Unconventional Wisdom: Major Depression Tied to Childhood Trauma Is Treatable

Batya Swift Yasgur, MA, LSW

September 27, 2022

Despite a higher symptom burden, patients with major depressive disorder (MDD) and a history of childhood trauma (CT) can achieve significant recovery following treatment with a combination of pharmacotherapy and psychotherapy, new research suggests.

Results from a meta-analysis of 29 studies from 1966 to 2019, which included almost 7000 adults with MDD, showed that more than 60% reported a history of CT. But despite having more severe depression at baseline, those with CT benefited from active treatment. Effect sizes were comparable, and dropout rates were similar to those of their counterparts without CT.

"Evidence-based psychotherapy and pharmacotherapy should be offered to depressed patients, regardless of their childhood trauma status," lead author Erika Kuzminskaite, MSc, a PhD candidate at Amsterdam UMC Department of Psychiatry, the Netherlands, told Medscape Medical News.

"Screening for childhood trauma is important to identify individuals at risk for more severe course of the disorder and post-treatment residual symptoms," she added.

The study was published online September 22 in The Lancet Psychiatry.

Common and Potent Risk Factor

The researchers note that CT is common and is potent risk factor for depression. Previous studies have "consistently indicated significantly higher severity and persistence of depressive symptoms in adult patients with depression and a history of childhood trauma."

Previous individual and meta-analytic studies "indicated poorer response to first-line depression treatments in patients with childhood trauma, compared to those without trauma, suggesting the need for new personalized treatments for depressed patients with childhood trauma history," Kuzminskaite said.

"However, the evidence on poorer treatment outcomes has not been definitive, and a comprehensive meta-analysis of available findings has been lacking," she added.

The previous meta-analyses showed high between-study heterogeneity, and some primary studies reported similar or even superior improvement for patients with CT, compared to those without such history, following treatment with evidence-based psychotherapy or pharmacotherapy.

Previous studies also did not investigate the "relative contribution of different childhood trauma types."

To address this gap, investigators in the Childhood Trauma Meta-Analysis Study Group conducted the "largest and most comprehensive study of available evidence examining the effects of childhood trauma of the efficacy and effectiveness of first-line treatments for adults with MDD."

To be included, a study had to focus on adults aged ≥18 years who had received a primary diagnosis of depression. The study had to have included an available assessment of childhood trauma, and patients were required to have undergone psychotherapy and/or pharmacotherapy for depression alone or in combination with other guideline-recommended treatments. Studies were also required to have a comparator group, when applicable, and to have reported depression severity before and after the acute treatment phase.

Of 10,505 publications, 54 trials met inclusion criteria; of these, 29 (20 randomized controlled trials and nine open trials), encompassing 6830 participants aged 18 – 85 years, included data that had been made available by authors of the various studies and were included in the current analysis.

Most studies focused on MDD; 11 trials focused on patients with chronic or treatment-resistant depression.

The primary outcome was "depression severity change from baseline to the end of the acute treatment phase" (expressed as standardized effect size — Hedges' g).

Greater Treatment Motivation?

Of the included patients, 62% reported a history of CT. They were found to have more severe depression at baseline, compared to those without CT (g = .202; 95% CI, 0.145 – 0.258; I² = 0%).

The benefits from active treatment obtained by these patients with CT were similar to the benefits obtained by their counterparts without CT (between-group treatment effect difference: g = .016; 95% CI, -0.094 – 0.125; I² = 44.3%).

No significant difference in active treatment effects (in comparison with control condition) was found between individuals with and those without CT (g = .605; 95% CI, 0.294 – 0.916; I² = 58.0%; and g = .178; 95% CI, -0.195 to 0.552; I² = 67.5%, respectively; between-group difference P = .051).

Dropout rates were similar for the participants with and those without CT (risk ratio, 1.063; 95% CI, 0.945 – 1.195; = 0%).

"Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length," the authors report.

The findings did, however, differ by country, with North American studies showing larger treatment effects for patients with CT, compared to studies conducted in Asian-Pacific countries (g = 0.150; 95% CI, 0.030 – 0.269; vs g = 0.255; 95% CI, -0.508 to -0.002, respectively; corrected false discovery rate, 0.0080). "However, because of limited power, these findings should be interpreted with caution," the authors warn.

"It could be a chance finding and is certainly not causal," Kuzminskaite suggested.

Most studies (21 of the 29) had a "moderate to high risk of bias." But when the researchers conducted a sensitivity analysis in the low-bias studies, they found that results were similar to those of the primary analysis that included all the studies.

"Treatments were similarly effective for patients with and without childhood trauma, with slightly larger active treatment (vs control condition — placebo, wait list, care-as-usual) effects for patients with childhood trauma history," Kuzminskaite said.

"Some evidence suggests that patients with childhood trauma are characterized by greater treatment motivation," she noted. Moreover, "they are also more severely depressed prior to treatment [and] thus have more room for improvement."

"Hopeful Message"

Commenting for Medscape Medical News, Yvette Sheline, MD, McLure professor of psychiatry, radiology, and neurology and director of the Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Perelman School of Medicine, Philadelphia, called it a "well-executed" and "straightforward" study "with clear-cut findings."

Sheline, the director of the Section on Mood, Anxiety, and Trauma, who was not involved with the study, agrees with the authors' conclusions — "to use evidence-based treatments for depression in all patients," with or without a history of CT.

In an accompanying editorial, Antoine Yrondi, MD, PhD, of Université de Toulouse, in Toulouse, France, called the findings "important and encouraging" but cautioned that CT could be associated with conditions other than depression, which could make MDD "more difficult to treat."

Nevertheless, the meta-analysis "delivers a hopeful message to patients with childhood trauma that evidence-based psychotherapy and pharmacotherapy could improve depressive symptoms," Yrondi said.

Yrondi encouraged physicians not to neglect CT in patients with MDD. "For this, it is important that physicians are trained to evaluate childhood trauma and to take it into account in their daily practice."

No source of funding for the study was listed. The authors and Sheline have disclosed no relevant financial relationships. Yrondi has received speaker's honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, and Jazz and has carried out clinical studies in relation to the development of a medicine for Janssen and Lundbeck that are unrelated to this work.

Lancet Psychiatry. Published online September 22, 2022. Abstract, Editorial

Batya Swift Yasgur MA, LSW is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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