Ila M. P. Linares · Francisco S. Guimaraes; Alan Eckeli; Ana C. S. Crippa Clarissa Trzesniak; Ila M Linares; Érica R Coimbra; Alexandre Veriano Júnior. 1 Research Projects at FAPESP. graduation at Formação de Psicologo from Universidade Federal de São Carlos (), graduation at Bacharelado em. Dec 3, Mateus M. Bergamaschi,1,2,3,* Regina H. C. Queiroz,2,3 Marcos H. N. Chagas,1, 3 Ila M. P. Linares,1,3 Kátia C. Arrais,1,3 Danielle C. G. de.
Linares P. Ila M.
The authors of the studies that used this technique discuss that the poor effectiveness of the interventions performed may be due to the long interval between the occurrence of the traumatic event and the beginning of debriefing Thirteen studies used different types of intervention including, for example, video-based interventions, counseling, and self help programs e.
Six of these studies suggest that the interventions resulted in a decrease in PTSD symptoms when compared to groups that did not receive the intervention. Despite these results, in one of the studies participants received training for stress management before the occurrence of the traumatic event war combat , as well as psychological interventions after the trauma.
Therefore, it is still a matter of debate whether the results obtained stem from the primary or the secondary intervention, that is, if they come from the intervention that preceded or the one that followed the trauma For example, a study by Gidron 29 reported that women participating in a given intervention had a lower frequency of PTSD symptoms than men taking part in the same intervention 29 , which contrasts with previous results from the same group As shown in Table 2 , drugs used in the selected studies included propranolol, escitalopram, docosahexaenoic and eicosapentaenoic acid, hydrocortisone, and morphine.
Among the five trials using pharmacological interventions, only one used a single dose of the test medication On average, test medications were administered for seven days in the remaining studies. Two articles reported results compatible with a lower occurrence of PTSD and related symptoms 12 , These results were based mainly on scales applied after the intervention and at follow-up assessments. In the studies that found no statistically significant effects of pharmacological interventions in the prevention of PTSD, the authors described variables that may have interfered in their results, such as poor adherence to treatment, and suggest that it may be preferable to recruit individuals at increased risk of developing PTSD, such as individuals with high stress levels The article by Bryant et al.
Another study reported that, despite their weak results, propranolol may be useful in the prevention of PTSD because the results of psychophysiological tests suggest that the drug reduces the arousal elicited by exposure to stimuli resembling the traumatic event In addition to the results described above, methodological aspects including sample size, gender and age of participants, type of trauma, assessment scales, randomization procedures, intervention starting time, and follow-up duration also deserve attention, as they can have a direct impact on the results obtained.
In respect to the sample size, we highlight the discrepancy in the number of participants across the studies. Some authors have underscored the need for further investigations involving larger samples in order to confirm the data obtained to date 14 , 22 , Regarding the gender of participants, two of the articles reviewed had discrepancies in the number of female and male participants 20 , Both studies included a higher number of men in the groups of patients undergoing the intervention compared to the other groups.
It should also be noted that, in some studies, samples were formed exclusively by women 13 , 16 , 17 , 23 , 25 , 32 or men Although the authors make no mention to the discrepancies in the numbers of male and female participants, evidence points to a higher vulnerability to PTSD in females Therefore, studies with unbalanced gender distributions may not be as representative as studies with gender-balanced samples in what concerns the prevalence of the disorder.
This can be, however, a limitation that is difficult to overcome in populations that are more vulnerable to certain types of trauma and with a high predominance of one gender, as in the case of soldiers mainly men or victims of sexual abuse mainly women. Only one of the articles reviewed did not inform the mean age of participants 8.
This is highly relevant because, although the onset of PTSD may occur at any age, it is more common in young adults since they are more prone to have the type of experiences that trigger the disorder Still in respect to the age of study participants, there was less homogeneity in the data presented by some authors 7 , 17 , 34 - These articles do not discuss the age discrepancies in their samples, as well as the possible influence of this factor on their results.
From the 29 articles reviewed, four had no uniform samples in terms of the type of trauma experienced, that is, these studies assessed more than one type of trauma 17 , 18 , 22 , There is evidence in the literature of correlations between the type of trauma experienced and gender-related vulnerability In this sense, variations in the types of trauma assessed in a same study can be seen as a limitation that hinders the reproducibility of its results.
Despite that, there was no standard in what concerns the instruments used in the articles reviewed. In general, the studies included scales to assess symptoms of depression and anxiety.
The lack of homogeneity in the types of instruments used in the studies also hampers the comparison of results available to date, as well as the generalization of findings. The randomization and blinding strategies used in the trials were also examined in this review. Only one of the articles included informed that the study sample had not been randomized In respect to the study design, only two articles did not describe the inclusion of comparison groups 25 , The remaining articles included one or more comparison groups.
Still regarding the study design, the trial by Bryant et al. The time between the occurrence of the trauma and the beginning of the intervention varied greatly across studies, from 6 hours 31 to 10 weeks 9.
It has been argued that the shorter the interval between the traumatic event and the beginning of the intervention, the more likely is the blockade of the consolidation of aversive memories 17 with a consequent reduction in the possible negative emotional consequences of the trauma. Regarding follow-up assessments, all the studies reviewed included this type of analysis; however, the frequency and the interval between assessments varied.
Some limitations related to follow-up assessments were pointed in the studies reviewed, such as excessively short intervals between assessments 17 and poor treatment adherence by participants during long follow-up periods Finally, one limitation described in some studies refers to the intrinsic difficulties of proving the efficacy of early interventions, since a significant part of volunteers may not be vulnerable to the development of PTSD.
Future research should seek to determine reliable criteria for the identification of trauma victims at risk of developing PTSD, which would allow improved assessments of the interventions performed.
As an example, psychological and biological factors are known to influence the vulnerability to PTSD, including internalizing behavioral problems, psychiatric comorbidities, alterations in the hypothalamic-pituitary adrenal axis, brain abnormalities, and genetic factors 39 , The main difficulty in the analysis of the 29 articles included in this review rose from the significant methodological variations across the studies, as discussed above.
In general terms, we conclude that studies using psychological interventions lack homogeneity in respect to the type of intervention and measures used to assess intervention outcomes. Pharmacological trials were less frequent in the area of PTSD prevention and should have their findings replicated, in addition to expanding the range of drugs tested.
Possible investigation targets for future research include cannabinoid compounds, and especially cannabidiol CBD , since this compound seems to play an important role in the blockade of the reconsolidation of aversive memories In addition, preclinical studies provide support for the test of oxytocin as a promising strategy in the prevention of PTSD-like manifestations Despite the methodological issues described above, the studies reviewed further our understanding about PTSD and interventions aimed at preventing the disorder or minimizing post-trauma symptoms 43 - Importantly, many of the articles reviewed suggest that pharmacological and psychological interventions are effective in this regard.
However, we were unable to find studies that combined pharmacological and psychological interventions. Since this association has proved useful in the management of other psychiatric conditions e. Early interventions for PTSD: Prevention of Mental Disorders. Meta-analytic procedures for social research rev. Posttraumatic stress following acute medical trauma in children: Clin Child Fam Psychol Rev. Emotional or educational debriefing after psychological trauma: Escitalopram in the prevention of posttraumatic stress disorder: Early cognitive-behavioural therapy for post-traumatic stress symptoms after physical injury: Treating acute stress disorder: Preventing psychological trauma in soldiers: Br J Med Psychol.
The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: Effectiveness of a counseling intervention after a traumatic childbirth: Translating research findings to PTSD prevention: Randomized controlled evaluation of an early intervention to prevent post-rape psychopathology. Pilot study of an exposure-based intervention in the ED designed to prevent posttraumatic stress disorder.
Am J Emerg Med. Early intervention may prevent the development of posttraumatic stress disorder: A randomised controlled trial to assess the effectiveness of providing self-help information to people with symptoms of acute stress disorder following a traumatic injury.
Pharmacotherapy to prevent PTSD: Results from a randomized controlled proof-of-concept trial in physically injured patients. Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Changes in negative beliefs following three brief programs for facilitating recovery after assault.
Internet-based early intervention to prevent posttraumatic stress disorder in injury patients: J Med Internet Res. Debriefing with brief group psychotherapy in a homogenous group of non-injured victims of a terrorist attack: Brief Treat Crisis Interv. Emergency department predictors of posttraumatic stress reduction for trauma-exposed individuals with and without an early intervention. J Consult Clin Psychol.
Interactive effects of memory structuring and gender in preventing posttraumatic stress symptoms. J Nerv Ment Dis. A study of the protective function of acute morphine administration on subsequent posttraumatic stress disorder. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Group counseling for mothers after emergency cesarean section: Javidi H, Yadollahie M.
Participants were monitored for up to 6 months and reported no depressive symptoms. Changes in Visual Analogue Mood Scale factors induced by simulation of the public speaking test. B, baseline; P, prestress; A, anticipatory speech; S, speech performance; F1, poststress 1; and F2, poststress 2.
Points indicate mean and vertical bars indicate standard error of the mean. Systolic and diastolic pressure did not show significant repeated-measures ANOVA effect in phases and phase by group interaction.
HR showed a significant effect of phase F 3. Changes in heart rate, systolic, and diastolic pressure induced by simulation of public speaking test. The anxiogenic effects occurred selectively during anticipatory and performance speech, without interfering with the prestress phase, meaning that the drug effects occurred selectively in response to an aversive situation.
Endocannabinoids implication with social anxiety is in accordance with dense expression of CB1 receptors in brain regions related to anxiety, fear, and aversion, including the medial prefrontal cortex, hippocampus, amygdala, and periaqueductal gray Howlett et al. Preclinical studies showed that anxiogenic-like effects of CB1 antagonists tend to be more evident when animals are subjected to high levels of aversion Haller et al. Anandamide-hydrolysis inhibitors are more efficacious as anxiolytic drugs, when tested in a highly aversive environment Naidu et al.
The basal levels of endocannabinoid synthesis and release tend to be low; however, the activity of this system is enhanced in response to neural activation when experimental animals are exposed to threatening stimuli, when endocannabinoids would work to counteract fear responses Moreira and Wotjak, ; Riebe et al. This would explain why CB1 antagonists tend to modify behavioral responses preferentially under high levels of aversion, without significant baseline effects. An experimental study with healthy volunteers revealed that rimonabant reduced incidental recall of positive self-relevant adjectives Horder et al.
The role for the endocannabinoid system in anxiety emerged primarily from clinical trials of rimonabant's effect on obesity and related metabolic disorders treatment RIO Studies. These investigations revealed that anxiety and depression are important side effects of this drug, as compared with placebo Christensen et al. The present work indirectly suggests that facilitating CB1 receptor signaling may alleviate the consequences of aversive stimuli with important implication in the treatment of psychiatric disorders.
Rimonabant increased self-reported anxiety induced by public speaking in healthy subjects, without interfering with prestress levels, supporting the notion that the endocannabinoid system may work on-demand to counteract the consequences of aversive stimuli. Additional double-blind, placebo controlled trials are desirable to determine the precise endocannabinoids mechanism in anxiety and anxiety disorders. The authors acknowledge Sandra Bernardo and Selma Pontes for their clinical support.
National Center for Biotechnology Information , U. Author manuscript; available in PMC Aug Queiroz , 2, 3 Marcos H. Chagas , 1, 3 Ila M. Arrais , 1, 3 Danielle C. Queiroz , 4 Antonio E. Nardi , 3, 5 Marilyn A. Huestis , 6 Jaime E. Hallak , 1, 3 Antonio W. Author information Copyright and License information Disclaimer.
The publisher's final edited version of this article is available at Hum Psychopharmacol. See other articles in PMC that cite the published article. Methods Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design.
Results Twelve participants received oral placebo and 12 received 90 mg rimonabant. Conclusions Cannabinoid-1 antagonism magnifies the responses to an anxiogenic stimulus without interfering with the prestress phase. Screening procedure and clinical assessment Participants, recruited by telephone and printed advertisements, were screened through self-assessment diagnostic instruments.
Psychological and physiological measurements The state-anxiety level and other subjective states were evaluated during the test through the Visual Analogue Mood Scale VAMS Portuguese version Norris, ; Zuardi and Karniol, , grouped into four factors: Procedure The simulation of the public speaking test was the same as used by McNair et al.
Statistical analysis Clinical and demographic characteristics were investigated via boxplot and Shapiro—Wilk normality tests; therefore, they were analyzed by nonparametric tests gender, socioeconomic level, BAI, and social phobia inventory and by analysis of variance ANOVA for one factor, age and body mass index. Table 1 Clinical and demographic characteristics of participant groups.
Open in a separate window. Physiological measures Systolic and diastolic pressure did not show significant repeated-measures ANOVA effect in phases and phase by group interaction. An inventory for measuring clinical anxiety: J Consult Clin Psychol. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients.
Efficacy and safety of the weight-loss drug rimonabant: Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight.
The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers. Effect of chlorimipramine and maprotiline on experimental anxiety in humans.
Adverse health effects of non-medical cannabis use. Adverse effects of cannabis. Revista Brasileira De Psiquiatria. Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice. Interactions between environmental aversiveness and the anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rats.
Psychopharmacology Berl ; The FAST alcohol screening test. Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers. International Union of Pharmacology. Classification of cannabinoid receptors.
Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Cannabinoid CB1 receptor deficiency increases contextual fear memory under highly aversive conditions and long-term potentiation in vivo.
Modulation of anxiety through blockade of anandamide hydrolysis. Acta Physiol Oxf ;
Early interventions for the prevention of PTSD in adults: a systematic literature review
Ila M.P. LinaresI; Clarissa TrzesniakI; Marcos Hortes N. ChagasI; Jaime E. C. HallakI; Antonio E. NardiII; José Alexandre S. CrippaI. IDepartment of. Review article. Early interventions for the prevention of PTSD in adults: a systematic literature review. ILA M. P. LINARES. FELIPE D'ALESSANDRO F. CORCHS. D.J. Veltman, W.E. Tuinebreijer, D. Winkelman, A.A. Lammertsma, M.P. Witter, R.J. Dolan, P.M. EmmelkampNeurophysiological correlates of habituation during .