How can depression treatment be improved and what is medication and therapy resistance? A new study calls for more refined research for people experiencing this mental health condition.
A group of mental health experts from research, industry, regulatory bodies and with lived experience have proposed new agreed criteria for depression treatment for individuals who do not respond to medication and therapies effectively.
The new report aims to provide consistent definitions for future research, and especially for designing clinical trials for new medications, to help develop more tailored and effective depression treatments for people experiencing this disorder.
Published in Molecular Psychiatry, the report used a well-known method to gain consensus, the Delphi Method, which collected and summarised the views of over 60 experts in the field of depression.
Resistance to depression treatment
Treatment-resistant depression (TRD) affects up to 30% of adults with major depressive disorder, a clinical condition characterised by persistent feelings of sadness and loss of interest experienced by 230 million people worldwide.
The term TRD describes those individuals who have not responded to ‘adequate’ depression treatment, but there is a lack of consensus around the concept and what is understood by ‘adequate’ treatments.
The researchers found there is a variation around how TRD is defined and that only about a third of studies in TRD enrol participants who met the most common definition of having experienced at least two failures with depression treatment approaches. Additionally, only one in five studies enrolled participants who met the additional criteria of adequate dose and duration of medications. This questions the applicability of the results from research to the real world and potentially hinders progress in the development of novel treatments.
First author Dr Luca Sforzini from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said: “So far there has been confusion about what is meant by treatment-resistant depression in research, practice and regulation, and the lack of a shared understanding is creating a barrier to effectively assessing current and future treatments. To address this, the report convened a range of experts to provide an agreed definition that we hope can support and accelerate much-needed progress in this field and enable the development of effective new approaches to treatment, eventually helping people with depression.”
The Delphi-method-based approach
The researchers used a Delphi-method-based consensus approach and formulated agreed definitions of TRD and a set of recommendations on researching unmet needs and designing clinical trials.
Co-authors from the European Medicines Agency, Florence Butlen-Ducuing and Andrew Thomson, said: “Many antidepressants are available, but there are still patients who are responding only partially or are resistant to treatments. As Scientific Officers of the European Medicines Agency, we welcome work that can improve our understanding of treatment-resistant depression and partially responsive depression and guide better clinical trials to try and address this unmet medical need.”
The report recommended a clearer definition of TRD should be adopted: this would classify people as having TRD when they experience a minimal reduction in symptoms (by 25% or less) after the use of at least two antidepressants. Furthermore, they suggested a distinction between TRD and partially responsive depression (PRD), where people with PRD show a reduction of between 25 to 50% in symptoms to at least one depression treatment. This differentiation between these levels of treatment resistance will be useful to identify who will be appropriate for certain trials and eventually for treatments, according to the authors.
In the case of TRD, the study called for greater clarity around timing, so only those with a lack of depression treatment response falling within the current episode of depression are diagnosed with TRD. The authors agreed that the TRD definition should be as inclusive as possible in terms of other types of treatments so that it does not exclude people who have failed psychotherapy or some brain stimulation techniques.
Lead author, Professor Carmine Pariante from the IoPPN and theme lead for affective disorders at the NIHR Maudsley Biomedical Research Centre, said: “This is a very exciting time for research and practice around treatment-resistant depression, with several innovative new approaches on the horizon such as psychedelics, anti-inflammatory medications and brain stimulation techniques. We hope our report will pave the way for the acceptance and implementation of a standard definition to ensure these new therapies work effectively in patients who are not currently helped by available antidepressants.”
The authors also discussed the assessment of depression and called for more standardisation and shared practice in this area in terms of which instruments are used to provide a diagnosis or assess change in depressive symptoms. They agreed that the collection of biological data, such as blood samples and brain scans, should be done consistently to identify possible markers or measures that could identify people with different forms of depression that may respond to different types of treatment.
