible beneficial influence of opiate administration within 48 h posttrauma on the development of PTSD symptoms. Future studies may evaluate the effectiveness of inhospital opiate analgesics compared to placebo in preventing PTSD and may focus on the mechanisms underlying the effect of opiates in preventing PTSD. Copyright © 2015. Published by Elsevier Inc.
    General Hospital Psychiatry 03/2015; 37(3). DOI:10.1016/j.genhosppsych.2015.02.010 · 2.61 Impact Factor
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    • "The database having been established so far, however, is still insufficient to correctly assess the proper preventive potential of any of these drugs regarding the incidence of later PTSD.50-54 On an empirically informed level of assessment one has to keep in mind that several psychological preventive strategies are also far from being conclusive in their efficacy to reduce the risk of PTSD after trauma exposure and their acceptance by affected patients in an emergency setting.55,36 Although all pharmacological tools that have been investigated in the indication of potentially preventive effects have been well tolerated without any serious side effects, a particular caveat has been brought up in public opinion: drugs altering memory might also alter the core feeling of personal identity. "
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    ABSTRACT: Post-traumatic stress disorder (PTSD) may be associated with long-lasting psychological suffering, distressing psychosocial disability, markedly reduced health-related quality of life, and increased morbidity and mortality in a subgroup of individuals in the aftermath of serious traumatic events. Both etiopathogenesis and treatment modalities of PTSD are best conceptualized within a biopsychosotial model. Pharmacotherapy may lay claim to a major role in the multimodal treatment approaches. Here we outline two different pharmacotherapeutic trends that aim to modify the encoding, consolidation, and rehearsal of traumatic memory in order to reduce the risk of PTSD immediately after trauma exposure on the one hand, and that endeavor to treat the clinical state of PTSD on the other. The theoretical rationales of both pharmacological strategies are the complex neurobiological underpinnings that characterize traumatic memory organization and clinical PTSD. Meanwhile, promising data from randomized controlled trials have been obtained for both approaches. Empirical evidence may inform clinicians in their clinical efforts for this special group of patients. The efficacy of several classes of drugs that have been investigated within a context of research should be evaluated critically and still have to stand the test of effectiveness in daily clinical practice. From a patient perspective, empirical results may serve as a psychoeducative guideline to what pharmacotherapeutic approaches may realistically achieve, what their risks and benefits are, and what their limits are in contributing to reducing the often major chronic suffering caused by serious traumatic events. Ethical issues have to be considered, particularly in the context of pharmacological strategies projected to prevent PTSD in the aftermath of traumatic exposure.
    Dialogues in clinical neuroscience 06/2014; 16(2):227-37.
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    • "There are commonly used in clinical practice as adjunctive medications in PTSD, targeting symptomatic treatment of sleep disturbance, irritability and hyper arousal symptoms. Experimental studies had shown that facilitation of gabaergic function by the benzodiazepine midazolam disrupted reconsolidation processes of fear memory [10] However, only a limited number of randomized clinical trials have been conducted to evaluate the effects of benzodiazepines in PTSD [58] [59] [60] and evidence for their effectiveness as a treatment for PTSD is lacking, as reported by Ipster and Stein in their recent systematic meta-analysis comparing the efficacy of different medications in treating PTSD. [6] 3.2.5. "
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    ABSTRACT: Introduction: Post-traumatic stress disorder (PTSD) is a frequent and disabling condition that occurs after exposure to a traumatic event, and Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first-line treatment approach for this disorder. However, a large proportion of patients remain symptomatic and other pharmacological agents have been investigated, based on the understanding of the underlying biological dysfunctions of PTSD. Methods: We conducted a review of the literature on the pharmacological options for PTSD other than the antidepressants, using MedLine and Web of Science databases, with search terms including the pharmacologic class of each agent plus PTSD, or pharmacotherapy, or fear conditioning. The literature review covered articles published until august 2012, including reviews and original articles. Results: Agents like antipsychotics, anticonvulsants, benzodiazepines, anti-adrenergic agents, have been studied in randomized clinical trials (RCTs), with general positive results for antipsychotics, especially as adjunct therapy, and for prazosin for sleep-related disturbances. However, one important target for novel medications is the modulation of the fear conditioning process, through the alteration of retrieval/reconsolidation or enhancement of fear extinction. This is traditionally targeted in prolonged exposure therapy, but pre-clinical findings from studies investigating agents like propanolol, clonidine, N-Methyl-D-aspartic Acid Receptor (NMDAR) compounds, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and cannabinoids, indicate promising results in affecting the fear conditioning process and thus improving PTSD core symptoms. Discussion: Antipsychotics can be considered a reasonable alternative option to PTSD, with the largest body of evidence for risperidone, even though larger RCTs are warranted. Prazosin is also a promising agent, especially for sleep-related disturbances, while anticonvulsants and benzodiazepines lack empirical support. However, the most promising area for pharmacotherapy in PTSD is the modulation of the fear conditioning process, through agents used in adjunct to exposure therapy.
    02/2013; 10(2). DOI:10.2174/157488471002150723122127
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