Anti-inflammatories may have anti-depressant properties

By David Douglas

NEW YORK (Reuters Health) - Pooled data suggest that anti-inflammatory medication may have a positive effect on depression, according to an international group of researchers.

"Thus, our results support a connection between physical and mental disorders," Dr. Ole Köhler from Aarhus University Hospital, Risskov, Denmark, told Reuters Health by email.

"Some studies," he added, "have emphasized the possibility that a simple blood test, indicating the presence of inflammation in the body, might help in identifying those patients who could benefit of anti-inflammatory treatment. These are very promising results for clinical practice in psychiatry, where no standard laboratory markers exist supporting the right treatment choice."

Dr. Köhler and colleagues examined data from 14 trials with more than 6,000 participants. Ten of the trials investigated use of NSAIDs and included 4,258 participants, while the remaining studied cytokine inhibitors.

The antidepressant effects of cytokine inhibitors were no better than for placebo, the researchers report in JAMA Psychiatry, online October 15.

But, overall, there was a suggestion that anti-inflammatory treatment reduced depressive symptoms more than placebo, giving a standard mean difference of -0.34. This was the case in studies including both patients with depression (-0.54) and depressive symptoms (-0.27).

Subanalyses pointed to the selective COX-2 inhibitor celecoxib as particularly effective (SMD, -0.29). This was true of both remission (odds ratio, 7.89) and response (OR, 6.59).

In the six studies reporting adverse events, there was no evidence of an increase in gastrointestinal or cardiovascular events after six week of treatment. This was also the case for infections after 12 weeks of cytokine inhibitor treatment.

"Specific agents, particularly celecoxib, showed promising results and should therefore be investigated in high-quality randomized clinical trials," the researchers conclude.

Dr. Köhler added that more thorough investigation is need to determine which patients might benefit from anti-inflammatory treatment, how long treatment should last and which doses should be used. "Furthermore," he said, "the benefit should always be balanced against potential side effects."

Dr. Iris Sommer, who was conducted similar research, said the results were similar "to my meta-analysis which looked at anti-inflammatory agents for schizophrenia."

"In several psychiatric disorders (in particular schizophrenia, bipolar disorder and unipolar depression) the immune system plays an important role in the disease process, probably from the early stages onward," Dr. Sommer of University Medical Centre Utrecht in the Netherlands told Reuters Health by email. "We see that in schizophrenia genes that are related to the immune system are also associated with this disease. For depression this relation is less clear."

"This review," she continued, "shows that depressive symptoms reduce after treatment for a somatic disorder with an anti-inflammatory agents. Of course this could suggest that decreasing CNS inflammation may alleviate depressive symptoms, but this cannot be directly deduced from the data. Most anti-inflammatory agents (especially celecoxib) are also pain killers and the relationship between chronic pain and depression is strong. Thus, another interpretation of the data is that pain relief improves depressive symptoms, which is no more than common sense."

Another point, Dr. Sommer added, "is that the authors state that celecoxib is not associated with increased side-effects in these groups. Fact is that they did not observe a significant difference in adverse events in their data, but many anti-inflammatory drugs are well known to induce rather severe side-effects in high proportions of patients."

Pfizer conducted five of the studies included in the analysis, but had no role in the new study.

SOURCE: http://bit.ly/1pAxEqH

JAMA Psychiatry 2014.

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