In this Featured Perspectives in Major Depressive Disorder article, new insights on the effect of childhood trauma on treatment response are provided, touching on data from a recent metaanalysis.

• Despite findings in the literature indicating that evidence-based therapies for major depressive disorder (MDD) might be less efficacious in patients with a history of childhood trauma, the present meta-analysis shows that patients with and without childhood trauma experience similar improvements in depressive symptoms during acute treatment (ie, evidence-based psychotherapy and pharmacotherapy).
• Patients with MDD and a history of childhood trauma have more severe symptoms at baseline than those with MDD and control conditions; however, these individuals experience a similar degree of symptom improvement with acute treatment.
• Patients with MDD and a history of childhood trauma should be offered evidence-based therapies and personalized care to address their more severe baseline MDD symptoms and the potential long-term negative effects of childhood trauma on their MDD.

Childhood trauma is a risk factor for MDD in adulthood and is associated with more severe symptoms, residual symptoms after treatment, and more frequent relapses compared with individuals with MDD who did not experience trauma. Data on treatment response in patients who experienced childhood trauma are inconclusive. Some studies suggest that individuals with a history of trauma may be less responsive to evidence-based therapies, which raises questions about the value of treatment in this setting. Data on the relative contributions of different types of trauma to outcomes are also lacking but might assist in personalizing care.

A meta-analysis of 29 clinical trials enrolling 6830 adults with MDD compared change from baseline in depressive symptoms during the acute phase of treatment in subpopulations with (n= 4268) and without (n = 2562) childhood trauma. Treatment effects across the studies were standardized by calculating effect sizes (Hedges’ g: small effect = 0.2, moderate effect = 0.5, and large effect = 0.8). The most common types of childhood trauma were emotional neglect (58%) and emotional abuse (52%), physical abuse (42%) and physical neglect (40%), and sexual abuse (35%). Patients with childhood trauma had more severe symptoms before and after treatment compared with those without childhood trauma. However, during treatment, similar improvements in symptoms were reported in patients with (g = 1.272) and without (g = 1.400) a history of childhood trauma (trauma vs no trauma, g = 0.016; P = .77). No differences in response based on trauma type were observed.

Previous studies showing diminished treatment response in patients with a history of childhood trauma have characterized response categorically in terms of the rates of response and remission. In such study designs, patients with childhood trauma (and greater baseline symptom severity) would need to show greater improvement than those without trauma to meet the response and remission criteria. The present metaanalysis suggests the importance of observing the change in baseline symptom severity and remission rates when assessing treatment response.

Although no single type of trauma showed a greater impact on outcomes than others, many patients had overlapping sources of trauma. Thus, the authors suggested that future meta-analytic research focused on the impact of differing traumatic loads on MDD outcomes may be valuable.
The results of this meta-analysis were based on the acute treatment phase, whereas a history of trauma is associated with residual symptoms and more relapses long-term. Evidence-based treatments should be administered in these high-risk patients, and additional research should address the adverse impact of trauma on MDD over time.