This Research Topic is the second volume of the Research Topic "Treatment Resistant Depression (TRD): epidemiology, clinic, burden and treatment". Please see the first volume here. Treatment-Resistant Depression (TRD) presents a complex challenge, significantly impacting people with depression, clinicians, and healthcare systems. Affecting 30-40% of those treated with antidepressants, the prevalence and management of TRD, particularly in bipolar depression, require deeper exploration.

People with depression and caregivers face increased disability and reduced quality of life due to treatment resistance. While traditional therapies, such as augmentation strategies and psychotherapy, remain widely used, emerging treatments—including brain stimulation and psychedelic-derived drugs—are expanding treatment options. Notably, esketamine is already licensed for use in many countries, whereas other psychedelics (such as psilocybin) are still being evaluated in clinical trials.

This Research Topic aims to consolidate cutting-edge research in the TRD domain, addressing clinical, epidemiological, and quality of life variables, as well as traditional and novel treatments. It seeks to answer pivotal questions regarding the effectiveness of emerging treatments and the comprehensive impact of TRD on the lives of people with depression. By fostering diverse academic contributions, the Research Topic seeks papers which expand understanding and provide fresh perspectives on TRD, including pivotal studies on emerging pharmacological treatments and groundbreaking therapies.

To gather further insights into the broad spectrum of TRD, this Research Topic welcomes articles addressing, but not limited to, the following themes:

- Clinical definition and diagnostic characterization of unipolar and/or bipolar TRD
- Implications of comorbid psychiatric or medical conditions on the clinical diagnosis of TRD
- Epidemiological findings on TRD, including quality of life of people with depression, family burden and stigma, social isolation or other psychosocial dimensions
- TRD treatment options, spanning traditional strategies and novel psychedelic-derived drugs
- Efficacy and innovations in psychotherapy interventions, including integration of digital health technologies/telepsychology, novel therapeutic frameworks and comparative studies of psychotherapeutic modalities (CBT, DBT, mindfulness etc)
- Advancements in brain stimulation therapies (ECT, TMS, VNS) and other neuromodulatory techniques, including innovations in delivery, safety profiles and selection of individuals for treatment
- Healthcare costs associated with managing unipolar and/or bipolar TRD

Are you interested in contributing a manuscript to this Research Topic?

Treatment Resistant Depression (TRD): epidemiology, clinic, burden and treatment, vol II