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European Journal of Psychotraumatology logoLink to European Journal of Psychotraumatology
. 2023 Oct 5;14(2):2258313. doi: 10.1080/20008066.2023.2258313

Changes in comorbid depression following intensive trauma-focused treatment for PTSD and complex PTSD

Cambios en la depresion comorbida despues de un tratamiento intensivo focalizado en trauma para TEPT y TEPT complejo

针对 PTSD 和复杂性 PTSD 进行强化创伤聚焦治疗后与抑郁障碍共病的变化

Paul Paridaen a,b, Eline M Voorendonk a,c, Georgy Gomon d, Elisabeth A Hoogendoorn e, Agnes van Minnen a,c, Ad de Jongh a,f,g,h,CONTACT
PMCID: PMC10557564  PMID: 37796651

ABSTRACT

Background:

The extent to which intensive trauma-focused treatment for individuals with post-traumatic stress disorder (PTSD) is also effective in treating comorbid major depressive disorder (MDD) remains unclear.

Objective:

The purpose of the present study was to test the hypothesis that brief intensive trauma-focused therapy for PTSD is associated with significant reductions in depressive symptoms and loss of diagnostic status of MDD.

Methods:

A total of 334 adult patients with PTSD (189 patients who were also diagnosed with MDD) underwent a brief intensive trauma-focused treatment programme consisting of EMDR therapy, prolonged exposure, physical activity, and psychoeducation. At pre-treatment, post-treatment and 6-month follow-up, severity and diagnostic status of PTSD and MDD were assessed. A linear mixed model was used to analyze changes in the severity of PTSD and depressive symptoms, whereas a generalized linear mixed model was used to determine changes in the MDD diagnostic status.

Results:

Treatment resulted in a significant and strong decrease of PTSD and MDD symptoms at post-treatment (d = 2.34 and 1.22, respectively), and at 6-month follow-up (d = 1.67 and 0.73, respectively). The proportion of patients fulfilling the diagnostic status of MDD changed from 57% at pre-treatment to 33% at the 6-month follow-up. Although the initial response to treatment did not differ between patients with and without comorbid MDD, for both groups a significant relapse in depressive symptoms was found after six months, which could be explained almost entirely by the presence of CPTSD at baseline.

Conclusions:

The results support the notion that brief, intensive trauma-focused treatment is highly effective for individuals with PTSD and comorbid MDD. Because patients with CPTSD are vulnerable to relapse in depressive symptoms, this target group may require additional treatment.

KEYWORDS: Complex post-traumatic stress disorder (CPTSD), major depressive disorder (MDD), intensive trauma-focused treatment, EMDR therapy, prolonged exposure therapy, linear mixed model

HIGHLIGHTS

  • Intensive trauma-focused treatment (ITFT) of PTSD proved to be associated with a significant decrease in comorbid MDD.

  • Comorbid MDD did not moderate the effect of ITFT for PTSD.

  • Presence of Complex PTSD was predictive of relapse of MDD symptoms 6 months later.

1. Introduction

Research suggests that when post-traumatic stress disorder (PTSD) co-occurs with depression, patients have an elevated risk of psychopathological symptoms and disorders, along with a poorer prognosis in terms of general health, as compared to patients with PTSD alone. (Kline et al., 2021; Post et al., 2011).

The co-occurrence of PTSD and major depressive disorder (MDD) is high, with an average of 52% of individuals with PTSD meeting the DSM-5 diagnostic criteria for MDD (American Psychiatric Association, 2013; Rytwinski et al., 2013). For patients with a history of childhood abuse, the likelihood that PTSD and MDD co-occur is substantially higher than for those without such a history (Kilpatrick et al., 2003). The co-occurrence of PTSD and MDD can be partly explained by the fairly large overlap between the constructs and diagnostic criteria of PTSD and MDD (Burton et al., 2021; Post et al., 2011). This overlap has grown with the introduction of the PTSD symptom cluster ‘negative alterations in cognition and mood’ within the DSM-5 (Hurlocker et al., 2018).

Within the other commonly used classification system for mental health, the 11th edition of the International Classification of Diseases (ICD-11; World Health Organization, 2018), symptoms concerning mood in combination with PTSD are part of a separate classification, termed Complex PTSD (CPTSD). This severe form of PTSD is defined as the presence of both PTSD and affective dysregulation, disturbances in relationships, and negative self-concept, the so-called disturbances in self-organization (DSO) symptoms (Maercker et al., 2022).

While international guidelines do not specifically mention PTSD with comorbid MDD (e.g. Guideline Development Panel for the Treatment of PTSD in Adults, American Psychological Association, 2019), comorbid MDD in patients with PTSD is associated with higher dropout rates (Levi et al., 2019; Markowitz et al., 2015) and is sometimes considered a contraindication for trauma-focused treatment in clinical practice (Van Minnen et al., 2012). Indeed, evidence suggests that comorbid MDD has a detrimental effect on the effectiveness of treatment for PTSD (Dewar et al., 2020; Kline et al., 2021), and that residual symptoms of depression after effective treatment for PTSD are common (Larsen et al., 2019). In contrast, a meta-analysis of 116 treatment comparisons from 93 clinical trials found that effective treatments for PTSD were also effective in reducing comorbid MDD (Ronconi et al., 2015). The main criticisms of the studies included in this meta-analysis were the lack of follow-up measurements and the great diversity between studies. For example, the studies differed in the methods used to measure MDD, type of treatment, and inclusion of patients with CPTSD (Karatzias & Cloitre, 2019). In the past, experts have argued that its presence would hinder trauma-focused treatment (De Jongh et al., 2016).

As for the form of treatment of PTSD, much progress has been made in recent years in the development of intensive trauma-focused treatment programmes for PTSD. They have been found to be safe, feasible, and well-tolerated treatment alternatives with very low levels of dropout and symptom exacerbation (Sciarrino et al., 2020). This treatment format has been proven beneficial for individuals exposed to childhood sexual abuse (Wagenmans et al., 2018), and those suffering from CPTSD (Voorendonk et al., 2020). To date, it is unclear whether brief intensive trauma-focused treatment of PTSD is also effective in treating comorbid MDD.

Given the aforementioned research findings, the purpose of the present study was to determine the changes in MDD (symptoms and DSM-5 diagnostic status) associated with the application of trauma-focused treatment for PTSD. We hypothesized that MDD symptoms would significantly decline after treatment, that a significant proportion of PTSD patients who met the diagnostic criteria for MDD at pre-treatment would lose their diagnostic status at post-treatment, and that this would still be the case at 6-month follow up. Furthermore, we examined whether the presence of comorbid MDD moderates the change in PTSD symptoms following brief intensive trauma-focused treatment. More specifically, we hypothesized that patients who fulfilled the diagnostic criteria for MDD before treatment and those who did not fulfill the diagnostic criteria for MDD before treatment would both show a significant decrease in the severity of PTSD symptoms. Finally, since there is evidence to suggest that CPTSD may influence treatment outcomes in patients with PTSD and MDD (Cloitre et al., 2013; Post et al., 2021), we also investigated the influence of CPTSD at baseline on treatment outcomes regarding symptom decline and diagnostic status, both for PTSD and MDD.

2. Method

2.1. Participants

The participants were adult individuals diagnosed with PTSD who were enrolled in an intensive trauma-focused programme at a treatment center for PTSD (PSYTREC; the Netherlands) between August and November 2019. All participants were referred for treatment by a general practitioner or an institute for mental health. To be eligible for the treatment programme patients had to (1) meet the DSM-5 criteria for PTSD classification, (2) have sufficient proficiency in the Dutch language to be able to undergo treatment (3), and no history of suicide attempts in the three months prior to the entry of the treatment programme. In total, 398 patients were included in this study. Of these, 350 patients provided informed consent, of which 16 did not complete the treatment, yielding a total of 334 patients (see Figure 1).

Figure 1.

Study flowchart showing that of 350 included patients analyses were done on 334 patients because 16 dropped out. The numbers and percentages of patients for whom data could be collected with the four measuring instruments used are shown at the bottom of the chart in three in three blocks regarding pre-treatment, post-treatment and follow-up.

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Study flowchart with the percentage of available data per measurement in parentheses.

Note. CAPS-5 = Clinician-Administered PTSD Scale; QIDS-SR = Quick Inventory of Depressive Symptomatology, 16 item Self Report; MINI = Mini Neuropsychiatric Interview; ITQ = International Trauma Questionnaire.

2.2. Procedure

After referral, patients were invited for two intake sessions at the treatment centre to assess whether they were eligible to participate in the treatment programme and to make an individual treatment plan. At the first intake session the pre-treatment measurements of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), Quick Inventory of Depressive Symptomatology (QIDS-SR), International Trauma Questionnaire (ITQ) and The Mini-International Neuropsychiatric Interview (MINI) were performed. On average, patients started with treatment 28 days after the first intake session.

All patients attended the eight-day inpatient treatment which consisted of two four-day periods interrupted by a period of three days at home without any treatment. Eight days after the last treatment day, the patients returned to the treatment center for an evaluation interview about the treatment and to assess post-treatment measurements of the CAPS-5, QIDS-SR, and MINI. Six months after the post-treatment evaluation, follow-up measurements of the CAPS-5 and MINI were assessed via telephone sessions, and the QIDS-SR was assessed online. Ethical exemption was assigned by the Medical Ethical Review Committee of VU University Medical (registered with the US Office for Human Research Protection (OHRP) as IRB00002991, FWA number FWA00017598).

2.3. Treatment

Each treatment day had the same structure in that the patients received two 90-minute individual trauma-focused therapy sessions by alternating therapists (i.e. ‘therapist rotation,’ Van Minnen et al., 2018), consisting of prolonged exposure therapy in the morning and eye movement desensitization and reprocessing (EMDR) therapy in the afternoon, interspersed with professionally guided physical activities (four times a day) and psychoeducation about PTSD. For more information about the treatment programme see Woudenberg et al. (2018).

2.4. Measures

The Clinician-Administered PTSD Scale (CAPS-5) serves as the ‘gold standard’ in diagnosing PTSD and measuring its symptom severity (Weathers et al., 2018; Dutch version: Boeschoten et al., 2018). The CAPS is a clinical structured interview containing 20 items which assess the DSM-5 PTSD symptoms. For each item, the clinician rated it on a scale of 0 to 4. A symptom was scored as present when the item score was ≥ 2. The overall PTSD symptom severity was measured by computing a sum score based on these 20 items. The total score ranged from 0 to 80.

To establish an MDD diagnosis and other comorbid disorders the Dutch version of the Mini International Neuropsychiatric Interview PLUS (MINI-PLUS; Overbeek et al., 1999) was used. The MINI is a structured, diagnostic interview used to establish the DSM- diagnoses. At pre-treatment the full MINI was administered to assess MDD and other comorbid psychological disorders. At post-treatment and follow-up only the section concerning depressive disorders was administered (Lecrubier et al., 1997; Sheehan et al., 1998).

The Quick Inventory of Depressive Symptomatology (QIDS-SR16; Rush et al., 2003) was used to assess the symptomatology of MDD. The QIDS-SR16 is a self-report questionnaire. The questionnaire consists of 16 items that cover the nine symptom domains used to diagnose a major depressive episode in the DSM-IV-TR (American Psychiatric Association, 2000). The QIDS-SR16 is an abbreviated version of the Inventory of Depressive Symptomatology (IDS; Rush et al., 2000). In comparison with the IDS, the QIDS-SR16 does not include items concerning atypical and melancholic specifiers and associated symptoms. The response for each item has a 0 to 3 range. When a symptom domain is addressed in more than one item, the highest scored item is used to calculate the total score. One score was used for each symptom domain. Thus, the total score ranges from 0 to 27. The total score provides an estimate of depression severity in the following categories: none (0–5), mild (6–10), moderate (11–15), severe (16–20), or very severe (≥21) (Rush et al., 2003).

The Dutch version of the International Trauma Questionnaire (ITQ; Eidhof et al., 2018) was used to determine whether the patients met the diagnosis of CPTSD according to the criteria of the ICD-11. The ITQ is considered to be a valid instrument for assessing these criteria (Cloitre et al., 2018). To qualify for a CPTSD diagnosis, all six symptom clusters must present and cause impairment in at least one area of daily life (i.e. work, school, and social life). This concerns three PTSD symptom clusters (re-experiencing, avoidance, and sense of threat) and three DSO symptom clusters (affective dysregulation, disturbances in relationships, and negative self-concept). A symptom cluster (each consisting of two symptoms) is considered present when for both symptoms the score is ≥ 2 on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). Based on the ITQ, the patients were divided into three groups; the ITQ-CPTSD group (all six symptom clusters present), the ITQ-PTSD group (not all six but all three PTSD symptom clusters present) and the ITQ-DSO group (not all six but all three DSO symptom clusters present).

2.5. Statistical analyses

To assess MDD and PTSD severity over time, linear mixed models (LMMs) with random intercepts and random slopes on the intent-to-treat sample were used to fit the QIDS and CAPS-5 scores, respectively. In addition, a logistic generalized linear mixed model (GLMM) with random intercepts was fitted to model the binary outcome of MDD diagnosis over time, as measured by the MINI. Initially, the models were fitted with only time as covariate (and MDD vs. no MDD for the model having the CAPS-5 score as outcome variable). To account for possible confounding, all models were subsequently extended by including the covariates sex, ITQ classification at intake, and their two-way interactions with time. Overall, the LMMs and GLMM fitted the data well, as no assumption violations were observed. No techniques to deal with missing data were used, as mixed models are valid in the case of data missing at random. Using the definitions of reliable change index (RCI) and clinical significance (CS), patients were classified as Recovered, Improved, Unchanged or Deteriorated (Wise, 2004). Considerable missing data may affect the interpretation of these results during follow-up (for detailed information about the statistical analyses, see Supplement A).

3. Results

3.1. Descriptives

In Table 1 sample characteristics are shown for people with (n = 189) and without (n = 143) comorbid MDD. In the comorbid MDD group a statistically higher depression (t[289.16] = 8.51, p < .001) and PTSD severity (t[312.58] = 4.35, p < .001), as well as a higher incidence of anxiety disorders (χ2[1] = 8.90, p = .003) were observed. The results also showed a different distribution of ITQ classification (χ2[2] = 23.79, p < .001), with a higher prevalence of CPTSD in the group with comorbid MDD (67% in the group with MDD vs. 48% in the group without MDD).

Table 1.

. Sample characteristics at intake for the groups with and without comorbid MDD.

Variable Total N = 334a Comorbid MDD n1 = 189 No comorbid MDD n2 = 143 Chi-squared test: χ2 p-value
Sex
 Male 120 (36%) 69 (37%) 51 (36%) 0.002 .996
 Female 214 (64%) 120 (63%) 92 (64%) n.a. n.a.
ITQ classificationb
 ITQ-PTSD 88 (26%) 30 (16%) 58 (40%) 23.785 <.001
 ITQ-CPTSD 197 (59%) 127 (67%) 68 (48%) n.a. n.a.
 ITQ-DSO 29 (9%) 17 (9%) 12 (8%) n.a. n.a.
Comorbidity          
 Anxiety disorders 174 (52%) 113 (60%) 61 (43%) 8.904 .003
 Psychotic disorders 38 (11%) 23 (12%) 15 (10%) 0.091 .763
 Substance abuse 9 (3%) 5 (3%) 4 (3%) n.a. n.a.
Type of trauma
Sexual trauma 301 (90%) 171 (90%) 128 (90%) 0.011 .916
 trauma ≤ age of 12 127 (42%) 73 (43%) 52 (41%)    
 trauma > age of 12 174 (58%) 98 (57%) 76 (59%)    
Physical trauma 318 (95%) 183 (97%) 134 (94%) 1.184 .277
Natural disasters & accidents
 273 (82%)
 158 (84%)
 113 (79%)
 0.852
 .356
 
  
  
  
 Welch’s t-test: t-value
 p-value
Age, M (SD) 40.55 (12.79) 40.25 (12.76) 40.81 (12.84) −0.398 .691
CAPS score, M (SD) 42.79 (7.74) 44.35 (7.71) 40.72 (7.37) 4.357 <.001
QIDS scorec, M (SD) 15.43 (4.55) 17.21 (4.10) 13.19 (4.11) 8.506 <.001
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a

Total N = 334 deviates from the sum of n1 and n2, because there are two missing values for the assessment of the binary MDD diagnosis variable.

b

The total sum of subjects with an ITQ classification equals only 314, as there are 20 missing values (of which 15 in the comorbid MDD group and 5 in the group without comorbid MDD).

c

The total sample size was N = 308 due to 26 missing values. Hereby 7 are missing in the group without comorbid MDD, and 19 were missing in the group with comorbid MDD.

3.2. Change in severity of depression

A linear mixed model revealed a significant overall change in QIDS scores over time, F[2, 491] = 175.63, p < .001. Post-hoc analyses showed a significant decrease from pre-treatment to post-treatment (d = 1.22, t[491] = −18.74, p < .001) and from pre-treatment to follow-up (d = 0.73, t[491] = −10.54, p < .001). The increase from post-treatment to follow-up was also significant (d = 0.36, F[1, 491] = 44.05, p < .001).

A more elaborate model including the covariates of sex and ITQ classification at intake (see supplement Table 1) supported the significant time effects indicated by the simple model. Sex did not significantly predict the QIDS scores over time (χ2[3] = 2.36, p = .501). ITQ classification at intake did, in that, compared to the ITQ-PTSD group, the ITQ-CPTSD group had a 4.68 points higher QIDS score at pre-treatment (d = 1.11, t[306] = 8.66, p < .001). The group that, based on the ITQ, only qualified for the DSO symptom cluster (ITQ-DSO group) had a 2.16 points higher QIDS score at pre-treatment (d = 0.52, t[306] = 2.44, p = .031) than the ITQ-PTSD group. It is important to note that the intercept and differences at pre-treatment influenced the scores at other time points. In addition, a significant interaction between time and ITQ classification was found (F[6, 479] = 2.25, p = .038). Specifically, QIDS scores in the ITQ-CPTSD group dropped by 2.08 points more from pre-treatment to post-treatment compared to the ITQ-PTSD group. Furthermore, relapse from post-treatment to the 6-months follow-up was significant for the ITQ-CPTSD group (d = 0.43, F[1,479] = 33.95, p < .001) and the ITQ-DSO group (d = 0.43, F[1,479] = 5.78, p = .017), but not for the ITQ-PTSD group (d = 0.20, F[1, 479] = 0.94, p = .334; Figure 2). An exploratory analysis indicated that none of the DSO subscales were highly correlated with the relapse observed, indicating that the DSO symptom cluster as a whole predicted relapse.

Figure 2.

A graph with 4 lines showing the course of the QIDS-scores. On average and for the three ITQ groups (ITQ-CPTSD, ITQ-DSO, ITQ-PTSD). It is striking that all lines show a relapse from post-treatment to follow-up, with the exception of the ITQ-PTSD group.

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Depression severity was measured using the QIDS-SR over time for each ITQ classification group (as measured at intake), as well as the overall time trajectory.

Note. QIDS-SR = Quick Inventory of Depressive Symptomatology Self Report; ITQ = International Trauma Questionnaire; CPTSD = Complex PTSD.

Based on the reliable change index (RCI) and clinical significance (CS) 81 patients (43%) showed a clinically reliable improvement from pre-treatment to post-treatment, whereas three patients (2%) showed a clinically reliable deterioration (supplementary Table 2). From pre-treatment to follow-up these numbers were 40 (21%) and three (2%) patients, respectively.

3.3. Change in MDD diagnostic status

A generalized linear mixed model indicated a significant change in the proportion of MDD diagnostic status across different time points (χ2­[2] = 83.51, p < .001). Post-hoc analyses revealed a significant decrease in MDD diagnostic status proportions from 57% at pre-treatment to 21% at post-treatment (z = −9.00, p < .001), and 33% at follow-up (z = −5.71, p < .001; see Figure 3). A Wald test indicated a significant increase from post-treatment to follow-up (χ2[1] = 12.11, p < .001).

Figure 3.

A bar chart showing the percentage of patients who do or do not meet the diagnosis of MDD. The percentage meeting the diagnosis is 57% at pre-treatment, 21% at post-treatment and 33% at follow-up.

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Percentage of patients with an MDD diagnosis, according to the MINI, over time.

Note: MINI = Mini-International Neuropsychiatric Interview.

An extended model controlling for sex and ITQ classification at intake (see supplementary Table 3) supported the observed significant overall time-effect. Compared with the linear mixed model, the interaction of ITQ classification with time was not significant (χ2[4] = 7.27, p = .122). Nevertheless, we ran a post-hoc analysis with this interaction from an exploratory perspective and compared the results with those obtained by the linear mixed model. For the ITQ-PTSD group a significant decrease from pre-treatment to post-treatment (z = −3.29, p = .006) was found with no change from post-treatment to follow-up (χ2[1] = 1.07, p = .301). The ITQ-CPTSD group also showed a significant decrease from pre-treatment to post-treatment (χ2[1] = 66.05, p < .001), but also a relapse from post-treatment to follow-up (χ2[1] = 13.84, p < .001) (see Supplementary Figure 1).

Furthermore, a significantly higher proportion of MDD diagnoses at pre-treatment was observed in both the ITQ-CPTSD (z = 4.67, p < .001) and ITQ-DSO group (z = 2.38, p = .042). Although no pre-treatment difference was observed between the sexes in the proportion of MDD diagnoses (z = −1.12, p = .263), a significant interaction between sex and time was found using the Wald test (χ2[2] = 6.51, p = .038).

3.4. Change in PTSD severity for individuals with and without comorbid MDD

A linear mixed model indicated a significant overall decrease in CAPS-5 scores over time (F[2, 596] = 285.43, p < .001, Table 2). In addition, the MDD group showed significantly higher CAPS-5 scores than the non-MDD group at pre-treatment (d = 0.48, t[330] = 4.33, p < .001); this difference remained present at post-treatment and follow-up. Given this constant difference, the time trajectories, as shown in Figure 4, for CAPS-5 scores did not differ between the groups, F[2, 596] = 0.45, p = .637.

Table 2.

Model summary of the linear mixed model for predicting PTSD severity in people with and without comorbid MDD (N = 332a).

Parameter Value Std. Error p-value
Intercept 40.72 0.63 <.001
Time (versus pre-treatment)
Post-treatment −27.08 1.13 <.001
Follow-up −22.41 1.29 <.001
MDD-diagnosis (versus no MDD) 3.63 0.84 <.001
Interaction Time * MDD diagnosis
Post-treatment * MDD 1.25 1.50 .405
Follow-up * MDD 1.56 1.72 .365
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a

Total sample size of people with (n1 = 189) and without MDD (n2 = 143); 2 missing values with no pre-treatment MDD diagnosis.

Figure 4.

A two-line graph showing the progression of CAPS-5 scores over time. The lines run almost parallel, with the line for patients with comorbid MDD running 4 to 6 points higher than the line for PTSD without comorbid MDD. Visible is a strong decrease of the CAPS-5 score from pre-treatment to post-treatment and a slight increase from post-treatment to follow-up.

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Estimated trajectories of CAPS-5 scores over the three time points for the group with MDD versus those without comorbid MDD.

Note: CAPS-5 = Clinician-administered PTSD Scale.

A more extensive model, including the covariates of sex and ITQ classification at intake, was fitted (see Supplementary Table 4). In this more elaborate model, the time effects, as well as the consistently higher CAPS-5 scores at all time points in the MDD group, were unchanged. However, the presence of CPTSD (ITQ-CPTSD group) yielded higher CAPS-5 scores at all time points than the ITQ-PTSD group (t[307] = 4.55, p < .001), whereas the ITQ-DSO group did not differ from the ITQ-PTSD group in terms of CAPS-5 scores (t[307] = −0.43, p = .691). Note that although the ITQ-CPTSD group had higher overall CAPS-5 scores, given this constant, the time trajectories did not differ between the groups (χ2 [4] = 4.91, p = .297).

From pre-treatment to post-treatment, 304 patients (91%) showed clinically reliable improvement in PTSD symptoms, whereas one patient (<1%) showed clinically reliable deterioration. From pre-treatment to follow-up, these numbers were 225 (67%) and 5 (1%), respectively (see Supplementary Table 5).

4. Discussion

The results of the present study show a significant decrease in depressive symptoms and loss of MDD diagnostic status associated with eight days of intensive trauma-focused treatment, independent of sex. From pre-treatment to post-treatment, almost half of the patients showed improvement or even full recovery. The percentage of patients with diagnostic status of MDD changed from 57% at pre-treatment to 33% at the 6-month follow-up. These results support our hypothesis that a significant proportion of PTSD patients who met the diagnostic criteria for MDD at pre-treatment lost their diagnostic status at post-treatment and at 6-month follow up. Furthermore, the observed decrease is in line with earlier research showing that trauma-focused interventions targeting memories of A-criterion events are capable of significantly reducing MDD symptoms (e.g. Ronconi et al., 2015; Van Minnen et al., 2015). The present study is one of the first to show that these changes can be maintained for at least six months after treatment.

The decrease in PTSD symptoms did not differ between patients with and without comorbid MDD (d = 2.34 and 1.67 at post-treatment and at 6-months follow-up, respectively), nor was there a significant difference in the reduction of PTSD symptoms between men and women. This is in line with the notion that PTSD is highly comorbid with MDD, and supports our hypothesis that the presence of MDD does not hinder the efficacy of trauma-focused treatment. How best to explain this overlap in symptomatology has been extensively studied, but this has not yet led to an unambiguous conclusion (Burton et al., 2021). After 6 months a significant relapse in the depressive symptoms occurred, which was almost completely explained by the presence of CPTSD based on the ITQ scores at baseline. The finding that patients with PTSD with and without comorbid MDD showed similar decreases in PTSD symptoms associated with intensive trauma-focused treatment, both at post-treatment and at 6-month follow up, is in accordance with previous studies (Assmann et al., 2021). It should be noted that these results have never been reported in response to an intensive treatment programme lasting no longer than two weeks.

However, based on the scores on the ITQ the results showed a clear difference between patients with either PTSD or CPTSD. Although the treatment response between patients with and without comorbid CPTSD was not significantly different, the relapse in MDD symptoms proved to be explained almost entirely by the presence of CPTSD at baseline. The fact that such relapse was hardly present in the ITQ-PTSD group may indicate that the presence of a DSO symptom cluster, which distinguishes CPTSD from PTSD, and pertains to disturbances in relationships and negative self-concept, may be responsible for this relapse. This was confirmed by our exploratory analysis, which showed that the DSO symptom cluster as a whole, rather than the DSO subscales, predicted relapse. Although more research is needed, these findings suggest that at least some patients, after treatment for (C)PTSD, need additional interventions to prevent a relapse of depressive symptoms.

Among the strengths of the present study are the six-month follow-up measurement of MDD in terms of both symptoms and diagnostic status. Furthermore, this is the first study to investigate the effects of trauma-focused treatment on depression within the context of an intensive PTSD treatment programme. In addition, since there is evidence that physical activity can be beneficial for depressive symptoms in patients with PTSD (e.g. Davis et al., 2021), these activities might have been (partly) responsible for the effects found in this study. Nevertheless, a recent randomized controlled trial showed that the decrease in depressive symptoms, directly following intensive trauma-focused treatment, was not differentially influenced by additional physical activity in comparison to adding non-physical activity control tasks (Voorendonk et al., 2023).

However, this study has several limitations. First, because no control group was used, we cannot claim an effect due to treatment, only of a change over time. On the other hand, the changes from pre-treatment to post-treatment occurred within a short time (M = 80 days, SD = 20 days), which is difficult to explain solely by phenomena such as natural recovery or the passing of time. This is certainly true for tertiary care patients, such as those referred to our treatment facility, who without intervention, typically show limited natural changes in MDD and PTSD over significantly longer time periods (Sadock et al., 2007). Thus, although future studies using a wait-list control group or an active control group are needed to corroborate the presented results, the changes in MDD and PTSD severity found in the present study are most likely the result of intensive trauma-focused treatments. Second, we treated time as a factor in this study, although the time between measurements was not equal for all patients, with 50 outliers. As a check, we performed all analyses without outliers and found that they did not influence our results. The overall classification of patients using RCI and CS should be treated with care, especially at follow-up where the percentage of missing data is considerable (see Figure 1). Finally, it should be noted that whereas the current results do not apply to a certain group of highly unstable patients – as the study excluded patients who had attempted suicide within three months prior to pre-treatment – the results do generalize to severe depression (according to the standards of Rush et al., 2003, the average depression score of the individuals with comorbid MDD on the QIDS, M = 17.21, SD = 4.10, needs to be considered ‘severe’).

The present results give rise to several practical implications. First, these findings imply that MDD is amenable to change when only memories of A-criterion events are targeted. In addition, given that comorbid MDD does not affect the decrease in PTSD symptoms over time, the results suggest that we can treat patients with PTSD and comorbid MDD in the same way as in patients without this comorbidity. Our results support the notion that symptoms of comorbid MDD in existing forms of severe PTSD do not have to be reduced before starting PTSD treatment, as it can be expected that both PTSD and depressive symptoms diminish in association with the extent to which the memories driving these trauma-related complaints are successfully processed. While it is still of vital importance to assess the best course of treatment for each patient at an individual level, the current study supports the notion that intensive trauma-focused treatment should not be withheld from patients with PTSD and comorbid MDD. Moreover, therapists should not be reluctant to treat patients with PTSD and comorbid MDD because of the risk of dropout.

In conclusion, the results of the present study support the notion that brief, intensive trauma-focused treatment is highly effective for individuals with PTSD and comorbid MDD but that those with probable CPTSD are vulnerable to relapse in depressive symptoms. More research into the long-term effects of trauma-focused treatment in patients with comorbid MDD is needed, with specific attention to the possible mediating role of the presence of CPTSD.

Supplementary Material

Supplemental Material
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Supplemental Material
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Funding Statement

No funding was received for this study.

Data availability

Data are available on request owing to privacy/ethical restrictions. The data that support the findings of this study are available upon request from the corresponding author, AdJ. The data are not publicly available, because they contain information that can compromise the privacy of research participants. Furthermore, the participants were not asked to provide consent to save their data in a public data repository.

Disclosure statement

Agnes van Minnen receives income from published book chapters on PTSD and the training of postdoctoral professionals in prolonged exposure. Ad de Jongh receives income from published books on EMDR therapy and the training of postdoctoral professionals in this method. The other authors have no competing interests to declare.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental Material
Click here for additional data file. (64.4KB, docx)
Supplemental Material
Click here for additional data file. (9.4MB, tiff)

Data Availability Statement

Data are available on request owing to privacy/ethical restrictions. The data that support the findings of this study are available upon request from the corresponding author, AdJ. The data are not publicly available, because they contain information that can compromise the privacy of research participants. Furthermore, the participants were not asked to provide consent to save their data in a public data repository.

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