Major depression is one of the most common mental disorders in the United States. An estimated 17.3 million adults had at least one major depressive episode in 2017. The prevalence of major depressive episode was higher among adult females (8.7%) compared to males (5.3%). There was an 18% increase in depression cases between 2005 and 2015.

An estimated 65% of those with depression received combined care by a health professional and medication treatment. Treatment with medication alone was least common (6%). Approximately 35% of adults with major depressive episode did not receive treatment.

According to a pooled analysis, anti-inflammatories, such as aspirin/paracetamol, statins, and antibiotics can safely and effectively control or limit the symptoms of major depression. The effects of these agents are even stronger when added to standard antidepressant treatment.

Although it is thought that inflammation may contribute to the development of major depression, clinical trials have been inconclusive. The agents in this review included non-steroidal anti-inflammatory drugs (NSAIDs), omega-3 fatty acids, cytokine inhibitors, statins, steroids, antibiotics (minocyclines); modafinil (sleep disorder), and N-acetyl cysteine (NAC), which is prescribed to loosen the excess phlegm of cystic fibrosis and COPD and also taken as an antioxidant supplement.

The researchers studied databases to find suitable studies published up to January 2019. They found 30 relevant randomized controlled trials, involving 1,610 people, which reported changes in depression scales.

The pooled data analysis from 26 studies 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 and 79% more effective in eliminating symptoms than placebo, as measured by an average fall in depression scales of 55.

NSAIDs, omega-3 fatty acids, statins, and minocyclines were the most effective at reducing major depressive symptoms compared with placebo. The effects were even greater when one or other of these agents was added to standard antidepressant treatment.

No major side effects were evident, although there were some gut symptoms among those taking statins and NACs. These trials were short term (4-12 weeks), so tracking side effects over a longer period was not possible, which is an important consideration. Still, 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.