Treatment effectiveness and efficacy in adults with major depressive disorder and a history of childhood trauma: a systematic review and meta-analysis


Childhood trauma is a common and potent risk factor for developing major depressive disorder in adulthood, associated with earlier onset, more chronic or recurrent symptoms and a greater likelihood of having comorbidities . Some studies indicate that evidence-based pharmacotherapies and psychotherapies for depression in adults may be less effective in patients with a history of childhood trauma than in patients without childhood trauma, but the results are inconsistent. Therefore, we investigated whether people with major depressive disorder, including chronic forms of depression, and with a reported history of childhood trauma, had more severe depressive symptoms before treatment, had worse treatment outcomes unfavorable after active treatments and were less likely to benefit from active treatment. treatments versus a control condition, versus individuals with depression without childhood trauma.


We performed a full meta-analysis (PROSPERO CRD42020220139). The selection of studies combined the search of bibliographic databases (PubMed, PsycINFO and Embase) from November 21, 2013 to March 16, 2020 and full-text randomized clinical trials (RCTs) identified from several sources (from 1966 to 2016 -2019) to identify articles in English. RCTs and open-label trials comparing the effectiveness or efficacy of an evidence-based combination pharmacotherapy, psychotherapy, or intervention for adult patients with depressive disorders and the presence or absence of childhood trauma were included. Two independent researchers extracted the characteristics of the study. Group data for effect size calculations were requested from the study authors. The primary outcome was the change in depression severity between the start and end of the acute treatment phase, expressed as standardized effect size (Hedges g). Meta-analyses were performed using random-effects models.


Of 10,505 publications, 54 trials met the inclusion criteria, of which 29 (20 RCTs and nine open-label trials) provided data on up to 6830 participants (age range 18-85 years, men and women and specific ethnic data not available). More than half (4268 [62%] of 6830) patients with major depressive disorder reported a history of childhood trauma. Despite more severe depression at baseline (g=0 202, 95% CI 0 145 to 0 258, I2= 0%), patients with childhood trauma received active treatment in the same way as patients without a history of childhood trauma (difference in treatment effect between groups g = 0 016, -0 094 to 0 125, I2=44 3%), with no significant difference in the effects of active treatment (versus control condition) between individuals with and without childhood trauma (childhood trauma g=0 605, 0 294 to 0 916, I2=58 0%; no childhood trauma g=0 178, –0 195 to 0 552, I2=67.5%; difference between groups p=0 051), and similar dropout rates (relative risk 1 063, 0 945 to 1 195, I2=0%). Results did not differ significantly by type of childhood trauma, study design, diagnosis of depression, method of childhood trauma assessment, study quality, year or type or duration of treatment, but differed by country (North American studies showed larger treatment effects for patients with childhood trauma; corrected false discovery rate p=0 0080 ). Most studies were at moderate to high risk of bias (21 [72%] of 29), but sensitivity analysis in low-bias studies yielded results similar to those obtained when all studies were included.


Unlike previous studies, we found evidence that the symptoms of patients with major depressive disorder and childhood trauma improved significantly after pharmacological and psychotherapeutic treatments, despite the higher severity of their depressive symptoms. . Evidence-based psychotherapy and pharmacotherapy should be offered to patients with major depressive disorder, regardless of their childhood traumatic condition.



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