King's College London

LQD study key points

• The LQD study compared lithium and quetiapine in treatment-resistant depression (also known as difficult-to-treat depression).

• Lithium and quetiapine were added onto patients’ current antidepressant.

• Both groups improved, but quetiapine improved depression symptoms better than lithium – a difference that was maintained over one year.

• Both groups had similar side effects.

• Adding on a medication like quetiapine or lithium could be beneficial for many people with difficult-to-treat depression.

What is difficult-to-treat depression?

Many people suffer from depression. It is a very common illness, affecting millions of people worldwide. There are lots of different treatments for depression, and these are effective for many people. For some, however, treatments for depression don’t work as well, or they might not work at all. Sometimes they work, but then symptoms of depression come back.

We call this type of depression treatment-resistant depression, or difficult-to-treat depression, and it affects up to 50% of people with depression. It is estimated that there are 2.7 million people in the UK with difficult-to-treat depression, and 100 million worldwide.

How is difficult-to-treat depression treated?

There are lots of different options for treatment, including different types of psychological therapy, medications, neurostimulation (using magnets or electricity to stimulate specific areas of the brain), and lifestyle changes such as exercise, sleep or mindfulness.

What are lithium and quetiapine, and how are they used in difficult-to-treat depression?

Lithium and quetiapine are two drugs that are used to treat several different mental health conditions. There is some evidence that adding another type of medication to an antidepressant could help reduce symptoms of depression. For treating difficult-to-treat depression, the NHS recommends that a medication like lithium or quetiapine is added to an antidepressant.

What did the LQD study look at?

This study looked at whether adding lithium or adding quetiapine to antidepressant treatment was better at reducing symptoms of depression.

Why is this important?

Both treatments are effective at treating difficult-to-treat depression, but these two common add-on treatments had not been compared before in a long-term study. We wanted to see which treatment was better over a long period of time (52 weeks).

How did the LQD study compare these two medications?

We looked at patients with difficult-to-treat depression across England and followed them over a year. Patients recorded their mood each week at home, and also came to the research site for several visits over the year. In these visits, we looked at how they were feeling, their depression and anxiety, their functioning (e.g. at work, or in leisure activities), general health, and some thinking skills. With this data, we were able to compare the people taking lithium and the people taking quetiapine over 52 weeks.

What were the results of the LQD study?

• Quetiapine improved depression symptoms in patients better than lithium.
• Patients said that their functioning improved in areas such as home, leisure, work, and relationships, as well as their overall quality of life.
• Both groups had similar side effects. Many patients felt the benefits of these medication outweighed any negatives.
• After calculating the overall costs and benefits of using both treatments in the NHS, we found that quetiapine was the more cost-effective option – an important consideration given the pressures on the NHS budget.

What now?

Adding on a medication like quetiapine – or lithium – could be beneficial for many people with difficult-to-treat depression, and they are both safe and effective treatments. However, both of these medications are underused to treat difficult-to-treat depression. We think it is important that more patients have access to treatments that could help them, and that patients know that there are many options, including lithium and quetiapine, that could help them.

Additional reading and events

For everyone

• Read our blog post for The Mental Elf
• Read our press release about the LQD study research findings

For researchers, clinicians and policymakers

• Sign up for our October 2025 webinar: New hope for difficult-to-treat depression: the evidence you need now
• Register for the International Society for Affective Disorders: 2025 Regional Meeting
• Read the main paper in the Lancet: Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment-resistant depression

• Read the research paper in the Journal of Pyschopharmacology: Patient perspectives of lithium and quetiapine augmentation treatment in treatment-resistant depression

• Read the study protocol for the LQD study

• Read the NIHR report on the Clinical and cost-effectiveness of the LQD Study

• Read the BJPsych Open article: A retrospective examination of care pathways in individuals with treatment-resistant depression