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Inflammation: True Cause of Depression? Evidence and Research Directions

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If you take antidepressants but still feel depressed, you're in the majority, according to References 1 and 2. Both claim that only one third of depressed patients get remission of symptoms from their first course of medication. The advertisements for Abilify(R), an anti-psychotic drug, echo these data. The manufacturer encourages patients to take their drug as an add-on for antidepressant treatment that is not working.

Reference 1 suggests a different approach. This review article presents evidence for inflammation as the cause of depression in a subgroup of patients diagnosed with major depressive disorder, with or without other inflammatory diagnoses.

Inflammatory markers in depression. A subgroup of patients with depression has elevated levels of the pro-inflammatory molecules interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, and C-reactive protein. These levels decrease with antidepressant treatment. This is one possible explanation for why it takes two to four weeks for antidepressants to take effect. The serotonin reuptake inhibitors such as Prozac have the ability to increase serotonin in the neural synapses immediately, and side effects such as nausea occur immediately, but relief of depressive symptoms takes much longer. Perhaps the effect on depression is the result of a change in the inflammatory process.

Drugs and other chemicals that increase inflammation also cause depression. These include:
1. Interferon-alpha, used as a treatment for hepatitis C.
2. Salmonella typhi vaccine.
3. Endotoxin, a cell wall component of gram-negative bacteria. This has been shown to cause depressive symptoms in both humans and rodents.

Inflammatory disorders are associated with an increased prevalence of depression. These include:
1. Diabetes
2. Coronary artery disease
3. Crohn's disease
4. Rheumatoid arthritis
5. HIV infection
6. Cancer
7. Multiple sclerosis

Anti-inflammatory drugs have antidepressant effects. Clinical trials have shown good results in reducing depressive symptoms from:
1. Celecoxib (Celebrex),
2. Etanercept (Enbrel).

Reference 2 states: “There is an unmet need for faster, better, and safer medications” to treat depression. It suggests a stronger focus on “biological components” of the disorder. Inflammation, according to Reference 1, may be the component we all need to look at.

References:

1. McNally L et al, “Inflammation, glutamate, and glia in depression: A literature review”, CNS Spectr 2008 Jun; 13(6): 501- 10.

2. Gelenberg AJ et al, “The history and current state of antidepressant clinical trial design: A call to action for proof-of-concept Studies”, J Clin Psychiatry 2008 Oct; 69(10): 1513- 28.

3. Abilify drug information:
http://www.abilify.com/

Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.

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Linda Fugate PhD
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We value and respect our HERWriters' experiences, but everyone is different. Many of our writers are speaking from personal experience, and what's worked for them may not work for you. Their articles are not a substitute for medical advice, although we hope you can gain knowledge from their insight.

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