Inflammation and Depression Revisited

What is Inflammation?

It can be defined as the body’s natural response to infection or injury. Inflammation can be a good thing and is essential for survival. We also know that chronic inflammation is bad. It’s known to contribute to heart disease, cancer, and neurodegenerative disorders. 

What can we say about depression and inflammation?

Some patients with depression have elevated inflammatory markers. In cardiology, C-reactive protein (CRP) is used as a marker to help predict the risk of cardiovascular disease. Obesity is known to be correlated with inflammation and can result in elevated CRP. The standard American diet contributes to both inflammation and obesity. CRP has also been used in psychiatry, but it’s less clear how to use this to predict risk or severity of depression.

Evidence for the treatment of patients with depression and inflammation

The current recommendation to determine if significant inflammation is present, is to order a high-sensitivity CRP test. The exact cutoff value to indicate significant inflammation is not clear. Somewhere between 1 mg/L and 3 mg/L is a reasonable reference range. We can look to the literature to guide us. There are a few randomized controlled trials available. One such trail in the American Journal of Psychiatry compared escitalopram (Lexapro) to nortriptyline in 241 patients. Patients with high CRP > 3 mg/L did better on Nortriptyline and patients with low CRP 1 mg/L did better on escitalopram (GENDEP Trial). Another trial looked at the use of bupropion (Wellbutrin) as augmentation for 106 patients with major depression currently on escitalopram. Bupropion improved depression for those with a CRP > 1 mg/L (CO-MED Trial). A common factor is both nortriptyline and bupropion have an effect on dopamine. The precise reason that increased dopamine levels seems to improve depression in patients with inflammation is unclear. However, this provides some evidence and can inform treatment decisions.

Pharmacotherapy for patients with depression and inflammation

  1. Nortriptyline: If the patient has a CRP >3 there is evidence to support the use over SSRIs specifically escitalopram from GENDEP Trial
  2. Bupropion: For patients with CRP >1 or obesity augmentation with bupropion may improve depressive symptoms. 
  3. Lurasidone: commonly used to treat bipolar depression, has some evidence to support its use when CRP > 2 
  4. Pramipexole: has some evidence to support its use in animal models, and off label use in treatment resistant depression

Final Notes

I do not believe all of these new insights into inflammation and depression are ready to be considered standard of care in psychiatry. For patients struggling with obesity, are treatment resistant, or had a poor response to initial antidepressant treatment may benefit from ordering a CRP level and letting it help guide medications choices. Like most things in science more research is required, but inflammation remains an interesting target for depression treatment. 

4 thoughts on “Inflammation and Depression Revisited

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  1. Interesting research. Certainly the benefits of a well balanced diet and exercise are strongly linked to helping treat symptoms of depression – I wonder if that’s linked to inflammation as you suggest. Thanks for sharing

    1. There is a lot of good research coming out about the the impact of diet and exercise on mental health. We are in the beginning stages of applying lifestyle medicine to psychiatry. I always tell patients to control the aspects of health that they can. Diet and exercise are two easy ways to improve overall health that are under each persons direct control. We appreciate you reading and feel free to let us know what topics you would like to see covered in the world of mental health.

      1. Thanks for taking the time to reply. Since you asked – I’m very interested in use of drugs such as MDMA in drug assisted psychotherapy to treat PTSD and anxiety in particular (having suffered from issues with both in the past).

      2. With any of these drugs psilocybin, MDMA, ketamine, it’s always an issue conducting the research. Even Cannabis for all the antidotal benefits we cannot perform the proper research with the federal government restrictions to confirm these benefits. I too am excited and believe we need to use all available options in treatment. Hopefully more people start to feel this way and if there is a strong desire on the part of the general population that will help move things forward.

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