Trauma-focused treatments for depression. A systematic review and meta-analysis

Sarah K Dominguez; Suzy J M A Matthijssen; Christopher William Lee

doi:10.1371/journal.pone.0254778

. 2021 Jul 22;16(7):e0254778. doi: 10.1371/journal.pone.0254778

Trauma-focused treatments for depression. A systematic review and meta-analysis

Sarah K Dominguez ¹, Suzy J M A Matthijssen ^2,³, Christopher William Lee ^1,^4,^*

Editor: Andrea Martinuzzi⁵

PMCID: PMC8297785 PMID: 34292978

Abstract

Background

Trauma-focused treatments (TFTs) have demonstrated efficacy at decreasing depressive symptoms in individuals with PTSD. This systematic review and meta-analysis evaluated the effectiveness of TFTs for individuals with depression as their primary concern.

Methods

A systematic search was conducted for RCTs published before October 2019 in Cochrane CENTRAL, Pubmed, EMBASE, PsycInfo, and additional sources. Trials examining the impact of TFTs on participants with depression were included. Trials focusing on individuals with PTSD or another mental health condition were excluded. The primary outcome was the effect size for depression diagnosis or depressive symptoms. Heterogeneity, study quality, and publication bias were also explored.

Results

Eleven RCTs were included (n = 567) with ten of these using EMDR as the TFT and one using imagery rescripting. Analysis suggested these TFTs were effective in reducing depressive symptoms post-treatment with a large effect size [d = 1.17 (95% CI: 0.58~ 1.75)]. Removal of an outlier saw the effect size remain large [d = 0.83 (95% CI: 0.48~ 1.17)], while the heterogeneity decreased (I² = 66%). Analysis of the 10 studies that used EMDR also showed a large effect [d = 1.30 (95% CI: 0.67~1.91)]. EMDR was superior to non trauma-focused CBT [d = 0.66 (95% CI: 0.31~1.02)] and analysis of EMDR and imagery rescripting studies suggest superiority over inactive control conditions [d = 1.19 (95% CI: 0.53~ 1.86)]. Analysis of follow-up data also supported the use of EMDR with this population [d = 0.71 (95% CI: 1.04~0.38)]. No publication bias was identified.

Conclusions

Current evidence suggests that EMDR can be an effective treatment for depression. There were insufficient RCTs on other trauma-focused interventions to conclude whether TFTs in general were effective for treating depression. Larger studies with robust methodology using EMDR and other trauma-focused interventions are needed to build on these findings.

Introduction

It is estimated that more than 264 million individuals worldwide suffer from depression, with the World Health Organisation stating that it is currently the leading cause of disease burden worldwide [1, 2]. Despite the pervasive nature of this disorder, and a substantial body of evidence devoted to understanding and shaping best-practice psychological interventions, approximately 40% of the individuals suffering from depression fail to respond positively to these evidence-based treatments [3]. In a meta-analysis on the effects of psychotherapies for major depressive disorder (MDD), 62% of the patients were found to no longer meet the criteria for MDD [4]. However, 43% of the participants in control conditions and 48% of people in care-as-usual conditions also no longer met the criteria for the diagnoses. This suggests the additional value of psychotherapy to be 14% [4]. Further, of the individuals who do recover, more than half are likely to relapse within several years of receiving these interventions [5]. Although these relapse rates may reflect the episodic nature of the disorder [6], further investigation into evidence-based interventions is warranted.

The causes of depression and the factors that maintain this disorder are likely to be numerous. One predisposing factor for depression repeatedly identified in the literature is the experience of aversive life events in childhood [7, 8]. Individuals who identify such events are likely to have more severe depressive symptoms and a poorer response to evidence-based treatments compared with those who do not identify a history of adversities [9]. These adversities may also be involved in perpetuating depressive symptoms. The nature of these adversities that impact later functioning is varied and subjective [10]. For a diagnosis of PTSD the adverse experience needs to involve actual or threatened injury or death or sexual assault [11, 12]. However, this restricted criterion does not allow for all adversities that cause ongoing distress or impairment [10, 13]. For example, there is evidence that other, objectively less severe events, such as bullying or neglect, also have lasting psychological impact [10, 14].

While the link between depression and adversities is well established [8, 9], how to mitigate the impact of this link in individuals with depression, in the absence of PTSD is less clear. One way to investigate this is to look at the symptoms related to these adversities that may be maintaining the depression. One such symptom is the existence of intrusive memories [15–17]. In a recent meta-analysis, adults with depression were found to experience intrusive memories more frequently than healthy controls and at a similar frequency to adults with PTSD [16]. Further, in another meta-analysis, the frequency and aversiveness of such memories were found to be associated with severity of a patient’s depression [18]. There is evidence that individuals with intrusive memories often engage with problematic strategies such as avoidance or rumination on the event or related thoughts and emotions, which further maintains depressive symptoms [18–20]. Avoidance can be cognitive, behavioural or experiential, while rumination is defined as repeated, uncontrollable, self-focused negative thinking related to the past [16, 18, 21]. Both avoidance and rumination of intrusive memories are strongly correlated with depression diagnosis and severity, and poorer prognosis [17, 18, 21, 22]. Therefore, it seems plausible to target these intrusive memories and related behaviours, to enhance depression treatment [16, 18].

Trauma-focused treatments (TFTs) are a range of treatments that are primarily used to address symptoms of PTSD, including intrusive memories, related cognitions, emotions and experiential avoidance [23]. TFTs include prolonged exposure, trauma-focused cognitive behavioural therapy (CBT), eye movement desensitisation and reprocessing (EMDR), cognitive processing therapy, exposure-based cognitive therapy, and imagery rescripting (ImRs). The impact of TFTs on depressive symptoms for individuals with PTSD has been well documented [24–27]. However, until recent years the impact of trauma therapies on depressive symptoms, in the absence of a PTSD diagnosis, has not been investigated.

An increasing number of clinical trials have been conducted investigating a range of TFTs as a treatment for depression outside a PTSD diagnosis, including exposure-based cognitive therapy [28], EMDR [29], trauma-focused-CBT [30], and ImRs [31]. Due to the number of published manuscripts relating to using a TFT for depression, narrative reviews of both EMDR [32, 33] and ImRs [34] have been published. These reviews highlight that each TFT has been found to be effective with depressed individuals in the absence of a comorbid PTSD diagnosis. However, at the time of designing the current study, there was no meta-analysis on the effectiveness of treating depression with a TFT when PTSD was not the presenting issue.

The aim of this paper was to provide a synthesised analysis of the effects of TFTs on depression to date. It was hypothesised that, for individuals with depression as their primary complaint, those who receive a TFTs would be more likely to show a decrease in depressive symptoms and increase in the likelihood of remission than those who receive a control condition. This hypothesis was assessed via a systematic review of all relevant randomised controlled trials (RCTs) and a meta-analysis of the pooled data.

Method

Search strategy

A comprehensive search was conducted in October 2019 in Cochrane CENTRAL; Pubmed, EMBASE and Proquest: PsycInfo, to attempt to identify all published and unpublished RCTs. No language restrictions were set so long as data and an English abstract were available. Articles of interest were identified using the following search terms: "eye movement desenti?ation and reprocessing" OR "eye movement desenti?ation” OR “’EMDR” OR “trauma focused treatment” OR “trauma focused CBT” OR “TF-CBT” OR “brief eclectic psychotherapy” OR”BEPP” OR “exposure” OR “cognitive processing therapy” OR”CPT” OR “narrative exposure therapy” OR “NET” OR “imagery rescripting AND depressi*, dysthymic OR MDD OR MDE.

In addition to this search, the reference lists of relevant reviews and studies were screened. Finally, the WHO international clinical trials registry platform was screened to identify any unpublished papers that were missed. Prior to the search commencing the review was registered with PROSPERO (ID 155541).

Selection criteria

Papers included in the analysis were based on the following PICO:

Population

Individuals with a primary mental health diagnosis or subclinical symptoms of major depressive disorder, persistent depressive disorder, dysthymia, premenstrual dysphoric disorder, depressive disorder due to another medical condition, other specified depressive disorder or unspecified depressive disorder. Studies that required participants to have a PTSD diagnosis were excluded from our analysis.

Intervention

Any treatment that was originally designed to target symptoms of posttraumatic stress disorder. This includes—but may not be limited to—EMDR; trauma-focused CBT, brief eclectic psychotherapy, (prolonged/imaginary) exposure, cognitive processing therapy, narrative exposure therapy, and ImRs.

Comparator

All other psychological and pharmacological treatments including standard care and waitlist.

Outcomes

Symptoms of depression measured with any valid instrument, taken post-treatment or at any follow-up period.

Studies were excluded if they were not a RCT, if the primary intervention was a non-trauma-focused intervention, or if the primary outcome was another mental health condition, including PTSD. As the focus of our study was individuals with depression outside a PTSD diagnosis, participants in the studies were not required to have a history of trauma as defined by the major diagnostic criterion [i. e. 11, 12]. However, studies with an inclusion criterion of adverse or traumatic experiences, that specified a broad definition of adversities to include incidents such as neglect, parental divorce, or bullying, were included in the analysis.

Using the software program Covidence (https://www.covidence.org/) to store and manage the identified studies, two authors (SD & SM) independently conducted the manual review of the papers using the above PICO, and the stated inclusion and exclusion criteria. Any discrepancies in the screening were discussed with a third researcher (CL) until consensus was reached. The data was then extracted from the included studies independently by two members of the research team (SD & SM).

Quality assessment

The quality of the included studies was evaluated using the Cochrane Collaboration’s risk of bias for randomised studies tool [35]. As it is not possible for those delivering or receiving the intervention to be blind to the treatment, three other criteria were also assessed, as has been done by other researchers in other reviews of psychological interventions [36]. These criteria evaluated therapeutic allegiance, treatment fidelity and therapist qualifications. Studies were rated as low or high risk of bias or some concern. Assessment was conducted independently by two members of the research team (CL and SD). Any discrepancies were discussed together with the third author (SM) until a consensus was met.

Meta-analytic procedure

The impact of the TFTs on depressive symptoms was compared with all control conditions, including active psychological treatments and waitlist or non-psychological care. A pooled controlled condition has been used in other meta-analyses looking at depression across varied populations [36, 37]. Analysis of variable change from baseline was conducted using post-treatment and follow-up results, from continuous and dichotomous outcomes. For studies that involved multiple variables, such as active control and inactive control, or two measures of depression, the mean of both variables was used unless otherwise stated.

The software program Comprehensive Meta Analysis (Version 3) was used to calculate the pooled effect size of all relevant studies [38]. Effect sizes (Cohen’s d) of .8 can be considered large, .5 moderate and .2 small [39]. The studies were expected to vary in terms of number of sessions, type of TFT and the clinical severity of the participants; therefore, a random-effects model was used in all analyses [40]. An exception to this was if the number of studies was less than five, in which case fixed effects were used in line with current recommendations [40]. Heterogeneity was assessed using the i² statistic in which 25% refers to low, 50% to moderate and 75% to high heterogeneity [41, 42].

Subgroup and sensitivity analysis

Subgroup analyses were conducted to see if there was a difference between active and inactive control conditions, and to investigate the efficacy of TFTs when delivered as a standalone therapy (with no other psychological intervention) and as an adjunct to other psychotherapy. In addition, sensitivity analyses were conducted, removing any significant outliers. As EMDR was the TFT used in all but one study, an additional analysis was conducted, including only EMDR studies. A baseline to follow-up analysis was also conducted on studies where follow-up data was available.

Publication bias

The likelihood of a publication bias was assessed using Egger’s regression intercept test and a funnel plot. As no publication bias was detected Duval and Tweedies trim and fill procedure was not used.

Results

Search results

As shown in Fig 1, 751 studies were identified in the initial search, including 372 duplicates which were removed. Abstracts and titles of the remaining 379 studies were screened. This resulted in the exclusion of 354 papers. Studies that were excluded were tagged with the reason for exclusion. Studies were excluded primarily if a non-randomised trial design was used, the treatment provided was not a TFT, the participants in the study were required to have a PTSD diagnosis or a related traumatic experience, a primary diagnosis of another mental health disorder was an inclusion criterion, and finally, if complete study data could not be obtained. Data was considered as unavailable only after an attempt to contact the study authors did not result in the data being obtained. This was the case for two studies. In one study, the data was not accessible, as it was not available in English [43]. In another, results could not be sourced, despite being recorded in the trial register [44]. The majority of papers (n = 304) were excluded because PTSD was the primary focus or an inclusion criterion. The full text screening of the remaining papers (n = 25) was conducted, which resulted in 14 papers being excluded (see Fig 1). Following this, 11 studies, which involved a total of 567 participants, were considered eligible and included in the analysis.

Characteristics of included studies

Eight studies were published in peer-reviewed journals and three were unpublished dissertation theses, with one of these being published after the search was conducted. One unpublished paper was written in 2001, and the rest of the studies were published or written between 2015 to 2020.

All of the studies included adult participants. As shown in Table 1, seven were conducted on depressed patients in general, three studies were conducted on patients with comorbid medical difficulties, and one study treated individuals who were caregivers of an individual with dementia. Three studies had the TFT delivered as an adjunct to other psychological treatments, while the remaining eight received the intervention as a standalone psychological treatment. With the exception of one study [57], which examined a group intervention, all participants in the other included studies received their intervention individually. One study investigated the effectiveness of self-guided ImRs in a brief and long form compared with a waitlist [31], and the remaining studies used EMDR as the TFT. In the ImRs study, the intervention was self-administered, and the number of therapy sessions was not recorded. For the remaining trials number of TFT sessions in the studies’ designs ranged from 1 to 18 (average 6.5) and were between 45 to 120 minutes in duration. All studies used self-report measurements and one also used a structured clinical interview. The most common outcome measure used was the Beck Depression Inventory, Second Edition (BDI II) (seven studies). Of the 11 papers, four trials compared a TFT to an active psychological intervention and eight compared it to an inactive, or non-psychological intervention. One study had both active and inactive control conditions. Four studies measured depressive symptoms at follow-up periods ranging from 1 to 6 months post-treatment.

Table 1. Description of included studies.

Study	Interventions	n	TFT sessions and delivery	Population	Target	Measure	Time point	Dropouts	Overall risk of bias
Behnammoghadam et al., 2015 [45]	EMDR vs UC	60	3 x 45–90 min on alternate days; standalone	Cardiac patients with BDI II score >17, Iran	Experiences relating to cardiac arrests	BDI II	Post	Not reported	High risk
Dominguez et al., 2020 [46]	TAU + EMDR vs assertiveness (CBT) + TAU vs TAU	49	3 x 90 min; adjunct	Clinical and subclinical depression, Australia	Past aversive events, episodic in nature and thematically linked to current symptoms	SCID 5; DASS 42	Post; 6 and 12 weeks	9%	Low risk
Gauhar & Wajid, 2016 [54]	EMDR vs WL	17	6–8 weekly session 60 min; standalone	Clinical MDD diagnosis (DSM IV TR), Pakistan	Past aversive events, episodic in nature and thematically linked to current symptoms	BDI II	Post	35%	Some risk
Hase et al., 2018 [47]	EMDR + TAU vs TAU	30	4–12 (1–2 per week); adjunct	Psychiatric inpatients (diagnostic interview and BDI-II >12), Germany	Past aversive events, episodic in nature and thematically linked to current symptoms	BDI II SCL 90-R	Post	Not reported	High risk
Hogan, 2001 [48]	EMDR + TAU vs CBT +TAU	30	1 x 60 min; adjunct	Mood disorder or adjustment disorder with depressed mood, USA	Past aversive events, episodic in nature and thematically linked to current symptoms	BDI II	Post	Not reported	High risk
Kao et al., 2018 [55]	EMDR vs UC	57	4 x 60–90 min weekly; standalone	Patients with heart failure, Taiwan	Most unpleasant experience of heart failure	BDI II	Post; 1 & 3 months	9%	High risk
Moritz et al., 2018 [31]	Self guided ImRs (brief and long form) vs WL	127	Self administered over 6 weeks; standalone	Clinical, Germany	Past aversive events, episodic in nature and thematically linked to current symptoms	BDI II	Post	21%	Some risk
Study	Interventions	n	TFT sessions and delivery	Population	Target	Measure	Time point	Dropouts	Study quality
Ostacoli et al., 2018 [56]	EMDR vs CBT	66	15 +/-3; standalones	Treatment resistant depression (BDI >13 and MINI), Italy and Spain	Past aversive events, episodic in nature and thematically linked to current symptoms	BDI II	Post; 6 months	20%	Some risk
Passoni et al., 2018 [57]	EMDR vs WL (delayed treatment)	33	8 group x 120 min over two months; standalone	Primary Carers of dementia patients, Italy	Issues related to caring for dementia	AD-R	Post	25%	High risk
Rahimi et al., 2018 [58]	EMDR vs UC	90	6 x 30–45 min 3 sessions per week; standalone	Patients receiving haemodialysis with HADS score in borderline or clinical range, Iran	Traumatic haemodialysis scene	HADS	Post	0%	High risk
Su, 2018 [59]	EMDR vs CBT	8	10; standalone	Diagnosis of depression, USA	Past aversive events, episodic in nature and thematically linked to current symptoms	PHQ-9	1 month	0%	Some risk

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n = number analysed; EMDR = eye movement desensitisation and reprocessing; UC = usual care; BDI II = Beck Depression Inventory, Second Edition; TAU = treatment as usual; CBT = non trauma-focused cognitive behavioural therapy; SCID 5 = Structured Clinical Interview for DSM 5; DASS 42; Depression, Anxiety and Stress Scale– 42; ITT = intent to treat; WL = waitlist; MDD = major depressive disorder; DSM IV = Diagnostic and Statistical Manual, Fourth Edition; SCL 90-R Symptom Checklist–90-Revised; ImRs = imagery rescripting; MINI = Mini-International Neuropsychiatric Interview; AD-R = Anxiety and Depression Scale–Reduced Form; HADS = Hospital Anxiety and Depression Scale; PHQ-9 = Patient Health Questionnaire– 9.

Quality of included trials

Results of the quality analysis are presented in Tables 1 and 2. Of the 11 studies, one was rated as low risk of bias, six were rated as being high, and four were rated at some risk. All studies reported at least some risk of bias with regard to deviations from the intended interventions as neither the therapist nor client could be blind to the treatment condition. Further, all but one study was rated as some risk bias regarding the measurement of the outcome as they relied only on self-report data. Dropout numbers ranged from 0% to 35%, with two studies not reporting the attrition rates.

Table 2. Quality assessment: Risk of bias.

	Behnammoghadam et al., 2015 [45]	Dominguez et al., 2020 [46]	Gauhar & Wajid, 2016 [54]	Hase et al, 2018 [47]	Hogan, 2001 [48]	Kao et al., 2018 [55]	Moritz et al., 2018 [31]	Ostacoli et al., 2018 [56]	Passoni, 2018 [57]	Rahimi, 2018 [58]	Su, 2018 [59]
Bias arising from the randomisation process	-	+	?	+	?	?	+	+	?	?	?
Bias due to deviations from the intended interventions	-	?	?	?	-	?	?	?	?	?	?
Bias due to missing outcome data	-	+	?	-	-	?	+	?	+	+	+
Bias in the measurement of the outcome	?	+	?	?	?	?	?	?	?	?	?
Bias in the selection of the reported results	+	+	+	+	+	+	+	+	+	+	+
Therapist allegiance	-	+	-	-	?	-	NA	?	-	-	?
Treatment fidelity	-	+	+	-	?	?	?	?	-	-	+
Therapist qualifications	-	+	+	-	?	-	NA	+	-	-	?
Overall bias	-	+	?	-	-	-	?	?	-	-	?

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+ = low risk of bias;— = high risk of bias;? = some risk of bias; NA = Not applicable due to self-administered intervention.

Effect of TFTs at post-assessment

Summary results of all meta-analyses are shown in Table 3. Of the 11 studies, one did not report post-treatment data (follow-up data only). The remaining ten studies investigated the difference between a TFT and a control condition post-treatment totaling 559 participants. Two studies had three treatment groups, and two used two measures to assess depressive symptoms. As shown in Fig 2. the mean effect size was large [d = 1.17 (95% CI: 0.58~ 1.75)]. Heterogeneity was high (i² = 88.65). As one study appeared to be a significant outlier [45] we also conducted the analysis with this study removed (n = 499). This resulted in an improvement in heterogeneity (i² = 66.24) and precision (95% CI: 0.48~ 1.17). While effect size decreased, it was still large (d = 0.83).

Table 3. Meta-analysis of studies comparing the effects of trauma-focused treatments on depression.

Study		N _analysed	D	95% CI	I²
Post analysis
Studies with EMDR only	Random effects	432	1.29	0.67~1.91	87.60
Studies with EMDR only without outlier	Random effects	372	0.93	0.61~ 1.25	50.33
Active control comparison (CBT) only	Fixed effects	129	0.66	0.31~ 1.02	0
Follow-up data	Fixed effects	180	0.71	0.38~ 1.04	0

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Further analysis examined the post-assessment results for the nine studies that included only EMDR and a non-trauma focused control condition (n = 432). Analysis showed a large effect size [d = 1.29 (95% CI: 0.67 ~ 1.91)], and high heterogeneity (i² = 87.60). When the outlier was removed (n = 372) heterogeneity was moderate (i² = 50.33) and the effect size was still large [d = 0.93 (95% CI: 0.61~ 1.25)].

Subgroup analysis at post-assessment

The first subgroup analysis compared active and inactive control conditions (Fig 3). Due to one study having both an active and inactive control, multiple treatment groups were considered independently for the purpose of this analysis. All three trials that compared a TFT to an active control used EMDR as the TFT and CBT (non-trauma-focused) as the active control intervention (n = 129). The mean effect size of this analysis was moderate [d = 0.66 (95% CI: 0.31~ 1.02)] with zero heterogeneity in favour of the TFT. Of the eight studies (n = 446) that compared a TFT to inactive control, one used ImRs as the TFT and the remaining seven used EMDR. The mean effect size was large [d = 1.19 (95% CI: 0.53~ 1.86)] and heterogeneity was considerable (i² = 90.95). Analysis with the identified outlier removed resulted in an improvement in heterogeneity (i² = 73.48) and precision (95% CI: 0.62~ 1.06). While the effect size decreased, it was still large (d = 0.84).

Analyses of intervention delivery comparing standalone and adjunct treatments are presented in Fig 4. Three studies (n = 109) delivered the TFT as an adjunct to other psychotherapy, with EMDR being the TFT used in all trials. The adjunct psychotherapy used in two of these trials was delivered in groups and based on a CBT or psychodynamic model [46, 47], and one involved individual CBT [48]. Analysis of the results of these studies revealed in a moderate effect size [d = .49 (95% CI: 0.07~ 0.90)] with zero heterogeneity. Analysis of the TFT as a standalone intervention (n = 450) showed a larger effect size [d = 1.47 (95% CI: 0.70~ 2.25)] as well as an increase in heterogeneity (i² = 91.75).

Effects at follow-up

As shown in Table 2, four studies measured a total of 180 participants at follow-up, and all used EMDR as the TFT. For the two studies that used multiple follow-up assessments, analysis was conducted using the mean of these time points. The mean follow-up occurred at 11 weeks. The effect at follow-up was moderate [d = 0.71 (95% CI: 0.38~ 1.04)] with zero heterogeneity (Fig 5). The analysis was also calculated using the last follow-up measure in these studies. This resulted in a mean time of 13 weeks and the results were similar [d = .71 (95% CI: 0.38~1.05), (i² = 0)].

Publication bias

Publication bias was evaluated for the main analysis. As shown in Fig 6, visual analysis of the funnel plot highlights that three studies reported effect sizes outside the expected area, with two larger than expected and one smaller. One study with a larger effect size had been identified earlier as an outlier [45]. As discussed above, the removal of this study did not significantly alter the outcome of the analysis. An analysis using Egger’s regression intercept approach indicated no significant evidence of publication bias (t = 1.54; p = .16).

Discussion

The current meta-analysis was conducted to assess the effect of trauma-focused treatments (TFTs) for individuals with symptoms of depression as a primary presenting concern. Of the 11 studies identified to meet the inclusion criteria, ten used eye movement desensitisation and reprocessing (EMDR) as the TFT and one used imagery rescripting (ImRs). Therefore, caution should be exercised in generalising the results of this paper for interventions other than EMDR. The results of analysis of all eleven studies support the use of these interventions for individuals with depression. Data show a large effect size when looking at pre-post comparisons across ten studies (EMDR and ImRs) when compared with any other (active or non-active) condition, even when a significant outlier was removed. Analysis of the EMDR studies on pre-post treatment change for individuals with depression again shows a large effect with or without an outlier included in the analysis. Moreover, it appears that the effects of EMDR on depression measures are sustained even after treatment has ended. Four studies evaluated the ongoing impact of EMDR in follow-up periods from 1 to 6 months. The treatment effect size was moderate for this period of time. Analysis of the funnel plot was not consistent with any significant publication bias.

Based on eight studies, the effect size was large when TFTs (EMDR and ImRs) were compared with an inactive control. Of the three studies that used an active control, all used EMDR for the TFT and non-trauma-focused CBT as the active control. Analysis of EMDR compared with CBT showed that EMDR was more likely to decrease depressive symptoms than CBT post-treatment, with a moderate effect. This is important as, although CBT is recommended as the first-line psychological treatment for depression, it does not result in the desired symptom reduction for all individuals. Therefore, the evidence that there is an additional psychological intervention that is at least as effective as CBT but possibly targets different mechanisms or maintaining factors, such as intrusive memories, is welcomed.

Three studies investigated the effect off TFTs (EMDR) when delivered as an adjunct to other psychotherapy, and the remainder investigated the effect of TFTs (EMDR and ImRs) as a standalone psychological intervention. Both modes of intervention were shown to be effective in decreasing depressive symptoms when compared with control conditions with moderate and large effect size, respectively.

One of the core implications of this study is to underscore the importance of broadening of the definition of an event that is traumatic beyond the type of trauma needed for PTSD, and the use of TFTs to target these adversities. This includes experiences that are considered less severe such as bullying or relationship breakups, or adversities of omission, such as neglect. In the majority of the studies, the authors reported that the memories chosen to treat were subjectively distressing for the participant and linked thematically to the participants’ current difficulties in terms of either content, affect or cognitions. The focus on adverse events as aetiologically related to current psychopathology is central to schema therapy [49]. In schema theory the experiences of having core needs not met are viewed as the basis of what Young [49] called early maladaptive schemas that then cause dysfunction throughout the person’s life. In schema therapy, these adverse experiences are targeted with interventions such as ImRs, chair work, or EMDR [50].

The paucity of RCTs using interventions other than EMDR was surprising to the authors. There was one paper that was initially included in the study that examined the efficacy of TF CBT vs EMDR; however, this was excluded as there was no non trauma-focused control condition [30]. This deficit is particularly unexpected due to the diverse body of literature supporting other TFTs [28, 34, 51], including a recent book dedicated to the practise of imagery and ImRs for treating depression and bipolar disorder [52]. Accordingly, further RCTs, including multi-arm head to head studies comparing various TFTs with a control condition, are needed. In addition to efficacy studies, process studies on how different components of other TFTs, such as cognitive restructuring or behavioural change, effect variables found to mediate depression severity such as avoidance and rumination [18] could further build on our ability to understand the aetiology and maintenance of depressive disorders.

The heterogeneity of several analyses was large in this study. This is consistent with other meta-analyses of treatments for depression [53]. These might be due to the methodological variation mentioned above or the diversity of presentations that can occur in individuals with depressive symptoms. Further, this may reflect the diversity in intervention delivery and control conditions. However, despite this diversity, in some of the analyses, the heterogeneity was satisfactory. For example, after removing outliers, the effect of EMDR compared with a non-trauma-focussed controlled condition was large, even though heterogeneity was moderate. This was somewhat surprising given that the EMDR treatment protocols used across these studies varied, as were the session duration and intensity, and the nature of the samples. Thus, care needs to be taken when interpreting these findings, especially as the results presented in these analyses are mainly based on self-report data. Accordingly, it would be useful to conduct further research with multi-site studies, using similar protocols, clinician administered assessment and similar samples to increase the certainty of these findings.

The current study highlighted the substantial symptom reduction experienced for people with depression diagnosis or depressive symptoms following TFTs targeting negative memories related to current symptomology. Of the studies included in this analysis none involved a formal assessment for PTSD to allow for the exclusion of those with a comorbid diagnosis. Although most studies that described the memories targeted in the TFT treatment condition would not meet the PTSD severity criteria, future studies assessing and excluding individuals with a PTSD diagnosis are needed to increase the confidence in the assertion that the TFT can be effective in decreasing mood outside a PTSD diagnosis.

There are several other limitations in the current study. In addition to only one non-EMDR study, only one paper evaluated two different active treatment modes. Therefore, the generalisability of the conclusions in the meta-analyses beyond EMDR or the comparative efficacy of TFTs remains to be established. Most studies used inactive controls, and those that did use active controls only used non-trauma-focused CBT. Accordingly, the added advantage of a TFT in general beyond non-trauma-focused CBT for depression cannot be ascertained from this study.

Although we limited our review to studies that used RCTs, there was a diversity in methodical rigour in the designs of the included studies, with several studies rated as having a high risk of bias. For example, several of the studies in the analysis involved relatively small samples. Further, only one study used an observer-rated clinical interview to measure change in depression diagnosis, the other ten assessed symptom change with self-report inventories. Future high-quality studies evaluating the efficacy of a range of different TFTs compared with a range of controls with outcomes, including structured clinical interviews, are needed.

To conclude, the results of this meta-analysis support the use of EMDR as a promising approach for treating depressive symptoms. There were not enough RCTs to make the same recommendation about TFTs in general. Further studies looking at a range of TFTs (including EMDR), with increased methodological rigour and larger sample sizes, would increase the confidence in these conclusions.

Supporting information

S1 Checklist. PRISMA 2009 checklist.

(DOC)

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Acknowledgments

The authors would like to thank the authors of the cited papers for responding to their queries.

Data Availability

The complete search strategy is detailed in the section with the subheading search strategy in the manuscript and the articles found and analysed are detailed in Table 1.

Funding Statement

The authors received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0254778.r001

Decision Letter 0

Andrea Martinuzzi

17 Feb 2021

PONE-D-20-24791

Trauma Focused Treatments for Depression. A Systematic Review and Meta-Analysis

PLOS ONE

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Reviewer #1: Thank you for the opportunity to review this manuscript reviewing trauma-focused treatments for depression. While I think the intention of the review would be of interest to readers, the frame of "trauma-focused treatments" seems misleading (discussed below). The authors conclude that EMDR would be a beneficial treatment for depression. This should be emphasized and conjectures about the use of TFTs more broadly should be removed, especially in the discussion section. Generally, highlighting in the introduction mechanisms of change underlying various TFTs will be important to add, as this provides theoretical rationale for why these treatments might be beneficial for individuals suffering from depression. In the discussion, discussing why EMDR is the only TFT used for depression in the studies reviewed is also important to examine further. Overall, this paper makes a contribution to the field, but significant changes/additions to the introduction and discussion are needed.

Introduction

Please provide peer-reviewed citations for the benefits of trauma-focused treatments for depression. Citing ISTSS does not support the suggestion that benefits of TFT for depression are well-documented.

Please fix this sentence accordingly: “An increasing number of clinical trials have been conducted investigating a range of TFTs (exposure-based cognitive therapy, EMDR, trauma-focused-CBT, and imagery rescripting) as treatments for depression.”

The following sentence is wordy and difficult to follow – please revise to something like, “Following the increase in published studies examining TFT for depression, a number of narrative reviews have been published highlighting the promise of such interventions.”

The introduction would benefit from more detailed examination of previous studies looking at TFTs for depression. What are the mechanisms of change seen across studies with different treatments? Moreover, while adverse childhood experiences are associated with depression, what factors lead to a primary diagnosis of depression over PTSD in these cases and how might this account for benefits from TFT treatment for depressed individuals? If individuals suffering from depression did not experience a significant adverse event precipitating symptom onset, would they derive the same benefits from TFTs? The intro is substantially lacking and more examination of these questions is warranted.

Method

Were individuals with co-morbid diagnoses of PTSD and depression considered?

This sentence is wordy and difficult to follow. Please consider revising…“Studies with an inclusion criterion of adverse or traumatic events, including neglect or other incidents that would fall outside of the DSM 5 diagnostic criteria for PTSD, were not excluded from the analysis.”

Please fix this sentence accordingly: “Analysis from baseline was conducted using post-treatment and at follow-up results, from continuous and dichotomous outcomes.”

Results

Please fix this sentence accordingly: “As shown in Fig 1, 751 studies were initially identified, and 372 duplicates were removed.”

Please fix this sentence accordingly: “A total of 11 studies with a sum of 567 participants were eligible for analysis.”

Is there utility in keeping the study investigating rescripting given that the remaining studies used EMDR? Moreover, given that all studies (with one exception) used EMDR rather than other trauma-focused treatments, is it possible that this speaks to the fact that trauma treatments are not necessarily beneficial for depression but treatments aimed at alleviating distress/processing negative memories are beneficial. It seems that other trauma therapies (i.e., CPT, exposure therapy, TF-CBT) emphasize exposure/cognitive restructuring/behavioral change whereas EMDR is focused on memory reconsolidation.

Was the analysis of EMDR vs. CBT looking specifically at behavioral activation or a general CBT model? Given that BA is an intended treatment for depression, this would be an important distinction.

Discussion

The general conclusion drawn from this meta-analysis is misleading – TFTs are not necessarily a promising approach to treating depressive symptoms. EMDR may be a promising approach, according to findings. Overall, the discussion would benefit from exploration of mechanisms of change underlying EMDR for depression, and some mention of why other TFT have not been used solely for depression.

General

Please read through the manuscript from grammatical errors.

Reviewer #2: This manuscript aims to provide a meta-analysis of studies using trauma-focused treatments to treat depression without a diagnosis of PTSD. Given that there are now 11 such studies it is worthwhile to summarize them. It seems to me that this paper would be more helpful with a bit more of a critique of the existing literature and attention to the question of why such treatments may be helpful.

Introduction:

The introduction is well-written and clear.

I wonder if the last sentence of the first paragraph is misleading – is the high rate of relapse an indictment of the treatments or just a commentary on the episodic nature of the illness?

Perhaps for this sentence specify that these trials have examined TFTs as stand-alone treatments specifically for depression: “An increasing number of clinical trials have been conducted investigating a range of TFTs (exposure-based cognitive therapy, EMDR, trauma-focused-CBT, and imagery rescripting) as a treatment for depression”

For the second paragraph, the authors discuss targeting the intrusive thoughts – but TFT’s target much more broadly the symptoms of PTSD (especially avoidance for some of them).

Perhaps use more specific and less colloquial language: “This was done via a systematic review of all randomised controlled trials and a meta-analysis of the pooled data to get an understanding of the overall state of the scientific evidence.” i.e. what exactly are the aims or hypotheses?

Methods:

The methods section appears reasonable.

Whether or not studies requiring a trauma were excluded is not clear.

It is unclear to me why non-clinical populations would be included in these studies? “The populations sampled were expected to be varied including clinical and non-clinical populations”

Results:

Is there an extra comma here? “751, studies were initially identified”

It is somewhat unclear to me if studies were excluded for requiring a trauma experience (different information in methods vs. results). This doesn’t seem to me like it would be a problem. If there is no trauma experience, then what would be the rationale for using a TFT?

For the studies where the TFT was an adjunct, what was the primary treatment?

The range of sessions is given (1 to 18), but perhaps a mean would also be helpful. I had to look at the tables to determine that the 1-session treatment is by design and not simply due to dropout; a one-session TFT seems qualitatively different than most substantive TFTs.

This seems hard to believe: “All three trials that compared TFT to an active control used EMDR as the TFT and CBT (non-trauma-focused) as the active control intervention (n = 129). The mean effect size of this analysis was moderate [d = 0.66 (95% CI: 0.31� 1.02)] with zero heterogeneity in favour of the TFT.” Was there an allegiance effect in these studies? How to explain this?

Did any of the studies report on PTSD symptoms (in the absence of a PTSD diagnosis)? In the discussion the authors note that these changes are seen “outside of a PTSD diagnosis” – I think one question is whether these patients may have had an (undiagnosed) PTSD diagnosis or symptoms.

Discussion:

Change “deigns” to designs.

I don’t think this sentence is supported by the available evidence: “Therefore, the evidence that there is an additional psychological intervention that is at least as effective as CBT but possibly targets different mechanisms or processes is welcomed.”

Overall, the discussion seems to be mostly a review of the results with little interpretation.

As a future direction, it would seem to me that it would be useful to test whether there are certain sub-populations that respond better to TFT. One would imagine that these would be most useful for those for whom an adverse event/trauma is part of the etiological picture of depression – otherwise it is theoretically unclear why a TFT would be used. Indeed, I would like to see the authors address this question in the discussion of why a TFT should indeed be expected to have an effect on depression in the absence of PTSD. What might be the mechanisms of treatment? Why would one choose a TFT over another front-line treatment for depression? Why use a TFT versus something like schema therapy or an approach that is geared toward adversities rather than traumas per se? If more rigorous studies found similar results to these, what would that tell us about the etiology of depression? Or about trans-diagnostic mechanisms of change in treatment? Or the overlap among stressful-event and trauma-related symptoms?

It is notable that EMDR was the TFT in all but one study. Why might that be? Is it perhaps that it is the least “trauma-focused” of the TFT’s? Prolonged exposure would entail a significant amount of time addressing the trauma itself, and Cognitive Processing Therapy has significant overlap with cognitive therapy for depression.

It is also notable that bias rates are quite high for this group of studies (along with small samples and almost universal self-report measures), which dampens my enthusiasm (or at least trust in) the results, and I think should be further highlighted as a limitation – not of the paper but of the literature.

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Reviewer #2: No

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PLoS One. 2021 Jul 22;16(7):e0254778. doi: 10.1371/journal.pone.0254778.r002

Author response to Decision Letter 0

28 Apr 2021

Response to Reviewers

Thank you for taking the time to review our article "Trauma Focused Treatments for Depression. A Systematic Review and Meta-Analysis". We are grateful for the feedback provided and believe that this has substantially improved the quality of our paper. We have responded to these comments below and attached an updated manuscript highlighting changes made and responding to the specific points raised.

1. This should be emphasized and conjectures about the use of TFTs more broadly should be removed, especially in the discussion section.

Thank you, this is an important point, and we have considered it in detail. When we set out to do the review, we aimed to look at TFTs in general. We were aware of clinicians/ researchers from different approaches to trauma treatments advocating that TFTs for depression was efficacious (Hayes et al., 2007; Minelli et al., 2019; Moritz et al., 2018), including a book dedicated to imagery-based cognitive therapy on mood disorders in which in chapter 9 the authors advocate for imagery rescripting as a treatment for depression (Holmes, Hales, Young, & Di Simplicio, 2019). Thus, in registering our review with PROSPERO we stated what we intended to search, which is TFTs in all shapes and forms. Therefore, we believed it would not be objective scientific reporting to change the paper's title. Our rationale was to look at TFTs in general. We found that despite several outcome studies using TFTs for depression, there was a dearth of TFTs other than EMDR being tested using RCT designs. We agree with the reviewer that this is a significant point and important to make clear in the manuscript. Thus, we have articulated this story in the revised manuscript and discussed the need to have more RCTs on TFTs other than EMDR to further test the hypothesis.

2. Generally, highlighting in the introduction mechanisms of change underlying various TFTs will be important to add, as this provides theoretical rationale for why these treatments might be beneficial for individuals suffering from depression.

We have expanded the introduction to highlight the role of adverse events in predisposing individuals to depression and the high frequency of intrusive memories for depressed individuals. We also hypothesise the role of these experiences and related intrusions in maintenance for ongoing depression.

3. In the discussion, discussing why EMDR is the only TFT used for depression in the studies reviewed is also important to examine further. Overall, this paper makes a contribution to the field, but significant changes/additions to the introduction and discussion are needed.

Thank you for this comment. Yes, we were surprised that only one study of the 11 RCTs was not EMDR using our criteria. This is particularly surprising as most PTSD treatments are as effective at decreasing comorbid depression symptoms as they are at decreasing PTSD symptoms (Ronconi et al 2015). Also, there are several non-randomised outcome studies that have shown support for TFTs in patients with depression. These include cognitive therapy (Hayes et al., 2007), trauma-focused-CBT (Minelli et al., 2019) and a variety for imagery rescripting (Wheatley & Hackmann, 2011). In the revised manuscript, we have added additional text to the introduction as to why it makes sense to assess the evidence for TFTs in depression which draws on the role of aversive events and intrusive memories. We continue this in the discussion and include refences to schema therapy (as suggested by the other reviewers) to further provide a conceptual model that supports why TFTs for depression would be beneficial.

4. Please provide peer-reviewed citations for the benefits of trauma-focused treatments for depression. Citing ISTSS does not support the suggestion that benefits of TFT for depression are well-documented.

Thank you for your comment. We have taken this on board and added additional references. These are Ehring et al., 2014; International Society of Traumatic Stress Studies, 2019; Lenz & Hollenbaugh, 2015; and Ronconi, Shiner, & Watts, 2015.

5. Please fix this sentence accordingly: "An increasing number of clinical trials have been conducted investigating a range of TFTs (exposure-based cognitive therapy, EMDR, trauma-focused-CBT, and imagery rescripting) as treatments for depression."

Thank you. We have altered the sentence, and it now reads: "An increasing number of clinical trials have been conducted investigating a range of TFTs as a treatment for depression outside a PTSD diagnosis, including exposure-based cognitive therapy (Hayes et al., 2007), EMDR (Hase et al., 2015), trauma-focused-CBT (Minelli et al., 2019), and imagery rescripting (Moritz et al., 2018)".

6. The following sentence is wordy and difficult to follow – please revise to something like, "Following the increase in published studies examining TFT for depression, a number of narrative reviews have been published highlighting the promise of such interventions."

We have revised this sentence. It is now: "Due to the number of published manuscripts relating to using a TFT for depression, narrative reviews of both EMDR (Carletto et al., 2017; Malandrone, Carletto, Hase, Hofmann, & Ostacoli, 2019) and imagery rescripting (Wheatley & Hackmann, 2011) have been published. These reviews highlight that each TFT has been found to be effective with depressed individuals in the absence of any specific PTSD type trauma background".

7. The introduction would benefit from more detailed examination of previous studies looking at TFTs for depression. What are the mechanisms of change seen across studies with different treatments? Moreover, while adverse childhood experiences are associated with depression, what factors lead to a primary diagnosis of depression over PTSD in these cases and how might this account for benefits from TFT treatment for depressed individuals? If individuals suffering from depression did not experience a significant adverse event precipitating symptom onset, would they derive the same benefits from TFTs? The intro is substantially lacking and more examination of these questions is warranted.

Thank you for your comments. We have elaborated on why TFTs may be of benefit for depression in the introduction.

We have also made the steps of reasoning easy to follow in the introduction. That is:

i. Adverse life events are very common in depression and correlate with poor treatment response and symptom chronicity.

ii. People with depression have intrusive memories of such experiences, almost as common as people with PTSD.

iii. Many adverse events fail to make criterion A for PTSD, e.g. emotional abuse, life-threatening illness (specifically excluded in DSM 5), neglect, and bullying.

iv. There are theoretical reasons as to why intrusive memories might account for depression.

Further, we discuss that many aversive events are not sufficient to give rise to a PTSD diagnosis including eg bullying, parental abandonment, and neglect. Nevertheless, these can be experienced as traumatic and hence can benefit from a trauma-based approach.

Method

8. Were individuals with comorbid diagnoses of PTSD and depression considered?

While the inclusion of individuals with comorbid PTSD was considered, there is already substantial evidence to highlight the efficacy of TFTs on depression for these individuals (Ehring et al., 2014; International Society of Traumatic Stress Studies, 2019; Lenz & Hollenbaugh, 2015; Ronconi, Shiner, & Watts, 2015). We have added further references in the introduction to reflect this evidence. However, our focus was to look at individuals who do not have PTSD to assess if TFTs are helpful for depressive symptoms outside the PTSD diagnosis, and thus we limited the inclusion criteria to these studies.

9. This sentence is wordy and difficult to follow. Please consider revising… "Studies with an inclusion criterion of adverse or traumatic events, including neglect or other incidents that would fall outside of the DSM 5 diagnostic criteria for PTSD, were not excluded from the analysis."

We have reworded this sentence and the one prior and given several examples for clarity. It now reads: "As the focus of our study was individuals with depression outside a PTSD diagnosis participants in the studies were not required to have a history of trauma as defined by the major diagnostic criterion (i. e. American Psychiatric Association, 2013; World Health Organisation, 2018). However, studies with an inclusion criterion of adverse or traumatic experiences that specified a broad definition of adversities to include incidents such as neglect, parental divorce, or bullying, were included in the analysis."

10. Please fix this sentence accordingly: "Analysis from baseline was conducted using post-treatment and at follow-up results, from continuous and dichotomous outcomes."

Thank you. We have altered the sentence to now reads: "Analysis of variable change from baseline was conducted using post-treatment and at follow-up results, from continuous and dichotomous outcomes."

Results

11. Please fix this sentence accordingly: "As shown in Fig 1, 751 studies were initially identified, and 372 duplicates were removed."

We have altered this sentence for clarity to: "As shown in Fig 1, 751 studies were identified in the initial search, including 372 duplicates which were removed."

12. Please fix this sentence accordingly: "A total of 11 studies with a sum of 567 participants were eligible for analysis."

Thank you. This has been amended: "Following this, 11 studies, which involved a total of 567 participants, were considered eligible and included in the analysis."

13. Is there utility in keeping the study investigating rescripting given that the remaining studies used EMDR? Moreover, given that all studies (with one exception) used EMDR rather than other trauma-focused treatments, is it possible that this speaks to the fact that trauma treatments are not necessarily beneficial for depression but treatments aimed at alleviating distress/processing negative memories are beneficial. It seems that other trauma therapies (i.e., CPT, exposure therapy, TF-CBT) emphasize exposure/cognitive restructuring/behavioral change whereas EMDR is focused on memory reconsolidation.

Thank you. This is an important point. We agree that all trauma therapies aim to eventually alleviate the distress of negative memories (Schnyder et al., 2015). They differ on the type of exposure, the degree that they engage the client to focus on the recollection of the event, the meaning associated with the event, or the extent they directly target behaviour change. Prolonged exposure involves extensive retelling of the trauma experience and further exposure to these memories via listening to recordings of these sessions. Whilst there is diversity in opinion as to the active mechanisms of this treatment, habituation rather than memory reconsolidation has been emphasised in prolonged exposure in contrast to EMDR (Careaga, Girardi, & Suchecki, 2016). We do not think that it is the mechanism underlying the therapy that explains why so few studies met our inclusion criteria. In our view, if a treatment works on an intrusive memory of a negative event, the type of event (i.e. whether that memory is verbal bullying or a physical assault) is unlikely to make a difference. One possible reason for this has to do with the underlying theory. EMDR is taught within a theory of what Shapiro described as Adaptive Information Processing. Central to this theory is the idea that negative life events can lead to negative self-view or a negative sense of the world that can lead to psychopathology. It is not a theory of PTSD per se but, in essence, a transdiagnostic approach. Perhaps other TFT approaches have focused on PTSD symptoms, so clinicians and researchers have been less likely to consider investigating how their treatment works on non PTSD type traumas.

We acknowledge that our response to this point from the reviewer is speculative. Because of this we decided not to include these thoughts in the revised manuscript however we could include them if they were deemed to make a contribution.

14. Was the analysis of EMDR vs. CBT looking specifically at behavioral activation or a general CBT model? Given that BA is an intended treatment for depression, this would be an important distinction.

In the four studies that used CBT as a comparator, the intervention was labelled CBT by the writers. The interventions all included cognitive restructuring and behaviour homework tasks. None were purely behavioural activation.

Discussion

15. The general conclusion drawn from this meta-analysis is misleading – TFTs are not necessarily a promising approach to treating depressive symptoms. EMDR may be a promising approach, according to findings. Overall, the discussion would benefit from exploration of mechanisms of change underlying EMDR for depression, and some mention of why other TFT have not been used solely for depression.

Thank you for pointing this out. We certainly do not intend anything to be perceived as misleading. However, we do not agree with the comment that TFTs have not been used for depression when this is the sole issue. As discussed in point 5 above, TFTs have been used and advocated as treatments for depression, and we have provided the basis for this claim. In the revised manuscript, we have expanded the introduction and discussion to document this. However, our prescribed literature search meant that several outcome studies did not meet the inclusion criteria. In the discussion, we have been more circumspect about TFTs in general as applied to depression, given we only found the one non-EMDR RCT that met our criteria. We have identified this as a future research priority.

General

16. Please read through the manuscript from grammatical errors.

Thank you, this has been addressed.

Introduction:

1. The introduction is well-written and clear.

Thank you and noting your first comment we have expanded the introduction to address the question of why such treatments might be helpful.

2. I wonder if the last sentence of the first paragraph is misleading – is the high rate of relapse an indictment of the treatments or just a commentary on the episodic nature of the illness?

We have added the following additional sentence to clarify this. "Although these relapse rates may be a reflection of the episodic nature of the disorder (Kanter, Busch, Weeks, & Landes, 2008), further investigation into evidence based interventions is warranted."

3. Perhaps for this sentence specify that these trials have examined TFTs as stand-alone treatments specifically for depression: "An increasing number of clinical trials have been conducted investigating a range of TFTs (exposure-based cognitive therapy, EMDR, trauma-focused-CBT, and imagery rescripting) as a treatment for depression"

Thank you. We have altered this sentence. It now reads: "An increasing number of clinical trials have been conducted investigating a range of TFTs as a treatment for depression outside a PTSD diagnosis, including exposure-based cognitive therapy (Hayes et al., 2007), EMDR (Hase et al., 2015), trauma-focused-CBT (Minelli et al., 2019), and imagery rescripting (Moritz et al., 2018)."

4. For the second paragraph, the authors discuss targeting the intrusive thoughts – but TFT's target much more broadly the symptoms of PTSD (especially avoidance for some of them).

Thank you, we have altered the introduction to include experiential avoidance, intrusive images, and emotions.

5. Perhaps use more specific and less colloquial language: "This was done via a systematic review of all randomised controlled trials and a meta-analysis of the pooled data to get an understanding of the overall state of the scientific evidence." i.e. what exactly are the aims or hypotheses?

This has been altered. It now reads: "It was hypothesised that, for individuals with depression as their primary complaint, those who receive a TFTs would be more likely to show a decrease in depressive symptoms and increase the likelihood of remission than those who receive a control condition. This hypothesis was assessed via a systematic review of all relevant randomised controlled trials (RCTs) and a meta-analysis of the pooled data."

Methods:

6. The methods section appears reasonable.

Thank you.

7. Whether or not studies requiring a trauma were excluded is not clear.

We have elaborated on this point for clarity.

8. It is unclear to me why non-clinical populations would be included in these studies? "The populations sampled were expected to be varied including clinical and non-clinical populations".

Thank you for pointing this out. This was a misleading sentence. In the revised manuscript the sentence now reads: "The studies were expected to vary in terms of number of sessions, type of TFT and the clinical severity of the participants, therefore a random effects model was used in all analyses." The fact that one study only included a structured clinical interview is now discussed under limitations in the discussion.

Results:

9. Is there an extra comma here? "751, studies were initially identified"

Thank you, this has been removed.

10. It is somewhat unclear to me if studies were excluded for requiring a trauma experience (different information in methods vs. results). This doesn't seem to me like it would be a problem. If there is no trauma experience, then what would be the rationale for using a TFT?

We have made this more explicit in the introduction. A trauma experience does not have to be one that could potentially give rise to PTSD. One of the main tenants of this paper focuses on adverse events, which is a broader category. Such events include 'trauma of omissions' (not having core needs met such as emotional or physical neglect), abuse experiences that do not involve a threat to life, such as verbal abuse from a childhood carer or bullying from peers.

11. For the studies where the TFT was an adjunct, what was the primary treatment?

We have updated this in the results section. The adjunct psychotherapy used in two of these trials was delivered in groups and based on a CBT or psychodynamic model (Dominguez, Drummond, Gouldthorp, Janson, & Lee, 2020; Hase et al., 2018), and one involved individual CBT (Hogan, 2002).

12. The range of sessions is given (1 to 18), but perhaps a mean would also be helpful. I had to look at the tables to determine that the 1-session treatment is by design and not simply due to dropout; a one-session TFT seems qualitatively different than most substantive TFTs.

Thank you. We have amended the results to clarify the number of sessions described in the table as per the intervention design. We have also including the average number of sessions. It now reads: "In the imagery rescripting study the intervention was self-administered, and the number of therapy sessions were not recorded. For the remaining trials number of TFT sessions in the studies' designs ranged from 1 to 18 (average 6.5) and were between 45 to 120 minutes in duration."

13. This seems hard to believe: "All three trials that compared TFT to an active control used EMDR as the TFT and CBT (non-trauma-focused) as the active control intervention (n = 129). The mean effect size of this analysis was moderate [d = 0.66 (95% CI: 0.31~ 1.02)] with zero heterogeneity in favour of the TFT." Was there an allegiance effect in these studies? How to explain this?

This was a surprise to us as well. It may be impacted by the quality of the included studies as demonstrated in the risk of bias analysis, given two of the included studies had some or high risk of bias. However, as mentioned more generally in the discussion, most of the data in this analysis was self-report, which could influence results. Hopefully, these findings lead to further testing of the interventions.

14. Did any of the studies report on PTSD symptoms (in the absence of a PTSD diagnosis)? In the discussion the authors note that these changes are seen "outside of a PTSD diagnosis" – I think one question is whether these patients may have had an (undiagnosed) PTSD diagnosis or symptoms.

None of the studies specifically assessed for and excluded individuals with PTSD or reported on PTSD symptoms for all participants. This has been identified in the discussion and highlighted as an important area for future research.

Discussion:

15. Change "deigns" to designs.

This has been altered.

16. I don't think this sentence is supported by the available evidence: "Therefore, the evidence that there is an additional psychological intervention that is at least as effective as CBT but possibly targets different mechanisms or processes is welcomed."

We have altered this sentence. It now reads: "Therefore, the evidence that there is an additional psychological intervention that is at least as effective as CBT but possibly targets different mechanisms or maintaining factors, such as intrusive memories, is welcomed."

17. Overall, the discussion seems to be mostly a review of the results with little interpretation.

We have extended several key points in the discussion regarding the relevance and implications for future research and clinical practice.

18. As a future direction, it would seem to me that it would be useful to test whether there are certain sub-populations that respond better to TFT. One would imagine that these would be most useful for those for whom an adverse event/trauma is part of the etiological picture of depression – otherwise it is theoretically unclear why a TFT would be used. Indeed, I would like to see the authors address this question in the discussion of why a TFT should indeed be expected to have an effect on depression in the absence of PTSD. What might be the mechanisms of treatment? Why would one choose a TFT over another front-line treatment for depression? Why use a TFT versus something like schema therapy or an approach that is geared toward adversities rather than traumas per se? If more rigorous studies found similar results to these, what would that tell us about the etiology of depression? Or about trans-diagnostic mechanisms of change in treatment? Or the overlap among stressful-event and trauma-related symptoms?

Thank you for your comment. We have considerably altered the introduction to argue why TFTs would have an effect on depression. As described in point 7 of the other reviewers comments the argument is:

i. Adverse life events are very common in depression and correlate with poor treatment response and symptom chronicity.

ii. People with depression have intrusive memories of such experiences almost as frequently as people with PTSD.

iii. Many adverse events fail to make criterion A for PTSD, e.g. emotional abuse, life threatening illness (specifically excluded in DSM 5), neglect, and bullying.

iv. There are theoretical reasons as to why intrusive memories might account for depression.

In the discussion, we continue to examine these issues and further illustrate theories as to why TFTs are indicated for depression using schema therapy as you suggest. We added: "The focus on adverse events as aetiologically related to current psychopathology is central to schema therapy (Young, Klosko, & Weishaar, 2003). In schema theory the experiences of having core needs not met are viewed as the basis of what Young called early maladaptive schemas that then cause dysfunction throughout the person's life. In schema therapy these experiences are targeted with interventions such as imagery rescripting, chair work, or EMDR (Young, Zangwill, & Behary, 2002)."

19. It is notable that EMDR was the TFT in all but one study. Why might that be? Is it perhaps that it is the least "trauma-focused" of the TFT's? Prolonged exposure would entail a significant amount of time addressing the trauma itself, and Cognitive Processing Therapy has significant overlap with cognitive therapy for depression.

The fact that there was only one relevant non-EMDR RCT was a surprise to us and highlighted a significant gap in the literature as we identify in the discussion. One hypothesis is that several other TFTs, including prolonged exposure and cognitive processing therapy, have similar origins to many evidence-based depression treatments, coming from a cognitive or behavioural theoretical background. EMDR and imagery rescripting are both relatively new interventions and based on differing theoretical backgrounds. Thus, it may be considered that there is more interest in exploring the impact of these newer interventions, with varied theoretical background. However, this is purely speculation, and it is outside of the scope of this study to adequately address why past researchers have chosen to use particular interventions over others.

20. It is also notable that bias rates are quite high for this group of studies (along with small samples and almost universal self-report measures), which dampens my enthusiasm (or at least trust in) the results, and I think should be further highlighted as a limitation – not of the paper but of the literature.

Thank you, this seems valid. We have elaborated on this point in the discussion on page 20.

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5: Washington, DC: American psychiatric association.

Careaga, M. B. L., Girardi, C. E. N., & Suchecki, D. (2016). Understanding posttraumatic stress disorder through fear conditioning, extinction and reconsolidation. Neuroscience & Biobehavioral Reviews, 71, 48-57.

Carletto, S., Ostacoli, L., Colombi, N., Luca, C., Oliva, F., Isabel, F., & Arne, H. (2017). EMDR for depression: A systematic review of controlled studies.

Dominguez, S. K., Drummond, P., Gouldthorp, B., Janson, D., & Lee, C. W. (2020). A randomized controlled trial examining the impact of individual trauma‐focused therapy for individuals receiving group treatment for depression. Psychology and Psychotherapy: Theory, Research and Practice.

Ehring, T., Welboren, R., Morina, N., Wicherts, J. M., Freitag, J., & Emmelkamp, P. M. (2014). Meta-analysis of psychological treatments for posttraumatic stress disorder in adult survivors of childhood abuse. Clinical Psychology Review, 34(8), 645-657.

Hase, M., Balmaceda, U. M., Hase, A., Lehnung, M., Tumani, V., Huchzermeier, C., & Hofmann, A. (2015). Eye movement desensitization and reprocessing (EMDR) therapy in the treatment of depression: a matched pairs study in an inpatient setting. Brain and Behavior, 5(6).

Hase, M., Plagge, J., Hase, A., Braas, R., Ostacoli, L., Hofmann, A., & Huchzermeier, C. (2018). Eye movement desensitization and reprocessing versus treatment as usual in the treatment of depression: a randomized-controlled trial. Frontiers in psychology, 9.

Hayes, A. M., Feldman, G. C., Beevers, C. G., Laurenceau, J.-P., Cardaciotto, L., & Lewis-Smith, J. (2007). Discontinuities and cognitive changes in an exposure-based cognitive therapy for depression. Journal of consulting and clinical psychology, 75(3), 409.

Hogan, W. A. (2002). The comparative effects of eye movement desensitization and reprocessing (EMDR) and cognitive behavioral therapy (CBT) in the treatment of depression.

Holmes, E. A., Hales, S. A., Young, K., & Di Simplicio, M. (2019). Imagery-based cognitive therapy for bipolar disorder and mood instability: Guilford Publications.

International Society of Traumatic Stress Studies. (2019). Posttraumatic Stress Disorder. Prevention and Treatment Guidelines. Retrieved from www.istss.org/treating-trauma/new-istss-prevention-and-treatment-guidelines

Kanter, J. W., Busch, A. M., Weeks, C. E., & Landes, S. J. (2008). The nature of clinical depression: Symptoms, syndromes, and behavior analysis. The Behavior Analyst, 31(1), 1-21.

Lenz, A. S., & Hollenbaugh, K. M. (2015). Meta-analysis of trauma-focused cognitive behavioral therapy for treating PTSD and co-occurring depression among children and adolescents. Counseling Outcome Research and Evaluation, 6(1), 18-32.

Malandrone, F., Carletto, S., Hase, M., Hofmann, A., & Ostacoli, L. (2019). A brief narrative summary of randomized controlled trials investigating EMDR treatment of patients with depression. Journal of EMDR Practice and Research, 13(4), 302-306.

Minelli, A., Zampieri, E., Sacco, C., Bazzanella, R., Mezzetti, N., Tessari, E., . . . Bortolomasi, M. (2019). Clinical efficacy of trauma-focused psychotherapies in treatment-resistant depression (TRD) in-patients: A randomized, controlled pilot-study. Psychiatry Research, 273, 567-574. doi:http://dx.doi.org/10.1016/j.psychres.2019.01.070

Moritz, S., Ahlf-Schumacher, J., Hottenrott, B., Peter, U., Franck, S., Schnell, T., . . . Jelinek, L. (2018). We cannot change the past, but we can change its meaning. A randomized controlled trial on the effects of self-help imagery rescripting on depression. Behaviour Research and Therapy, 104, 74-83.

Ronconi, J. M., Shiner, B., & Watts, B. V. (2015). A meta-analysis of depressive symptom outcomes in randomized, controlled trials for PTSD. The Journal of nervous and mental disease, 203(7), 522-529.

Schnyder, U., Ehlers, A., Elbert, T., Foa, E. B., Gersons, B. P., Resick, P. A., . . . Cloitre, M. (2015). Psychotherapies for PTSD: what do they have in common? European journal of psychotraumatology, 6(1), 28186.

Wheatley, J., & Hackmann, A. (2011). Using imagery rescripting to treat major depression: theory and practice. Cognitive and Behavioral Practice, 18(4), 444-453.

World Health Organisation. (2018). International classification of diseases for mortality and morbidity statistics (11th Revision).

Young, J. E., Klosko, J. S., & Weishaar, M. E. (2003). Schema therapy: A practitioner's guide. New York: Guilford Press.

Young, J., Zangwill, W. M., & Behary, W. E. (2002). Combining EMDR and schema-focused therapy: The whole may be greater than the sum of the parts.

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PLoS One. doi: 10.1371/journal.pone.0254778.r003

Decision Letter 1

Andrea Martinuzzi

8 Jun 2021

PONE-D-20-24791R1

Trauma Focused Treatments for Depression. A Systematic Review and Meta-Analysis

PLOS ONE

Dear Dr. Lee,

Besides fixing some typos and grammar problems, both reviewers request a clearer discussion of the limits of the technique and a better clarification of the range of condition considered (marking the difference between PTSD and primary depression). Please address both reviewers comments in your re-revised version.

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Reviewers' comments:

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2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Reviewer #1: I appreciate the responses to the original comments. I still have concerns that the current data does not fully support the claim that TFTs are an effective treatment for depression, given that aside from one study only EMDR is examined. Additionally, the way that depression is being discussed does not fully capture the diagnosis or depression symptoms outside of adversity exposure, which does not occur for all individuals who experience depression. I have expanded on these concerns below.

The types of adversity you are highlighting as leading to depression (e.g., neglect, parental divorce, bullying) are those that are often discussed in research on developmental trauma disorder or complex trauma, proposed diagnoses that are meant to capture exposure to chronic trauma, particularly in childhood (see Pearlman & Courtois, 2005; Van der Kolk et al., 2009). Moreover, causes of depression are not always adversity-based, further highlighting a need to soften these claims. They can be biological, related to lack of achievement/purpose, loss of intimacy, feeling out of control. Individuals with a history of adversity may have more severe symptoms, as you mentioned, and these adversities may not lead to a PTSD diagnosis based on the limitations of the PTSD criteria, but again this is not representative of major depression as a diagnosis - this is representative of the experience of a subset of individuals whose symptoms may actually be captured by a complex trauma diagnosis.

I would like to see some discussion of rumination in the context of your reference to intrusive memories, similar to how you reference avoidance. Rumination is a core feature of depression that often occurs as a strategy to manage intrusive memories and contributes to the frequency/maintenance of intrusive memories. This would support your argument further. Moreover, I would recommend including the review by Payne et al. (2019) to add to the support of the associations between intrusive memories and depression, given that this is more recent than the Wheatley & Hackman (2011) citation and offers some language around why trauma-focused treatments such as EMDR may be beneficial, while also acknowledging limitations.

Though I continue to think the language around TFTs being beneficial for depression should be tempered, I ultimately defer to the editor as I think the findings do make a contribution to the field and highlight the need to further explore TFTs as a treatment for depression. I would, however, like to see the recommendations in the paragraph above addressed, as I think a discussion of rumination in the context of depression/intrusive memories is important (the recent meta-analysis by Mihailova & Jobson, 2018 may be useful) and the updated Payne et al. cite/examination of those findings will add to the paper.

Reviewer #2: Please do a read-through for typos/grammar (e.g. “defied” instead of “defined).

I think it would be helpful to clarify further in the “Selection Criteria” section that participant studies did not require a diagnosis of PTSD (or required NO diagnosis of PTSD?).

I agree with the first reviewer that it still reads to me as a bit misleading in the first and last paragraphs of the discussion to state that TFTs are promising (when really we’re just talking about EMDR). While I understand that the authors set out to examine TFTs (so it makes sense to still label the paper and hypotheses in that way), it seems there should be a middle ground in the discussion that better represents what was found.

It may make sense to mention that if we are examining TFTs for adverse events, that perhaps it no longer makes sense to refer to them as TFT’s (perhaps adversity-orientated treatments?).

One differential between PTSD and depression is “intrusive” thoughts vs “ruminative thoughts”. This made me wonder if depression studies have found that people with depression experience thoughts that are truly “intrusive” in the way defined by PTSD.

**********

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PLoS One. 2021 Jul 22;16(7):e0254778. doi: 10.1371/journal.pone.0254778.r004

Author response to Decision Letter 1

1 Jul 2021

Response to reviewers

Thank you for your comments, we have taken on board your suggestions and believe that this has improved the quality of this manuscript. We have addressed your specific comments below. In addition, we have added the following references:

Birrer, E., & Michael, T. (2011). Rumination in PTSD as well as in traumatized and non-traumatized depressed patients: A cross-sectional clinical study. Behavioural and cognitive psychotherapy, 39(4), 381-397.

Cowdrey, F. A., & Park, R. J. (2012). The role of experiential avoidance, rumination and mindfulness in eating disorders. Eating behaviors, 13(2), 100-105.

Dickson, K. S., Ciesla, J. A., & Reilly, L. C. (2012). Rumination, worry, cognitive avoidance, and behavioral avoidance: Examination of temporal effects. Behavior therapy, 43(3), 629-640.

Mihailova, S., & Jobson, L. (2018). Association between intrusive negative autobiographical memories and depression: A meta‐analytic investigation. Clinical psychology & psychotherapy, 25(4), 509-524.

Newby, J. M., & Moulds, M. L. (2010). Negative intrusive memories in depression: The role of maladaptive appraisals and safety behaviours. Journal of affective disorders, 126(1-2), 147-154.

Payne, A., Kralj, A., Young, J., & Meiser-Stedman, R. (2019). The prevalence of intrusive memories in adult depression: A meta-analysis. Journal of affective disorders, 253, 193-202.

And removed:

Hofmann, A., Hilgers, A., Lehnung, M., Liebermann, P., Ostacoli, L., Schneider, W., & Hase, M. (2014). Eye Movement Desensitization and Reprocessing as an Adjunctive Treatment of Unipolar Depression: A Controlled Study. Journal of EMDR Practice and Research, 8(3), 103-112.

Holmes, E. A., Blackwell, S. E., Heyes, S. B., Renner, F., & Raes, F. (2016). Mental imagery in depression: Phenomenology, potential mechanisms, and treatment implications. Annu Rev Clin Psychol, 12.

Reviewer #1:

I appreciate the responses to the original comments. I still have concerns that the current data does not fully support the claim that TFTs are an effective treatment for depression, given that aside from one study only EMDR is examined. Additionally, the way that depression is being discussed does not fully capture the diagnosis or depression symptoms outside of adversity exposure, which does not occur for all individuals who experience depression. I have expanded on these concerns below.

1. The types of adversity you are highlighting as leading to depression (e.g., neglect, parental divorce, bullying) are those that are often discussed in research on developmental trauma disorder or complex trauma, proposed diagnoses that are meant to capture exposure to chronic trauma, particularly in childhood (see Pearlman & Courtois, 2005; Van der Kolk et al., 2009). Moreover, causes of depression are not always adversity-based, further highlighting a need to soften these claims. They can be biological, related to lack of achievement/purpose, loss of intimacy, feeling out of control. Individuals with a history of adversity may have more severe symptoms, as you mentioned, and these adversities may not lead to a PTSD diagnosis based on the limitations of the PTSD criteria, but again this is not representative of major depression as a diagnosis - this is representative of the experience of a subset of individuals whose symptoms may actually be captured by a complex trauma diagnosis.

Thank you for your comment. In the paper we cite several sources that identify the well-established link between adversities and depression (e. g. Laugharne, Lillee, & Janca, 2010; Nanni, Uher, & Danese, 2012; Risch et al., 2009). While we are not proposing that this is the only factor that impacts on the likelihood of depression or the severity of diagnosis, we are proposing that, similar to biological factors, it is a significant predisposing and maintaining factor for many who have the disorder, and one that is largely neglected in depression interventions. In patients with a trauma-related disorder the characteristics of the traumatic event itself can be different than in patients with depression. In the first case the event has to be related to actual or threat of death, physical or sexual violence, but in the case of depression these events can have a totally different character. In a previous paper treated people with depression without soliciting whether they had a history of adverse events or not (Dominguez, Drummond, Gouldthorp, Janson, & Lee, 2020). The types of traumas that were treated are detailed in the slide below (Dominguez, 2021). In this study we were not treating those patients who would make criteria for complex trauma. These patients would have needed many more sessions to achieve remission of their depression diagnosis. In our revised submission we have elaborated on the prevalence of intrusive memories, and related avoidance and rumination in depressed individuals and the role of these in symptom exacerbation and maintenance as suggested.

2. I would like to see some discussion of rumination in the context of your reference to intrusive memories, similar to how you reference avoidance. Rumination is a core feature of depression that often occurs as a strategy to manage intrusive memories and contributes to the frequency/maintenance of intrusive memories. This would support your argument further. Moreover, I would recommend including the review by Payne et al. (2019) to add to the support of the associations between intrusive memories and depression, given that this is more recent than the Wheatley & Hackman (2011) citation and offers some language around why trauma-focused treatments such as EMDR may be beneficial, while also acknowledging limitations.

Thank you for this comment. We have altered the introduction by updating the information from the Payne et al. (2019) and Mihailova & Jobson (2018) paper and also added information regarding rumination.

3. Though I continue to think the language around TFTs being beneficial for depression should be tempered, I ultimately defer to the editor as I think the findings do make a contribution to the field and highlight the need to further explore TFTs as a treatment for depression. I would, however, like to see the recommendations in the paragraph above addressed, as I think a discussion of rumination in the context of depression/intrusive memories is important (the recent meta-analysis by Mihailova & Jobson, 2018 may be useful) and the updated Payne et al. cite/examination of those findings will add to the paper.

As stated above we have included material on rumination and the references you provided which strengthened the paper. We have further altered the abstract and discussion to be more circumspect around the evidence for TFT in general.

Reviewer #2:

1. Please do a read-through for typos/grammar (e.g. “defied” instead of “defined).

Thank you. This has been addressed.

2. I think it would be helpful to clarify further in the “Selection Criteria” section that participant studies did not require a diagnosis of PTSD (or required NO diagnosis of PTSD?).

We have added the following sentence into the PICO for clarity: “Studies that required participants to have a PTSD diagnosis were excluded from our analysis.”

3. I agree with the first reviewer that it still reads to me as a bit misleading in the first and last paragraphs of the discussion to state that TFTs are promising (when really we’re just talking about EMDR). While I understand that the authors set out to examine TFTs (so it makes sense to still label the paper and hypotheses in that way), it seems there should be a middle ground in the discussion that better represents what was found.

We have altered both the abstract and discussion to ensure this is clearer.

4. It may make sense to mention that if we are examining TFTs for adverse events, that perhaps it no longer makes sense to refer to them as TFT’s (perhaps adversity-orientated treatments?).

This is an interesting idea and our research group discussed this at length. We come to the decision that trauma therapy are common terms used both in the literature and clinical practice and that we can something that neglect, abuse etc are traumatic and that treatments that target anything that is traumatic can be called trauma focused treatment. In thinking through this issue and what is generally meant by the terms we did come across several clinical discussion sites where the concept of possibly two main categories of trauma commonly referred to as Big “T” and little “t.” Big “T” traumas are the events most commonly associated with post-traumatic stress disorder (PTSD) including serious injury, sexual violence, or life-threatening experiences. Little t traumas are any life events experienced by the individual as traumatic but would not fit the PTSD category A diagnostic criteria. We think that the treatment of each should be the same. We thought about writing this up in the discussion but decided it appeared outside the scope of the paper. However we would do this if the editor felt otherwise.

5. One differential between PTSD and depression is “intrusive” thoughts vs “ruminative thoughts”. This made me wonder if depression studies have found that people with depression experience thoughts that are truly “intrusive” in the way defined by PTSD.

We expanded our information on intrusive memories to further specify related avoidance and rumination. We also added a sentence in the discussion to identify that future work in this area is needed.

References

Dominguez, S. (2021). EMDR for depression. Paper presented at the EMDR Europe Research & Practice Conference, Virtual.

Dominguez, S., Drummond, P., Gouldthorp, B., Janson, D., & Lee, C. W. (2020). A randomized controlled trial examining the impact of individual trauma‐focused therapy for individuals receiving group treatment for depression. Psychology and Psychotherapy: Theory, Research and Practice. doi:10.1111/papt.12268

Laugharne, J., Lillee, A., & Janca, A. (2010). Role of psychological trauma in the cause and treatment of anxiety and depressive disorders. Current Opinion in Psychiatry, 23(1), 25-29.

Nanni, V., Uher, R., & Danese, A. (2012). Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry, 169(2), 141-151.

Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., . . . Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. Jama, 301(23), 2462-2471.

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PLoS One. doi: 10.1371/journal.pone.0254778.r005

Decision Letter 2

Andrea Martinuzzi

5 Jul 2021

Trauma Focused Treatments for Depression: A Systematic Review and Meta-Analysis

PONE-D-20-24791R2

Dear Dr. Lee,

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PLoS One. doi: 10.1371/journal.pone.0254778.r006

Acceptance letter

Andrea Martinuzzi

14 Jul 2021

PONE-D-20-24791R2

Trauma-Focused Treatments for Depression. A Systematic Review and Meta-Analysis

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Data Availability Statement

The complete search strategy is detailed in the section with the subheading search strategy in the manuscript and the articles found and analysed are detailed in Table 1.

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PERMALINK

Trauma-focused treatments for depression. A systematic review and meta-analysis

Sarah K Dominguez

Suzy J M A Matthijssen

Christopher William Lee

Roles

Abstract

Background

Methods

Results

Conclusions

Introduction

Method

Search strategy

Selection criteria

Population

Intervention

Comparator

Outcomes

Quality assessment

Meta-analytic procedure

Subgroup and sensitivity analysis

Publication bias

Results

Search results

Fig 1. Flow chart of inclusion of trials for the meta-analysis of studies on trauma-focused treatments and depression.

Characteristics of included studies

Table 1. Description of included studies.

Quality of included trials

Table 2. Quality assessment: Risk of bias.

Effect of TFTs at post-assessment

Table 3. Meta-analysis of studies comparing the effects of trauma-focused treatments on depression.

Fig 2. Standardised effect sizes of trauma-focused treatments for depression compared to control conditions at post-test.

Subgroup analysis at post-assessment

Fig 3. Subgroup analysis: Standardised effect sizes of trauma-focused treatments for depression compared to active and inactive control conditions.

Fig 4. Subgroup analysis: Standardised effect sizes of trauma-focused treatments for depression delivered as an adjunct or standalone therapy, compared to control conditions.

Effects at follow-up

Fig 5. Standardised effect sizes of trauma-focused treatments for depression compared to control conditions at follow-up.

Publication bias

Fig 6. Funnel plot based for main analysis of trauma-focused treatments for depression compared to control conditions at post-test.

Discussion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Andrea Martinuzzi

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Author response to Decision Letter 0

Decision Letter 1

Andrea Martinuzzi

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Author response to Decision Letter 1

Decision Letter 2

Andrea Martinuzzi

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Acceptance letter

Andrea Martinuzzi

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Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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