Major challenges in youth psychopathology: treatment-resistant depression. A narrative review.

Major depressive disorder (MDD) is a major health issue in adolescents and young adults, causing high disability and impairing functioning. Its clinical presentation can differ from that in adults, and standard antidepressant treatments often yield suboptimal responses. About 40% of youths with MDD experience treatment-resistant depression (TRD), which is linked to higher rates of comorbid conditions and suicidality. Various biological, environmental, and clinical factors contribute to TRD, which may also signal an unrecognized bipolar disorder, complicating diagnosis. This review summarizes evidence on TRD's epidemiology and clinical features in this age group and discusses possible treatments, including novel fast-acting antidepressants. These drugs show promise but require careful risk-benefit assessment within integrated care models.

Study at a glance

Abstract

Major depressive disorder (MDD) represents a major health issue in adolescents and young adults, leading to high levels of disability and profoundly impacting overall functioning. The clinical presentation of MDD in this vulnerable age group may slightly differ from what can be observed in adult populations, and psychopharmacological strategies do not always lead to optimal response. Resistance to antidepressant treatment has a prevalence estimated around 40% in youths suffering from MDD and is associated with higher comorbidity rates and suicidality. Several factors, encompassing biological, environmental, and clinical features, may contribute to the emergence of treatment-resistant depression (TRD) in adolescents and young adults. Furthermore, TRD may underpin the presence of an unrecognized bipolar diathesis, increasing the overall complexity of the clinical picture and posing major differential diagnosis challenges in the clinical practice. After summarizing current evidence on epidemiological and clinical correlates of TRD in adolescents and young adults, the present review also provides an overview of possible treatment strategies, including novel fast-acting antidepressants. Despite these pharmacological agents are promising in this population, their usage is expected to rely on risk-benefit ratio and to be considered in the context of integrated models of care.