Skip to main content
KBS_Icon_questionmark link-ico

Go to…

Anti-inflammatory drugs do not improve depression in bipolar patients

New research led by King’s College London has shown that two well-known anti-inflammatory drugs do not alleviate depression in patients with bipolar disorder, indicating that inflammation does not play a role in the cause and treatment of bipolar depression and more research is needed to better understand which types of depression could be related to inflammation in the brain.

depression small

Bipolar disorder affects 2% of the population globally and it remains very challenging to treat as there are only three recommended drugs for acute bipolar depression which all have side effects. Several lines of evidence have suggested that a triggering of the immune response in the brain followed by inflammation of the nervous tissue occurs in bipolar disorder, which could provide a potential new alternative target for treatment.

Published in The Lancet Psychiatry the study is the first major clinical trial of the safety and effectiveness of two anti-inflammatory medications, minocycline and celecoxib, at treating depression in adult patients with bipolar disorder. The trial was designed so that neither the participants nor the researchers knew who was getting which treatment and a placebo was given to a control group. All patients continued with their routine clinical care.

The research was a collaboration between King’s College London, the Pakistan Institute of Living and Learning (PILL), Centre for Addiction and Mental Health in Toronto Canada and a number of other institutes and organisations.

In total 224 participants from Pakistan completed the clinical trial and results showed no evidence that either drug produced improvements in measures of depression over 12 weeks. There was a slight but not significant decrease in depression in those who were taking celocoxib whilst those taking minocycline showed a slight but not significant increase in depression. Depression was measured by the 17-item Hamilton Depression Scale.

The main aim of our study was to investigate if inflammation plays a role in both the cause and treatment of bipolar depression and our results indicate that this is not the case since two major anti-inflammatory drugs do not improve levels of depression in this group. Although negative, these results are very important in helping to understand the relationship between depression and inflammation. – Joint senior author Professor Allan Young from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London

The study also showed that there was little difference in the levels of two indicators of inflammation – C-reactive protein (CRP) concentrations and white blood cell count - across the different treatment groups.

There was some variation in the clinical care that the patients were receiving with all of them taking either two or three psychiatric medications. However, when the analysis took this into consideration there was still no evidence that the two anti-inflammatories improved symptoms of depression.

The results argue against the use of anti-inflammatory drugs alongside usual medication to treat bipolar depression. The researchers suggest that before any further trials of similar drugs are done, there needs to be clearer understanding of the mechanisms that underlie the links between inflammation and activity in the brain that causes depression.

Joint senior author Professor Allan Young from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London said: ‘The main aim of our study was to investigate if inflammation plays a role in both the cause and treatment of bipolar depression and our results indicate that this is not the case since two major anti-inflammatory drugs do not improve levels of depression in this group. Although negative, these results are very important in helping to understand the relationship between depression and inflammation.

He continued: ‘The results do not rule out the possibility that inflammatory mechanisms may be important in depression but they do not seem to be involved when the symptoms are part of a bipolar disorder. It may also be possible that there are particular groups who can be defined by inflammatory measures that could benefit from these type of medication and more research is needed to identify these potential groups.’

Our definitive study has indicated that using these drugs in this patient population has no additional benefits compared to standard treatments and that changes in inflammatory markers did not impact whether people got better with anti-inflammatories. We would suggest that more work needs to be done to understand the neurobiology of inflammation in mood disorders before further clinical trials of anti-inflammatory agents can be justified– First author, Dr Ishrat Husain from the Centre for Addiction and Mental Health, University of Toronto

Researchers did highlight that ideally all participants would have been on the same regime of medication throughout the study but this was ethically unfeasible. Ideally the study would also have explored a range of other symptoms and features of bipolar as well as depression and analysed a range of indicators of inflammation, in addition to CRP and white blood cell count. Lastly it must also be considered that the study was conducted in a low to middle income country where diet and other lifestyle factors differ from those in high-income countries so findings may not be generalisable to other countries.

First author, Dr Ishrat Husain from the Centre for Addiction and Mental Health, University of Toronto said: ‘This study is part of an ongoing collaboration that spans three continents, between King's College London and the University of Manchester in the UK, the Centre for Addiction and Mental Health (CAMH) and University of Toronto in Canada and the Pakistan Institute of Living and Learning (PILL) in Pakistan. Professor Young and I have been working with PILL to support research capacity in Pakistan for several years and the completion of this project in sites across the country, has been a testament to the efforts of the PILL team.

'It is the largest trial of anti-inflammatory drugs in bipolar disorder thus far. Several smaller studies had shown that these drugs may be of benefit in treating depression in patients with bipolar disorder. However, our definitive study has indicated that using these drugs in this patient population has no additional benefits compared to standard treatments and that changes in inflammatory markers did not impact whether people got better with anti-inflammatories. We would suggest that more work needs to be done to understand the neurobiology of inflammation in mood disorders before further clinical trials of anti-inflammatory agents can be justified.’

The study was funded by the Stanley Medical Research Institute and the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre.

Reference: Husain, M.I et al.(2020) Minocycline and celecoxib as adjunctive treatments for bipolar depression: a multicentre, factorial design randomised controlled trial. The Lancet Psychiatry.

In this story

Allan Young

Allan Young

Vice Dean (Academic Psychiatry)