Inflammation and Depression: What’s the Connection?
- Tammy Johnson, PMHNP-BC
- Sep 4
- 2 min read
When we think about depression, we often focus on brain chemistry, emotions, or life stress. But in recent years, research has shown that inflammation in the body may also play an important role in mood and mental health. For some people, depression is not just “in the mind”—it may also be connected to the immune system.
What Do We Mean by Inflammation?
Inflammation is the body’s way of protecting itself when fighting off illness or injury. But when inflammation stays elevated over time, it can disrupt many systems in the body—including the brain.
We can measure inflammation with a blood test called CRP (C-reactive protein):
Low inflammation: less than 1 mg/L
Moderate inflammation: 1–3 mg/L
High inflammation: more than 3 mg/L
High levels of inflammation have been linked with a higher risk of depression and with making some antidepressants less effective.
What conditions are associated with inflammation besides depression?
Obesityb
Insulin resistance
Autoimmune disease
Allergies
Cardiovascular disease
Irritable bowel disease
Certain cancers
How Does This Affect Treatment?
If inflammation is a factor, depression may respond differently to certain treatments. Here’s what research suggests:
Medications:
Traditional SSRIs (like sertraline, fluoxetine, escitalopram) may work better when inflammation is low.
In higher inflammation, people often do better when SSRIs are combined with bupropion, which boosts dopamine.
Other medications that may help target both mood and inflammation include bupropion, vortioxetine (Trintellix), stimulants, lithium, ketamine, lurasidone, lumateperone, and cariprazine.
Lifestyle approaches: Lifestyle changes can lower inflammation while also improving mood:
Regular movement and exercise
Quality sleep and sleep hygiene
Meditation or yoga (which calm the nervous system)
Treating underlying health conditions and infections
Following an anti-inflammatory or Mediterranean-style diet (rich in fruits, vegetables, whole grains, fish, and healthy fats)
Supplements: Certain supplements may support brain health and reduce inflammation, including L-methylfolate and omega-3 fatty acids.
Why This Matters
Not all depression looks the same—and not all treatment works the same for everyone. Understanding the role of inflammation helps explain why some people don’t feel better on standard antidepressants alone. A more personalized approach—looking at brain chemistry, the immune system, lifestyle, and whole-body health—can often lead to better results.
The Bottom Line
Depression is complex, and inflammation may be one piece of the puzzle. If you’ve tried standard treatments without success, it may be worth asking your provider whether inflammation could be playing a role. The good news: there are many tools available—from lifestyle strategies to medications—that can help both the brain and body heal.
Tammy Johnson is a PMHNP at Something Human Mental Health. Along with her many interests, she has gone on to receive extra training and education in women's psychiatric health and perinatal prescribing from Postpartum Support International. She has a passion for holistic, whole person centered care throughout the lifespan.
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