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Anti-inflammatories effective and safe with major depression

Anti-inflammatory medicines were better than placebo and also enhanced the effects of standard antidepressant treatment, to safely curb the symptoms of major depression, found a meta-analysis of 26 randomised controlled trials.

Anti-inflammatory agents, such as aspirin/paracetamol, statins, and antibiotics, can safely and effectively curb the symptoms of major depression, finds a pooled analysis of the available evidence. And the effects are even stronger when these agents are added on to standard antidepressant treatment, the results show.

Around a third of people who are clinically depressed don't respond well to current drug and talking therapies, and drug side effects are relatively common.

An emerging body of evidence suggests that inflammation contributes to the development of major depression, but the results of clinical trials using various anti-inflammatory agents to treat the condition have proved inconclusive.

The researchers at the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, therefore set out to review the available evidence and pool the data to see if anti-inflammatory agents work better than dummy (placebo) treatment either alone or when used as add-on therapy to standard antidepressant treatment.

Anti-inflammatory agents included: non-steroidal anti-inflammatory drugs (NSAIDs); omega 3 fatty acids; drugs that curb production of inflammatory chemicals (cytokine inhibitors); statins; steroids; antibiotics (minocyclines); a drug used to treat sleep disorders (modafinil); and N-acetyl cysteine, known as NAC, and used to loosen the excess phlegm of cystic fibrosis and COPD and also taken as an antioxidant supplement.

The researchers trawled research databases to find suitable studies published up to January 2019. They found 30 relevant randomised controlled trials, involving 1610 people, which reported changes in depression scales. They pooled the data from 26 of these studies.

The pooled data analysis suggested that anti-inflammatory agents were better than placebo and enhanced the effects of standard antidepressant treatment. These agents were 52% more effective in reducing symptom severity, overall, and 79% more effective in eliminating symptoms than placebo, as measured by an average fall in depression scales of 55.
More detailed analysis indicated that NSAIDs, omega 3 fatty acids, statins, and minocyclines were the most effective at reducing major depressive symptoms compared with placebo.

And the effects were even greater when one or other of these agents was added to standard antidepressant treatment.

But anti-inflammatory agents didn't seem to improve quality of life, although this might have been because of the small number of studies which looked at this aspect, say the researchers.

No major side effects were evident, although there were some gut symptoms among those taking statins and NACs, and the trials lasted only 4 to 12 weeks, so it wasn't possible to track side effects over the longer term.

The researchers also point out that not all studies tracked changes in depression scores over the entire study period. The depression scales used in the studies differed, and those involving statins and minocyclines included only small numbers of patients.

Nevertheless, they conclude: The results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with major depressive disorder and are reasonably safe."

The Daily Telegraph reports that commenting on the research, Professor Ed Bullmore, head of department of psychiatry, at the University of Cambridge, said: "This should encourage further consideration of ways in which we could use a range of anti-inflammatory interventions to help people with depression, perhaps especially people who are already taking a conventional antidepressant drug with limited benefit.”

Figures also show that around 30 per cent of people suffering from inflammatory diseases such as rheumatoid arthritis are depressed – more than four times higher than the normal population.

Likewise people who are depressed after a heart attack are much more likely to suffer a second one, while the lifespan for people with cancer is hugely reduced for people with mental illness.

However, the report quotes Professor David Curtis, retired consultant psychiatrist and honorary professor at University College London and Queen Mary University London, said it may be more dangerous to prescribe anti-inflammatories long term. “Given that one would need to take treatment for several months, I don’t see that it makes sense to advocate treating depressed patients with potentially dangerous medications with at best weak effects rather than just use antidepressants, which are actually safe and effective.”

Abstract
Objectives: To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.
Methods: We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.
Results: Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.
Conclusions: Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Authors
Shuang Bai, Wenliang Guo, Yangyang Feng, Hong Deng, Gaigai Li, Hao Nie, Guangyu Guo, Haihan Yu, Yang Ma, Jiahui Wang, Shiling Chen, Jie Jing, Jingfei Yang, Yingxin Tang, Zhouping Tang

[link url="https://www.news-medical.net/news/20191029/Anti-inflammatory-agents-can-safely-effectively-reduce-symptoms-of-major-depression.aspx"]News-Medical report[/link]

[link url="https://jnnp.bmj.com/content/early/2019/08/29/jnnp-2019-320912"]Journal of Neurology, Neurosurgery & Psychiatry abstract[/link]

[link url="https://www.telegraph.co.uk/science/2019/10/28/anti-inflammatory-drugs-like-ibuprofen-aspirin-can-battle-major/"]The Daily Telegraph report[/link]

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