In this Research Roundup, we explore new studies on major depressive disorder (MDD).

Esketamine for the Treatment of Adolescents With Major Depressive Disorder and Imminent Suicide Risk

A recent study showed that esketamine combined with comprehensive standard of care rapidly improved depressive symptoms among adolescents with major depressive disorder (MDD) who were at imminent risk for suicide.

In this double-blind randomized controlled clinical trial, investigators compared the effects of esketamine nasal spray (28, 56, or 84 mg) with a psychoactive placebo (midazolam) in 147 adolescents with MDD who were at imminent risk for suicide. All participants also received standard-of-care treatment, including initial hospitalization, oral antidepressant treatment, and evidenced-based psychotherapy. Investigators found that combined 56- and 84-mg doses of esketamine were superior to midazolam in reducing depressive symptoms at 24 hours following the first dose. All 4 treatment groups showed continued improvement in depressive symptoms and severity of suicidality after 4 weeks of treatment. The most common adverse effects reported for participants receving esketamine were dizziness, nausea, dissociation, headache, bitter taste, and sleepiness.

Pooled esketamine doses (56 and 84 mg) showed superiority over midazolam in reducing CDRS-R total score at 24 hours post first dose (between-group difference of least squares means [95% CI]: −5.8 [−11.19, −0.35], P = .037).

Reference

Kosik-Gonzalez C, Fu DJ, Chen LN, et al. Effect of esketamine on depressive symptoms in adolescents with major depressive disorder at imminent suicide risk: a randomized psychoactive-controlled study. J Am Acad Child Adolesc Psychiatry. 2026;65(1):42-55.

Family Psychoeducation for Patients With MDD

According to research, family psychoeducation (FPE) improves depressive symptoms in patients with MDD and enhances the overall well-being of family members. With recent research advances and new pharmacotherapy options for MDD, current evidence on the effectiveness of FPE on key patient outcomes was needed.

A new systematic review aimed to evaluate the evidence on the impact of FPE on antidepressant adherence, which was the primary endpoint, as well as on depressive symptoms, personal recovery, medication beliefs and concerns, and components of FPE for MDD (secondary endpoints). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, investigators searched 5 electronic databases for experimental studies, including randomized controlled trials (RCTs) and nonrandomized trials with pre-post designs; only articles in English that published up to December 13th, 2024, and met the inclusion criteria were included. Investigators assessed the risk of bias in each study using the Joanna Briggs Institute checklist. Of the records identified, 4 (3 RCTs and 1 quasi-experimental study) met the criteria and were included in the review. Investigators utilized a descriptive synthesis of results rather than a meta-analysis, due to the heterogeneous nature of the studies included.

The review highlights a significant gap in research on the relationship between FPE and MDD. Investigators believe further research is needed to evaluate its effectiveness on both clinical and nonclinical outcomes in patients with MDD.

Reference

Obieche O, Tan JYB, Sharma S, et al. Biological aging acceleration in major depressive disorder: a multi-omics analysis. Int J Ment Health Nurs. 2026;35(1):e70205.

The Symptom Structure of MDD and Its Role in Treatment Response

In order to better understand the optimal factor structure of MDD and its role in predicting the response to drug treatment, investigators examined the complex symptomatology of MDD. They found that factor scores may be powerful tools for antidepressant response analysis in patients with MDD.

Investigators performed the 17-item Hamilton Depression Rating Scale (HDRS-17) and Hamilton Anxiety Rating Scale (HARS) on a large sample of 360 patients with MDD and obtained 31-item scores for each patient at baseline. Then, they evaluated the symptom factor structure using exploratory and confirmatory factor analysis. They also analyzed changes in the factor scores after 2, 8, and 26 weeks of antidepressant treatment. Finally, they constructed a logistic regression model to evaluate the predictive efficacy of baseline symptom factors for antidepressant treatment.

Ultimately, they identified an 8-factor model: somatization, depression, sleep, anxiety, libido, insight, appetite, and suicide factors. Depression, suicide, and sleep factor scores showed the most significant changes during antidepressant treatment; while somatization and anxiety factors showed moderate changes; and the scores of appetite, libido, and insight factors showed the most minor changes. Multivariate logistic regression analysis identified sleep, libido, and appetite factors at baseline as independent predictors for symptom remission after 26 weeks of antidepressant treatment. Investigators thus concluded that the 8-factor model is a good fit and is clinically interpretable in MDD.

Reference

Jiang X, Hu Y, Lin C, et al. Unveiling the symptom structure of major depressive disorder and exploring its role in treatment response. J Affect Disord. 2026:392:120072.

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