News & Latest 05.06.2023

Steps towards more effective therapies for treatment-resistant depression

The i-VALiD project is collecting evidence to help improve mental health services for treatment-resistant depression, which poses a major challenge for healthcare services and the patients it affects. This project has published two papers so far: one explores the patient perspective in treatment, and the other reviews how relevant therapies are evaluated economically.

Depression is a leading cause of global disability and affects millions of adults worldwide. Antidepressant medications are recommended as first-line treatments for those experiencing moderate to severe depression by NICE. However, 30% do not recover after receiving multiple treatments, including support from specialist mental health services. This can be due to not all patients receiving effective treatments and care plans that meet their needs, which has a significant impact on the lives of patients, their carers and family members.

To date, there has been limited research exploring care pathways for depression and treatment-resistant depression across both primary and secondary care. The i-VALID project aims to address this gap by identifying opportunities to provide better interventions at different points in the pathway, using a ‘values-based ’ approach. This approach draws together the best available evidence, clinical expertise, and patient/carer priorities.

Researchers supported by ARC East of England, Cambridgeshire and Peterborough NHS Foundation Trust and Eastern AHSN have published two papers sharing their findings.

Phase one: Exploring the patient’s experiences during treatment

The first publication was a narrative literature review exploring the patient perspective and outcomes in treatment for treatment-resistant depression. NHS commissioning guidance for the development of mental health services emphasises the need for service user involvement and the identification of outcomes measures that are important for them. This study aimed to address this by investigating what outcomes matter to people receiving treatment for treatment-resistant depression, whether current outcome measures reflected this, and if not, how they could be incorporated into the development of a specialist service.

“The study identifies differences in perspectives across treatment timepoints and severity. Given the high rates of treatment-resistant depression and relapse, further research that incorporates patient values is necessary to support recovery and understanding meaningful change for patients.”

Laura Hannah, Clinical Researcher, ARC East of England

Key Findings

A comprehensive review of the literature identified five key themes:

  • Important outcomes beyond recovery from symptoms (including the use of appropriate language in outcome measures).

Improvement of symptoms is not the only outcome that is important to patients. Other areas include, feeling optimistic, self-confidence, being able to cope and understanding. The way that outcomes are measured in practice, may not fully represent what is important for recovery for patients.

  • Differences in patient perspectives across treatment timepoints, depression severity and gender.

Patients who experience several depressive episodes may adapt their treatment goals, and some studies have reported differences in what men and women view as significant features of recovery.

  • Patient preferences.

It’s important that patients feel listened to and that the spectrum of depression is considered. A collaborative care approach between the clinician and patient to establish treatment goals is evidently essential. Patients should be viewed as active agents with unique care objectives, expectations, and values.

  • Identifying essential sets of outcome measures.

Studies looking at essential outcome measures from the perspective of multiple stakeholders suggest that symptom scales such as the PHQ-9 may be useful but should be better combined with measures of functioning and quality of life to fulfil patients’ perspectives.

  • Underdeveloped outcome measures from the patient’s perspective.

There is a lack of research and consensus on suitable outcome measures for persistent depression, including how the interpretation of current outcome measures should be taken with caution. It is recommended that the outcome measures incorporate understanding into the patient’s life.

What do these findings mean?

The views of the patient or towards treatment-resistant depression were not found to be considered in the current standard outcome measures. There was evidence of an overlap between the patients’ and clinicians’ objectives, supporting the idea that the patient perspective supplements and complements the clinicians’ views and current outcome measures. A collaborative care approach between the clinician and patient is crucial to achieving meaningful change.

Given the lack of research and agreement on suitable outcome measures for treatment-resistant depression, specifically incorporating patient values, the authors call for more research in this area. They also highlight the need for “co-production” to enhance the development of evidence-based interventions, policies, and services to meet the needs of those experiencing treatment-resistant depression.

Phase two: How are therapies for treatment-resistant depression evaluated economically?

The second paper provides a systematic review of the economic considerations associated with interventions for treatment-resistant depression. Treatment-resistant depression is common and poses a high cost to healthcare systems, so it is important that resources are put to best use.

The review appraised the existing literature to examine the methods used when evaluating economically viable treatments. Through a systematic review, the research team assessed a broad range of treatments, such as medication, psychotherapy, electroconvulsive therapy, and interventions that are emerging in the UK, including transcranial magnetic stimulation and ketamine infusion therapy.

Against increasingly constrained budgets, it is important we deploy the resources available to us in a way that maximises their benefit. This study has helped us identify key focal points for improving data collection and evidence generation, to ensure that evaluation of future interventions in treatment resistant depression truly and fairly reflect the benefits they deliver.

Rory Cameron, Senior Research Associate, ARC East of England

Key findings

The study found that the economic evidence for interventions in treatment-resistant depression is underdeveloped, particularly for service-level interventions. Considerable variability in study design, methodological quality and evidence sources was found – and as a result there is conflicting evidence as to the cost-effectiveness of key interventions for management of treatment resistant depression. Depression, and in particular treatment resistant depression is characterised by its persistent & recurrent nature, but there was a lack of research exploring the economic evidence beyond (typically), 12-month follow-up periods. Upon review of treatments, it was found that the transcranial magnetic stimulation and electroconvulsive therapy show promise in for a patient’s recovery. However, despite the ten evaluations comparing these approaches, there is no conclusive evidence for their cost-effectiveness and suitability for NHS services.

Next steps

The i-VALiD project has recently welcomed new members with different expertise in computational psychiatry. The next phase aims to use real-world data to map and analyse the care pathway, risk factors, and interventions for treatment-resistant depression in primary and secondary care. This will involve linking de-identified electronic health records (with personal data removed) from primary and secondary care NHS services to better understand how depression and treatment-resistant depression are currently managed, risk factors for depression and treatment-resistant depression, and responses to treatment. The team hopes this will build a better picture of how current resources are being used, and how to optimise care.

An additional piece of work is planned, incorporating focus groups with patients and clinicians to explore their experiences of the pathway. The qualitative work will investigate what clinicians and patients would like to see change and the barriers they have faced. A clinical advisory group and patient and public involvement will be integrated throughout the project.

Find out more about ARC EoE Mental Health Research here.

For queries concerning this article, email ARC East of England Core Team:


The project team included:

Previous involvement