New Research: Can Anti-Inflammatory Drugs Treat Depression? Risks and Considerations

Dr. Tracey Marks discusses a paradigm shift in understanding depression, moving beyond simply increasing brain chemicals to exploring factors like brain connectivity and inflammation. She highlights a growing body of research indicating that individuals with depression often exhibit higher levels of inflammatory chemicals, and those with infections or autoimmune disorders (such as rheumatoid arthritis, lupus, multiple sclerosis, and psoriasis) face an elevated risk of developing depression. This connection has led to investigations into non-steroidal anti-inflammatory drugs (NSAIDs) as a potential treatment.

The podcast details a 2019 study that analyzed several randomized controlled trials, revealing that NSAIDs, particularly celecoxib (Celebrex) at a dose of 200mg twice daily, showed improvement in depression symptoms when used as either an add-on agent or monotherapy. The mechanism involves NSAIDs blocking the COX enzyme, which reduces the production of prostaglandins—chemicals contributing to inflammation, pain, and fever. Lower prostaglandin concentrations are associated with reduced inflammation, pain, and potentially, depression. However, the exact causal relationship between inflammation and depression, and which precedes the other, remains unclear, making this a developing area of research.

Despite promising results, Dr. Marks emphasizes significant concerns regarding NSAID use, which currently prevent them from being a mainstream recommendation for depression. Key side effects include an increased risk of gastrointestinal bleeding and serious stomach upset, even with non-chronic use. More critically, many NSAIDs, including Celebrex and the withdrawn Vioxx, are linked to an increased risk of strokes and heart attacks, necessitating a blackbox warning from the FDA. Dr. Marks, adopting a conservative stance, expresses caution due to these severe potential side effects and the burden chronic NSAID use can place on the digestive tract.

Practical advice includes exercising extreme caution when combining NSAIDs with lithium, as NSAIDs can elevate lithium levels, requiring medical consultation and level checks. For long-term use, tapering off NSAIDs after six months is recommended to minimize bleeding risks. Dr. Marks suggests that NSAIDs might be considered for individuals who do not respond adequately to standard add-on treatments for depression, but stresses the importance of discussing this option thoroughly with a doctor to weigh the potential benefits against the considerable risks. The research also briefly notes potential benefits for schizophrenia and bipolar disorder.

"earlier this year I did a video talking about how we look at the cause of depression differently than we did 10 years ago and how that caused calls for it different way of treating depression"

"there's been a growing body of research showing that people who are depressed have higher levels of inflammatory chemicals in the body"

"people with infection and autoimmune disorders have an increased risk of developing depression"

"The results showed improvement in depression with the use of NSAIDs with celecoxib rising to the top as the one that was used the most"

"NSAIDs block the enzyme [ __ ] - that makes prostaglandins"

"with lower concentrations of prostaglandins you get less inflammation less pain and less depression"

"we don't have a complete understanding of how inflammation actually causes depression or vice versa and it's not clear which comes first"

"NSAIDs increase the risk of gastrointestinal bleeding"

"many of the NSAIDs like celebrex and Vioxx cause an increase in strokes and heart attacks"

"a blackbox warning is a warning issued by the FDA and required to go on the package information"

"you want to be super careful if you're taking NSAIDs and you're on lithium as in sets can increase lithium levels"

"I would be more inclined to give it a try in someone who's not responding well enough to the standard add-on agents that we usually use"