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Anti-Inflammatory Treatment: Effect on Depression and Adverse Effects.

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Anti-Inflammatory Treatment: Effect on Depression and Adverse Effects.

Post  Admin on Wed Dec 10, 2014 11:46 pm


The current edition of JAMA psychiatry published this systematic review and meta-analysis of randomized clinical trials done by Ole Kohler and colleagues. According to author, this is the largest study on anti-inflammatory treatment for depressive symptoms.

Background:
Recently studies have investigated the role of anti-inflammatory medications (NSAIDS and Cytokine Inhibitors) in improvement of antidepressant response.

Mechanism:
- NSAIDS inhibits COX-2, which inhibits the production of pro inflammatory cytokines.
- Cytokine inhibitors acts directly on these pro inflammatory cytokines.

Method:
Only randomized placebo-controlled trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles.
Anti-inflammatory treatment is defined as NASIDs, COX-2 inhibitors, pro-inflammatory cytokine inhibitors and Minocycline hydrochloride.

Results & Discussion:
- 14 trials (6262 participants) included= 10 trials of NSAIDs (nā€‰=ā€‰4258) and 4 trials of cytokine inhibitors (nā€‰=ā€‰2004).
- The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms compared with placebo.
- This effect was observed in studies including patients with depression and depressive symptoms
- NSAIDS were associated with better antidepressant effects in general, whereas a statistical trend favored cytokine inhibitors.
- Subanalyses emphasized the antidepressant properties of the selective COX-2 inhibitor celecoxib on remission and response.
- NSADIS are known to increase the risk of GI and CV adverse effects; and Cytokine inhibitors are known to increase the risk for infections. Among the 6 studies reporting on adverse effects, no evidence found of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo.
- All trials were associated with a high risk of bias owing to potentially compromised internal validity.

* All randomized studies emphasized the adjunctive antidepressant effects of Calecoxib within first 6-8 weeks of antidepressant treatment- this is suggested to be most pronounced in patients with increased pro-inflammatory markers.

* Note: Not all studies reported adverse effects, thereby complicating the assessment. Also the treatment lasted only 6-12 weeks, which is too short to detect relevant adverse effects. SO RESULTS SHOULD BE INTERPRETED CAUTIOUSLY.

Other agents with possible anti-inflammatory potential (speculative ?):
- Aspirin: recent reviews emphasize favorable benefit to risk ration and better antidepressant effects (compared to selective COX-2 inhibitors)- but no randomize control trial published.
- Statins
- Minocycline- crosses blood brain barrier- but no randomize control trial published.
- Pioglitazone
- Modafinil
- Polyunsaturated fatty acids

Conclusions:
- This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression.
- Identification of subgroups that could benefit from such treatment might be warranted.


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