Could Anti-Inflammatory Drugs Target Depression?

Data emerges on treating depression with anti-inflammatory medications.

Reviewed by Tyler Woods

Key points

• Inflammation is a contributing factor to depression.
• Pro-inflammatory proteins can affect the brain causing changes linked to psychiatric illness.
• Some anti-inflammatory drugs have shown promise is treating resistant depression.

Inflammation is our body’s defense mechanism against phenomena it recognizes as foreign. However, as with any complicated defense system, errors may occur. Inflammation helps our body fight off bacteria, viruses, and other toxins. If our immune response continues after the threat has passed, it can cause damage to our healthy tissue. Inflammation is linked to many chronic illnesses, such as heart disease, gastrointestinal disorders as well as some neurodegenerative illnesses. In addition, it is implicated in the development of psychiatric diseases.

In 2019, British psychiatrist Edward Bullmore published The Inflamed Mind. He argued depression and other mental illnesses may be due to the activation of our immune systems. Inflammation produces changes in the blood-brain barrier, the protective barrier that separates the brain from the peripheral circulation. This barrier becomes more porous, allowing the entry of proinflammatory proteins. Bullmore argued that when inflammation occurs, proteins called cytokines cross the blood-brain barrier, leading to changes within the brain that cause depression. More recently, research supports the association between inflammation and depression and links the association to elevated levels of pro-inflammatory markers in our peripheral nervous system. This finding is independent of co-occurring physical illness.

In experimental animal models, recurrent stress causes an increase in inflammatory proteins linked to the development of what was perceived as depression in the animals. When scientists inhibited the inflammatory proteins, the depression-like behavior remitted.

Over 9,000 studies have investigated the role of the immune system in depression, particularly the role of inflammation. In fact, this is one of the theories that help to explain why patients with long COVID frequently describe symptoms of major depression.

As a result of this data, researchers are investigating whether anti-inflammatory drugs can be used successfully, either alone or in conjunction with traditional antidepressants, to improve outcomes in patients with depression. Non-steroidal anti-inflammatory drugs have been used in small research trials in patients with arthritis and depression. They reported a significant improvement in depressive symptoms that was unrelated to pain relief. One trial used statin drugs in combination with antidepressants for patients with moderate depression and found a decrease in depressive symptoms after six weeks.

Low motivation is a symptom often seen in patients suffering from major depression. It is frequently described as a feeling of not being driven or excited to start or finish tasks, especially those that are challenging or uninteresting. I can’t even count all the times patients in my office say, “Isn’t there just a pill for motivation?” And to that, I reply, “There isn’t.”

Well, going forward, that may not be true. A study published last week in Nature reported the findings of research that looked at the effect of high levels of inflammation on the development of low motivation. The study enrolled forty-two subjects who were diagnosed with depression and also exhibited high levels of inflammation as measured by a blood test called C-reactive protein. They were randomly divided into two groups. One group of subjects received a single dose of an anti-inflammatory medication used to treat those with arthritis. The other group received a placebo. The researchers studied the subjects for two weeks, during which they were asked to perform various tasks and questionnaires designed to measure motivation levels. The results showed that the group who received the anti-inflammatory drug had an increased willingness to engage in tasks associated with rewards.

What Does This Mean for Future Treatment?

Depression is a debilitating mental health disorder that affects almost 3 million people worldwide and is a leading cause of disability and premature death. The World Health Organization considers depression to be a significant cause of global disease burden and predicts it will be a leading contributor by 2030.

Almost one-third of patients with major depression have treatment-resistant disease. This is defined as a lack of response to adequate antidepressant trials and can be due to many factors, including non-compliance, co-existing substance abuse, and ongoing physical illness. As more research explores the role of inflammation in the development of depression, additional options for treating resistant disease will emerge. Inflammation plays a potential role in the etiology of depression, and anti-inflammatory intervention may represent a novel way of developing more personalized treatment regimens for some patients.

To find a therapist near you, visit the Psychology Today Therapy Directory.