The Body and Mind Connection: The Latest Evidence

Nassir Ghaemi, MD, MPH


June 22, 2015

In This Article

Are NSAIDs Useful for Depression?

The second presenter was Dr Charles Raison, professor of psychiatry and human ecology, University of Wisconsin-Madison. His topic was "Anti-inflammatory Agents as Antidepressants: Truth or Dare?"

Dr Raison cautioned against overenthusiasm for the link between inflammation and mental illness, at least in terms of immediate treatments. His critique referred to a recent meta-analysis[5] that concluded that nonsteroidal anti-inflammatory drugs (NSAIDs), especially celecoxib, may have antidepressant properties. Dr Raison noted that NSAIDs stimulate cadherin-11, a molecule that reduces anxiety in animal models but isn't involved with inflammation processes at all. In addition, serotonin reuptake inhibitors increase some inflammatory cytokines, such as p11, which actually seem to be helpful in animal models of depression response. He noted that the impact of minocycline may have to do with profound effects on gut microbiota, which animal models show have major impact on behavior.

In short, the effects of these agents may have nothing to do with an impact on central nervous system inflammation. We know that inflammation causes depression and that NSAIDs may improve depression in the setting of inflammation, but NSAIDs do not appear to improve depression in medically healthy persons who do not have abnormal inflammation.

Dr Raison then reviewed a key study that he had conducted on infliximab for treatment-resistant depression.[6] Patients who did not have inflammatory diseases were randomly assigned to receive three infusions of infliximab vs saline (at baseline, 6 weeks, and 12 weeks). Over 50% of patients experienced major benefit, and the treatment seemed to have transformed their lives; but when Dr Raison and his colleagues broke the double-blinding, they found that infliximab was equivalent to placebo.

Of note, though, in a subgroup analysis of patients with more inflammation vs less, greater benefit of infliximab was seen in those with higher C-reactive protein levels. If the C-reactive protein level was > 5 mg/L, there was about 3-point improvement on Hamilton Rating Scale for Depression. Infliximab does not enter the central nervous system, so any benefit seen here is based on peripheral inflammation, which is an important hypothesis.

Dr Raison concluded that although there may be a role for some anti-inflammatory agents in some subtypes of depression with evidence of high inflammation, it would be premature to use NSAIDs broadly for depressive states. The benefits are minimal, and the risks are serious: He noted that about 100,000 persons are hospitalized yearly because of NSAID use. Celecoxib more than doubles the risk for myocardial infarction, and about 17,000 persons with rheumatoid arthritis die of gastrointestinal complications of NSAIDs yearly.

There are other, nonpharmacologic ways to reduce inflammation, Dr Raison noted: spirituality, Mediterranean diet, exercise, meditation, and prevention of early-life trauma or neglect.


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