Treatment efficacy and effectiveness in adults with major depressive disorder and childhood trauma history: 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 comorbidities. Some studies suggest that evidence-based pharmacotherapies and psychotherapies for adult depression may be less effective in patients with a history of childhood trauma than in those without childhood trauma, but the results are conflicting. Therefore, we examined whether individuals with major depressive disorder, including chronic forms of depression, and a reported history of childhood trauma, had more severe depressive symptoms before treatment, had less favorable treatment outcomes after active treatments, and were less likely to benefit from active treatments relative to a control disorder im Compared to people with depression without childhood trauma.


We performed a comprehensive meta-analysis (PROSPERO CRD42020220139). Study selection combined searches of bibliographic databases (PubMed, PsycINFO, and Embase) from November 21, 2013 to March 16, 2020 and full-text randomized clinical trials (RCTs) identified from multiple sources (1966 to 2016–19). Identify articles in English. RCTs and open-label studies comparing the efficacy or effectiveness of an evidence-based pharmacotherapy, psychotherapy, or combination intervention in adult patients with major depressive disorders and the presence or absence of childhood trauma were included. Two independent investigators extracted study characteristics. Group data for effect size calculations were requested by the study authors. The primary endpoint was change in depression severity from baseline to the end of the acute treatment period, expressed as a standardized effect size (Hedges’ g). Meta-analyses were performed using random effects models.

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Out of 10,505 publications, 54 studies met the inclusion criteria, of which 29 (20 RCTs and nine open-label studies) contributed data from a maximum of 6830 participants (age range 18-85 years, males and females, and specific ethnic data not available). More than half (4268 [62%] of 6830) of patients with major depressive disorders reported a history of childhood trauma. Despite having more severe depression at baseline (g=0.202, 95% CI 0.145 to 0.258, I2= 0%), patients with childhood trauma benefited from active treatment similarly to patients without a history of childhood trauma (treatment effect difference between groups g = 0.016, −0.094 to 0.125, I2=44.3%), with no significant difference in the effects of active treatment (vs control condition) between people 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 (hazard ratio 1.063, 0.945 to 1.195, I2=0%). Results did not differ significantly by type of childhood trauma, study design, depression diagnosis, childhood trauma assessment method, study quality, year, or treatment type or duration, but they did differ by country (North American studies showed greater treatment effects for patients with childhood trauma; false detection rate corrected p=0 0080 ). Most studies had a medium to high risk of bias (21st [72%] of 29), but the sensitivity analysis in low-bias studies yielded similar results as when all studies were included.

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In contrast to previous studies, we found evidence that the symptoms of patients with major depressive disorders and childhood trauma improve significantly after pharmacological and psychotherapeutic treatments, despite their higher severity of depressive symptoms. Evidence-based psychotherapy and pharmacotherapy should be offered to patients with major depressive disorders regardless of childhood trauma status.

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