Anti-inflammatory agents can effectively and safely curb major depressive symptoms
Effects even stronger when added to antidepressant treatment, pooled data analysis shows
October 28, 2019
Science Daily/BMJ
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, published online in the Journal of Neurology Neurosurgery & Psychiatry.
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 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."
https://www.sciencedaily.com/releases/2019/10/191028213923.htm
Stress in early life could make people more likely to develop depression
May 8, 2019
Science Daily/University of Bristol
New research by the University of Bristol has found that early life adversity could make an individual more at risk of developing negative thinking, which could lead to major depressive disorder (MDD). The findings provide biological and psychological evidence to support work first proposed in the 1960s.
The study, published in Neuropsychopharmacology and funded by the MRC and BBSRC, using a rodent model of early life adversity, has shown that offspring are much more sensitive to negative biases in their cognition when treated with the stress hormone, corticosterone.
The research has shown a dose of corticosterone had no effect in normal rats but caused a negative bias in the early life adversity animals. The study also found that the early life adversity rats were less likely to anticipate positive events and failed to properly learn about reward value. These impairments in reward-related cognition are particularly interesting as one of the main features of depression is a loss of interest in previously enjoyable activities.
The findings support the idea that those at risk of developing mood disorders may have impairments in the way they learn about and use their memories about how rewarding an experience has been to then guide and motivate them to repeat the activity. The researchers suggest that these neuropsychological effects might explain why early life adversity can make people more likely to develop depression.
Emma Robinson, Professor of Psychopharmacology, School of Physiology, Pharmacology & Neuroscience and lead author on the paper, said: "This study supports a wider body of literature which suggests that depression may develop from an interesting yet complex interaction between biological and psychological processes. As we start to understand these better we hope that the knowledge we generate can be used to better guide current and future treatments.
"Our larger body of work suggests that the effectiveness of current antidepressant treatments might be linked to how much a person is able to re-engage with their environment and their level of social support.
"The findings also add further evidence to support the validity of this relatively new area of research into mood disorders, particularly studies using animals to understand the neurobiology of affective biases and how they contribute to normal and pathological behaviour."
Studies in patients have shown that depression is linked to changes in how the person processes information particularly emotional information. People with depression have a negative view of the world which can be measured by looking at how they process information such as emotional faces and words. However, whether this causes the illness or are a consequence is not known.
The researchers developed a method to use in rodents where similar neuropsychological processes were measured. One of the tasks, the affective bias test, looked at how simple associations between a specific cue, a bowl with a specific digging substrate in it, and a reward, a food pellet, could be biased by the animal's affective state when they learn about it.
When animals learn the association in a negative affective state they remember it in a more pessimistic way whilst memories formed in a positive affective state are remembered in a more positive way. The biases the study was able to measure in rodents correlated exactly with how these same treatments affect peoples' mood in the long-term, something which no other animal test in psychiatry has been able to achieve.
The next step in the research will be to understand how these processes and the deficits seen in the animals respond to current antidepressant treatments including the recently licensed, rapid onset antidepressant ketamine. The researchers already have some evidence about how ketamine interacts with these neuropsychological processes and this latest work will help them bring these findings together with an important disease model and risk factor for depression.
https://www.sciencedaily.com/releases/2019/05/190508113326.htm