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Research suggests a relationship between clinical depression and increased inflammation. The interleukin-6 molecule, which has proinflammatory (cytokine) and anti inflammatory (myokine) properties seems to play a role in increasing inflammation in patients experiencing depression. Patients with depression have higher inflammatory markers, leading researchers to study factors that indicate inflammatory pathways and treating depression by addressing inflammation.

A recent study in The British Journal of Psychiatry noted that oral ketamine reduced depressive symptoms in a small sample of people with treatment-resistant depression. And previous research done with mice demonstrated that ketamine can impact depressive behaviors by decreasing inflammatory cytokines. Initially used as an anesthetic, ketamine can reduce pain in lower doses and more recently work has been evaluated for use in reducing depressive symptoms. It potentially offers fast treatment for patients who are discouraged by the failure rate of other traditional methods and the extended time it takes for many pharmaceuticals to work. 

Kalypso Wellness Centers is one facility focused on addressing the role of inflammation in depression by treating patients with ketamine. Co-Founders Dr. Bryan Clifton and Dr. Cannon Clifton, both board certified anesthesiologists and pain management physicians view ketamine as a very potent anti-inflammatory agent.  Since depression has an inflammatory component, they report “high efficacy rates [with ketamine] for chronic depression, bipolar disorder and PTSD." Ketamine works by blocking “pain receptors that none of the ‘morphine type’ of drugs block” as well as blocking an excitatory receptor in the brain. They note “this is key for all mental health issues as the brain never gets a chance to rest since this excitatory receptor is going too much.”

Other physicians, such as Dr. Barry Sears, address inflammation through nutrition and supplements. Sears, a leading authority in anti-inflammatory nutrition, author of the Zone Diet book series, and president of the non-profit, Inflammation Research Foundation, notes that correlations are only valid if a reduction in depression occurs in conjunction with a reduction of inflammation. He points to studies that use high-dose fish oil as a method to reduce inflammation and therefore also reduce depressive symptoms. But not any fish oil will benefit those with depression, stating his “published research further indicates that high-dose fish oil (15 grams of EPA and DHA) per day is significantly better than low-dose fish oil (2.4 grams of EPA and DHA) in treating major depression in children.”

Sears also studied the importance of the ratio of AA and EPA, two essential acids found in our blood, which are markers of inflammation.  When this ratio is higher, the level of depression is more severe. Studies with children revealed their “AA/EPA ratios were extraordinarily high”, said Sears, and that the “the benefits of fish oil seem to be mainly confined to the EPA level, not the DHA levels in the fish oil.”  This does not discount other properties of fish oil. Rather, it highlights components specific to reducing inflammation and benefiting those with treatment resistant depression.

When it comes to treating depression by treating inflammation, further investigation is needed since some research studies on the relationship are done with small sample sizes. However, though the association between raised inflammatory markers and depression may be small, there is enough to support a correlation between inflammation and depressive disorder.  

Initial findings from studies in this area offer hope to patients who perhaps feel their depression is not treatable due to not experiencing improvement with traditional pharmaceuticals. Treating the inflammation may result in fewer potential side effects than what a patient may experience with medication. Whether ketamine, fish oil, or another solution holds the answer, it is encouraging to see providers exploring non-traditional treatment techniques for a mental illness that affects a significant part of the population.