Abstract

Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options in the U.S. are limited to psychotherapy and two selective serotonin reuptake inhibitors approved by the United States Food and Drug Administration. Molecular mechanisms have been shown to play a role in MDD pathogenesis, progression, and response to medication, yet few studies have explored the role of these pathways in pediatric MDD. In this review, we outline the gravity and importance of MDD in pediatric patients, some challenges in diagnosis and treatment, current treatments available for pediatric patients, and research to investigate differences between pediatric and adult MDD. We hope that this review will provide an outline of the current understanding and treatment of MDD in pediatric patients, and provide thoughtful insights for future work that could advance our understanding of MDD in pediatric populations, and also identify new therapeutic strategies.

Highlights

  • Major depressive disorder (MDD)—the leading cause of disability worldwide [1]—is characterized by depressed mood, low self-worth, and altered sleep and appetite [1]

  • Other medications that are used to treat adults with MDD are not recommended for treatment of pediatric MDD because of serious adverse events, or because there is no evidence of relief from MDD

  • This review has outlined the current understanding of pediatric MDD and the therapeutic options that are available for treatment

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Summary

Introduction

Major depressive disorder (MDD)—the leading cause of disability worldwide [1]—is characterized by depressed mood, low self-worth, and altered sleep and appetite [1]. MDD is highly correlated with suicidality, which is the third highest cause of death in adolescents worldwide [6]. The gravity of this illness cannot be overstated, since it affects all ages, including pediatric populations, and can result in premature death. The prevalence of pediatric MDD increases with age [8,9] with a spike in MDD diagnosis following puberty. There is growing evidence that a number of different pathways may play a role in the pathogenesis of MDD, including inflammation, immune response, monoamine neurotransmission, the hypothalamic–pituitary–adrenal (HPA) axis, and the gut–brain axis [15,16]. Many of the antidepressants currently in use target monoamine neurotransmission but are not effective in 20–50% of patients [18,19], indicating that these patients may be suffering from symptoms of MDD caused by different molecular mechanisms

Diagnosis of Pediatric MDD
Current Pediatric MDD Treatment
First-Line Therapeutic Approaches for Pediatric MDD Treatment
Pharmacological Therapeutics for Pediatric MDD Treatment
Biomarkers and Pathways of Pediatric MDD
Monoamine Neurotransmission
Stress and the HPA Axis
Inflammation and Immune Response
Neurotrophic Factors
Metabolizing Enzymes
Pathway Interactions
Discussion and Conclusions
Findings
Literature Selection
Full Text
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