Summary: Anti-inflammatory medications, including drugs commonly used for arthritis, show beneficial effects on depressive symptoms in people with major depressive disorder (MDD).
Source: Aarhus University
Depression is among the most serious global mental health conditions, according to the World Health Organization, and researchers are actively seeking better treatment options.
In the largest meta-analysis to date, researchers from iPSYCH and collaborating institutions have found that medications that reduce inflammation can help alleviate depressive symptoms. The analysis pooled data from dozens of randomized clinical trials and suggests that anti-inflammatory drugs may enhance antidepressant response for some patients.
“Our study indicates that adding certain anti-inflammatory medications to standard antidepressant therapy can provide an additional benefit for patients with depression,” explains Ole Köhler-Forsberg, MD, PhD, from Aarhus University and Aarhus University Hospital, Psychiatry. “We also observed an antidepressant effect when anti-inflammatory treatments were compared with placebo in patients who had a physical illness together with depressive symptoms.”
Medications showing antidepressant effects
The meta-analysis reviewed 36 randomized controlled trials involving 9,422 participants who either had major depressive disorder or clinically relevant depressive symptoms. Results appear in Acta Psychiatrica Scandinavica.
Investigators evaluated a range of anti-inflammatory agents beyond classic arthritis medications. These included nonsteroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, glucocorticoids, the antibiotic minocycline, adrenocortical hormone analogues, statins, and insulin-sensitizing agents such as pioglitazone. Across the reviewed trials, several of these drug classes produced measurable antidepressant effects.
“This evidence strengthens the prospect of more personalized treatment approaches for depression,” says Köhler-Forsberg. “However, any potential benefits must be balanced against known side effects of anti-inflammatory drugs. We still need to determine which patients are most likely to benefit, the optimal dosing, and the recommended duration of treatment. Patients should consult their clinician before adding any new medication.”
He adds that a core challenge in treating depression is the heterogeneity of the condition: the underlying causes vary between individuals, and this variation likely influences treatment response.
Some studies suggest that blood biomarkers of systemic inflammation could guide treatment selection. Elevated inflammatory markers might identify patients who respond better to anti-inflammatory adjuncts, while low-inflammatory profiles may predict limited benefit. These findings are preliminary and require further confirmation before they can be translated into routine clinical practice.
Several therapeutic options are promising
Michael Eriksen Benros, MD, PhD, research director at the Mental Health Centre Copenhagen, highlights the clinical importance of the findings: “We observed medium-to-large effects for several anti-inflammatory treatments on depressive symptoms. These results are noteworthy because the pooled evidence includes nearly 10,000 participants in placebo-controlled trials.”
Benros emphasizes that the benefits were seen both when anti-inflammatory agents were used alone and when they were added to existing antidepressant regimens.
Despite these encouraging results, many trials included in the meta-analysis measured depressive symptoms as a secondary outcome rather than the primary objective. The authors call for larger, well-designed randomized trials that focus specifically on depression as the primary endpoint. Those studies should have adequate follow-up, carefully evaluate dosing and treatment duration, and identify patient subgroups most likely to benefit from anti-inflammatory strategies.
“Understanding the interaction between the immune system and mood regulation could open up new avenues for treatment,” Benros says. “In the future, anti-inflammatory therapies guided by reliable biomarkers might expand our options for people with depression.”
Study background and methodology
A meta-analysis combines data from multiple independent studies to produce an overall estimate of effect. This analysis included randomized clinical trials published up to January 1, 2018, that tested pharmacological anti-inflammatory interventions in adults with major depressive disorder or depressive symptoms. Outcomes assessed included standardized depression scores, rates of response and remission, and adverse events.
Among the 36 randomized controlled trials identified, investigators reviewed studies of NSAIDs, cytokine inhibitors, statins, minocycline, pioglitazone, and glucocorticoids. Across trials, anti-inflammatory agents improved depressive symptom scores both as add-on treatment for MDD and as monotherapy in participants with depressive symptoms. The analysis also noted trends toward increased infection risk and highlighted a generally high risk of bias across many included studies, underlining the need for more rigorous trials.
Publication and funding
The research was conducted by teams at Aarhus University and the Mental Health Centre Copenhagen, Copenhagen University Hospital, and was funded in part by the Lundbeck Foundation via iPSYCH. Full results were published under the title: “Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials” in Acta Psychiatrica Scandinavica.
Original research (open access)
“Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials” by O. Köhler-Forsberg et al., Acta Psychiatrica Scandinavica.