Ila M. P. Linares1, Felipe D’Alessandro F. Corchs2, Marcos Hortes N. Chagas3, Antonio Waldo Zuardi1, Rocio Martın-Santos4, José Alexandre S. Crippa1
¹ Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), and National Institute for Translational Medicine (INCT, CNPq), Ribeirão Preto, SP, Brazil.
2 Núcleo Paradigma de Análise do Comportamento, Department of Psychiatry, University of São Paulo Medical School (FMUSP), São Paulo, SP, Brazil.
3 Centro de Ciências Biológicas e da Saúde, Departamento de Gerontologia, Universidade Federal de São Carlos (UFSCar), São Carlos, SP, Brazil.
4 Department of Psychiatry, Institute of Neurosciences, Hospital Clınic, IDIBAPS, CIBERSAM, Barcelona, Spain.
Received: 8/24/2016 – Accepted: 11/28/2016
Address for correspondence: Ila M. P. Linares. Hospital das Clínicas, 3º andar. Av. Bandeirantes, 3900 – 14048-900 – Ribeirão Preto, SP, Brazil. Telephone: +55 (16) 3602-2703/Fax: +55 (16) 3602-2544. E-mail: [email protected]
Background: Secondary interventions are implemented within a short interval following the occurrence of traumatic events with the purpose of preventing the onset of PTSD. Objective: Analyze the results of studies that assessed post-trauma interventions in adults aimed at preventing the onset of PTSD or symptoms related to PTSD. Methods: We performed literature searches using the search expression [(Early intervention OR secondary prevention) AND (Post traumatic stress disorder OR PTSD)] for articles published until October 2016. Among the references found, 29 fulfilled the selection criteria established for the review. Data were divided and analyzed according to the type of intervention: pharmacological or psychological. Results: Psychological measures used in the studies lack homogeneity regarding the type of intervention and the assessment of intervention outcomes. Pharmacological interventions were less frequent and findings require replication, together with an expansion in the types of substances investigated. In general, many of the studies reviewed suggest that both pharmacological and psychological interventions are effective in the prevention of PTSD. Discussion: Future trials should be focused on determining the best interventions for the secondary prevention of PTSD. The combination of psychological and pharmacological interventions for post-trauma patients poses opportunities and challenges that remain unexplored.
Linares IMP et al. / Arch Clin Psychiatry. 2017;44(1):23-9
Keywords: Early intervention, post-traumatic stress disorder, literature review.
According to the DSM-IV, post-traumatic stress disorder (PTSD) is characterized by a set of responses triggered by exposure to a significant traumatic event. The condition generally involves four groups of symptoms consisting of persistent re-experiencing of the traumatic event in one or more forms (e.g., in nightmares or through feelings similar to those experienced in the traumatic event), constant avoidance of stimuli associated with the trauma, recurrent arousal responses, and cognition or mood alterations associated with the traumatic event. These symptoms should last more than a month and be followed by significant impairment or distress for the individual1.
Interventions implemented shortly after the occurrence of the trauma are aimed at the secondary prevention of PTSD, that is, they are attempts to avoid the development of the disorder in individuals who have already been exposed to the traumatic event and reduce occasional harms resulting from the experience. Secondary interventions have received increasing attention because of the high prevalence of PTSD in the population (6.8% in the American population according to Kessler2 and the protective action of post-trauma interventions3. In addition, the World Health Organization has listed important impacts of PTSD: economical and on social, interpersonal, and occupational functioning, adding that prevention strategies should be broadly promoted4.
In this article, we present the results of a systematic literature review on post-trauma interventions for adults aimed at preventing the onset of PTSD or symptoms related to the disorder. We were unable to use a quantitative approach such as a meta-analysis because (a) the information required for the calculation of effect sizes was not always available, which could restrict the analysis to a small subset of studies; (b) there were important differences regarding secondary variables in the studies (e.g., gender, type of trauma, medication, comorbid conditions); (c) different methods were used to analyze data obtained through different forms of investigation; and (d) meta-analysis have intrinsic limitations related to the estimates of unpublished negative results (the “file drawer problem”5). The review was also limited to studies involving adult participants, since current models show that the development of PTSD in children is different from that of adults in terms of biological, psychological, and social aspects and the interactions between them6.
We made a search using the search expression [(Early intervention OR secondary prevention) AND (Post traumatic stress disorder OR PTSD)] on the electronic databases MEDLINE, Web of Knowledge, SciELO, PsycINFO, and LILACS. Articles published until October 2016 were included, with no previous time limit. The reference lists of the selected articles were manually checked for additional references relevant to the topic of the review.
The articles included in the review were published in English, Spanish or Portuguese. We included studies involving humans aged 18 or above who had suffered any type of trauma and which presented results of interventions effected up to one month after the traumatic event (this criterion was based on DSM-5, where PTSD is characterized by disturbances lasting more than one month after the trauma). In respect to the type of intervention, we included articles that assessed the effects of pharmacological or psychological trials.
Review articles, letters to the editor, editorials, abstracts published in the annals of scientific events, case reports, and articles dealing with other disorders different from PTSD or its prevention were not included in this review.
The electronic searches returned 22 articles that fulfilled the inclusion criteria for the review. Seven additional articles were included after hand-search of the reference lists of those articles. Figure 1 illustrates the process of article search, selection, and exclusion.
Results and discussion
Table 1 presents the clinical and demographic data of the participants included in the 29 articles reviewed, whereas Table 2 describes the methodological aspects of the studies. Results were divided according to the type of intervention (pharmacological or psychological). From the 29 articles reviewed, 16 reported significant effects of interventions for the prevention of PTSD or symptoms related to the disorder7-22. Of these, 22 studies used psychological interventions and 7 used pharmacological interventions (Table 2).
We considered as psychological interventions those approaches that were not based on the administration of pharmacological substances. The main psychological approaches used in the studies were cognitive behavioral therapy (CBT) and debriefing, followed by other approaches described below.
Cognitive behavioral therapy (CBT)
Four of the six studies that used CBT or related techniques reported results compatible with reduced occurrence of PTSD or PTSD-related symptoms in groups who underwent interventions in relation to control groups9,17-19. In the study by Mouthaan et al.24, which did not report reductions in the occurrence of PTSD, the authors discuss the fact that one-fifth of the volunteers failed to adhere to the intervention program. Another possible explanation for these results could be related to the low level of PTSD symptoms in the sample, which may have hampered the detection of improvements in the group that received the intervention.
In respect to the methodological aspects of these studies, the duration of treatment varied between 1-12 weeks and follow-up assessments were made in all the investigations. Regarding the type of intervention, there was no homogeneity in respect to the techniques described in the articles. Despite the positive results, additional studies involving larger and more homogeneous samples and longer follow-up periods are desirable to clarify the effects of such interventions.
Four articles described the use of interventions based on a techniques know as debriefing7,11,25,26. Debriefing involves different forms of brief counseling and is aimed at allowing victims of psychological trauma to process their experiences cognitively and emotionally. The technique is generally applied hours after the occurrence of a traumatic event28. The results obtained with this technique are convergent in respect to the poor efficacy of the method in the prevention of PTSD and, in some cases, there were reports of symptom worsening. 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 debriefing26.
Other types of psychological intervention
Thirteen studies used different types of intervention including, for example, video-based interventions, counseling, and self help programs (e.g., psychoeducational and motivational techniques). 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 trauma11.
In respect to the studies that found no significant changes in PTSD and PTSD-related symptoms, some contradictions should be mentioned. For example, a study by Gidron29 reported that women participating in a given intervention had a lower frequency of PTSD symptoms than men taking part in the same intervention29, which contrasts with previous results from the same group14.
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 medication30. 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 symptoms12,22. 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 levels21.
The article by Bryant et al.30 reported that, although no significant results were found in terms of PTSD symptoms, the acute administration of morphine had a protective effect related to the severity of PTSD. 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 event31.
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.
Other relevant aspects
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 date14,22,25.
Regarding the gender of participants, two of the articles reviewed had discrepancies in the number of female and male participants20,39. 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 women13,16,17,23,25,32 or men11. 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 females33. 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 participants8. 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 disorder33. Still in respect to the age of study participants, there was less homogeneity in the data presented by some authors7,17,34-36. 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 trauma17,18,22,28. There is evidence in the literature of correlations between the type of trauma experienced and gender-related vulnerability37. 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.
The most frequently used scale in the studies included in this review was the Clinician Administered PTSD Scale (CAPS38), designed to assess PTSD symptoms. 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 randomized22. Four of the studies were described by their authors as single-blind13,14,18,22, five did not include information about whether they were double-blind trials or not7,18 27,32,34, and one informed that the trial was “not double-blind”. In respect to the study design, only two articles did not describe the inclusion of comparison groups25,30. The remaining articles included one or more comparison groups. Still regarding the study design, the trial by Bryant et al.30 used an observational design, assessing the use of morphine after the trauma and the development of PTSD-related symptoms in the follow-up.
The time between the occurrence of the trauma and the beginning of the intervention varied greatly across studies, from 6 hours31 to 10 weeks9. 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 memories17 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 assessments17 and poor treatment adherence by participants during long follow-up periods24. 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 factors39,40.
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 memories41. In addition, preclinical studies provide support for the test of oxytocin as a promising strategy in the prevention of PTSD-like manifestations42.
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 symptoms43-48. 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.g., OCD, panic disorder, depression, alcohol dependence), the use of combined interventions in post-trauma volunteers could bring important contributions to the field.
Conflict of interest
The authors have no conflict of interest related to the topic of this article. The funding agency had no role in the study design or in the decision to submit the paper for publication.
JAC and AWZ are recipients of fellowship awards from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). The present study is supported by a CNPq Grant (CNPq/MS/SCTIE/DECIT N° 26/2014 – Pesquisas sobre Distúrbios Neuropsiquiátricos; 466805/2014-4). RM-S was also supported by the Generalitat de Cataluny/Support a les activitats del Grups de Recerca): SGR2014/1411.