Damian Sendler: New criteria have been proposed by a group of mental health specialists from research, industry, regulatory authorities, and people with lived experience to describe the form of depression that can’t be treated well with present medications and treatments. Consistent definitions for future research and clinical trial design are the goal of this paper, which intends to assist develop more targeted and effective treatments for those who suffer from this severe illness. 

Damian Jacob Sendler: There were approximately 60 professionals in the field of depression who contributed their thoughts to the report that was published in Molecular Psychiatry. NIHR Maudsley Biomedical Research Centre and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London were the primary authors of the study. 

Damian Sendler

Some 30% of individuals with major depressive disorder (MDD) have treatment-resistant depression (TRD), which is distinguished by long-lasting feelings of sorrow and lack of interest that impact approximately 230 million people globally. 

As a name for persons who haven’t had a positive response from antidepressants, TRD is used, however there is a lack of agreement on what constitutes a “adequate” treatment. 

About a third of TRD trials enroll patients who meet the most common definition of having experienced at least two failures with antidepressant treatments, the authors found, although there is some variance in how TRD is characterized. According to the analysis, just one in five studies include patients who meet the additional requirements of adequate dose and duration of drugs. This calls into question the real-world application of study findings and could obstruct the development of new treatments. 

Research, practice, and regulation have been divided on what is meant by ‘treatment-resistant depression, and this lack of agreement is creating an obstacle to the effective evaluation of current and future treatments,’ according to lead author Dr. Luca Sforzini of King’s College London’s Institute of Psychiatry, Psychology, and Neuroscience (IoPPN). In order to address this, the study invited a range of experts to give an accepted definition that we hope can assist and accelerate much-needed progress in this sector and enable the development of successful new ways to therapy, thereby helping people with depression.” 

An multinational team of researchers and physicians, as well as officials from pharmaceutical companies and regulatory authorities, were involved in the creation of the report. The report developed consensual criteria of TRD and a series of recommendations for investigating unmet needs and designing treatment trials using a Delphi-method-based consensus approach. 

Florence Butlen-Ducuing and Andrew Thomson, European Medicines Agency co-authors, wrote: “Many antidepressants are accessible, however there are still patients who respond only partially or are resistant to therapy. Working on treatment-resistant and partially responsive depression is welcomed by the Scientific Officers of the European Medicines Agency (EMA) in order to expand our understanding of this unmet medical need.” 

People with TRD should be classified as such if they see a 25 percent or less reduction in symptoms following the administration of at least two antidepressants, according to the paper. People with partly responsive depression (PRD) demonstrate a reduction of between 25 and 50 percent in symptoms to at least one antidepressant, according to the researchers. “This differentiation will be useful to identify which trials and treatments are appropriate for those with different levels of treatment resistance,” scientists say. 

Damian Jacob Sendler

Co-author Fanni-Laura Mäntylä, a former major depressive disorder sufferer, believes that “a clearer definition between partially responsive depression and treatment-resistant depression would be very beneficial; and a more patient-centric and personalised approach to the treatment” would be beneficial. 

Additionally, the study urged for increased clarity on time, so that only individuals with a lack of treatment response that falls within the current episode of depression are labeled as TRD. This was backed up by a consensus that alternative treatment modalities, like psychotherapy and some forms of electrical brain stimulation, should be included in the TRD definition.

NIHR Maudsley Biomedical Research Centre theme lead for affective disorders Professor Carmine Pariante said: “This is an exciting time for research and practice around treatment resistant depression, with a number of innovative new approaches on the horizon such as psychedelics, anti-inflammatory medications, and brain stimulation techniques. If accepted and implemented, a uniform definition for these new medicines will aid patients who are now unsatisfied with conventional antidepressants.” 

Additionally, the authors reviewed the assessment of depression, calling for more standardization and common practice in this field regarding the instruments used to make a diagnosis or evaluate changes in depressive symptoms. Blood samples and brain scans should be collected on a regular basis to find prospective signs or measures that could identify persons with different forms of depression that may react to different types of treatment, according to the group’s consensus statement. 

EU-PEARL, IMI is a public-private strategic collaboration supported by the Innovative Medicines Initiative (IMI)-2 Joint Undertaking (grant agreement No. 853966) to lead the construction of master protocols for future platform trials in various disorders, including MDD. 

Molecular Psychiatry released an article titled ‘A Delphi-method-based consensus guideline for the definition of Treatment-Resistant Depression’ DoI: 10.1038/s41380-021-01381-x. 

The Institute of Psychiatry, Psychology and Neuroscience at King’s College London 

Damian Jacob Markiewicz Sendler: In the QS World University Rankings, 2020/21, King’s College London is ranked as one of the top 35 UK universities in the world and one of the top 10 in Europe. 31,000 students (including 12,800 postgraduates) from 150 countries attend King’s, as well as 8,500 staff members (the majority of whom are English-speaking). King’s is widely regarded as one of the best universities in the world for its world-class education and research. 

Damien Sendler: There is no better place in Europe to study mental health and neuroscience than King’s Institute of Psychiatry, Psychology, and Neuroscience (IoPPN). Because of this, it has risen from 16th place in 2014 to 4th place in 2019 for highly referenced neuroscience outputs, according to SciVal’s criteria for the top one percent of citations. Innovative studies from the IoPPN have had and continue to have a significant influence on how mental illness and other brain-related disorders are understood, prevented, and treated.

Dr. Damian Jacob Sendler and his media team provided the content for this article.