“These findings have clear implications for NHS treatment recommendations. Treatment-resistant depression is a common, potentially severe and life-changing illness that, by its nature, is difficult to treat with the medications we currently have available."
Professor Anthony Cleare, Professor of Psychopharmacology & Affective Disorders at King’s IoPPN and the study’s lead author
19 March 2025
Quetiapine augmentation found to be more clinically and cost-effective for treatment-resistant depression compared to lithium
New research has found that quetiapine augmentation – a treatment for depression in people that have't fully responded to antidepressants – is both more effective at reducing depression and more cost-effective than the older and commonly used alternative lithium.
The research, published in Lancet Psychiatry, is the first study to compare the two drugs over an extended period of time, which researchers hope will influence future NHS treatment recommendations.
The Lithium versus Quetiapine in Depression (LQD) Study enrolled patients with treatment-resistant depression (TRD), a condition characterised by a failure to respond to standard antidepressants, and which affects up to a third of patients with depression – an estimated 2.7 million people in the UK and 100 million people worldwide. Augmentation, which adds an additional drug to antidepressant therapy, is a recommended treatment strategy for individuals with TRD. Prior to this study however, there was little evidence comparing different augmentation options head-to-head.
212 adult participants with major depressive disorder who had not responded to at least two different antidepressants were randomly assigned to receive either quetiapine (107) or lithium (105) augmentation. Researchers tracked the severity of their symptoms over the course of 12 months, while an economic analysis compared the cost-effectiveness to both the NHS and personal social services.
At the end of the 12-month period, researchers found that the quetiapine arm showed a greater reduction in the severity of self-reported depression symptoms compared to the lithium group, as well as less self-reported functional impairment, and at a reduced cost to the NHS and social care systems.
Professor Anthony Cleare, Professor of Psychopharmacology & Affective Disorders at King’s IoPPN and the study’s lead author said, "This study is the first to directly compare quetiapine with lithium over an extended period of time and provides a robust argument for quetiapine’s use. Importantly, since many individuals with treatment-resistant depression experience long term, often fluctuating symptoms, the study assessed patients weekly over the course of a year and found that the benefits of quetiapine persisted across the whole period."
Despite the favourable findings for quetiapine, the researchers stress that lithium remains an effective treatment for many people, and can reduce the risk of suicidality and relapse in mental illness.
Dr Jess Kerr-Gaffney, a coauthor of the research, said, “The treatment of depression can be complex, and different therapies will affect people in different ways. Future research will hopefully help us to predict treatment response, as well as explore whether there are additional factors which may guide treatment choice in a more personalised manner.”
Prof Cleare added, “Despite the effectiveness of augmentation treatments, very few patients with treatment resistant depression actually receive them (less than 2% according to one recent study of UK GPs). Improved education, training and support is needed to improve access to these treatments in the NHS.”
This research was funded by the NIHR Health Technology Assessment (HTA) programme (14/222/02).
Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment resistant depression (LQD): A pragmatic parallel randomised controlled superiority trial in the UK (Anthony J Cleare, Jess Kerr-Gaffney, Kimberley Goldsmith, Zohra Zenasni, Nahel Yaziji, Huajie Jin, Alessandro Colasanti, John R Geddes, David Kessler, R Hamish McAllister-Williams, Allan H Young, Alvaro Barrera, Lindsey Marwood, Rachael W Taylor, Helena Tee, and the LQD Study Group) (DOI10.1016/S2215-0366(25)00028-8) was published in Lancet Psychiatry.
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Professor of Psychopharmacology & Affective Disorders
Research Associate
Professor of Medical Statistics and Complex Intervention Methodology
Senior Lecturer in Health Economics
Professor of Psychological Medicine
Research Associate