April 11, 2019
2 min read

Anti-inflammatory agents improve antidepressant effects

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Image of Ole Kohler-Forsberg
Ole Köhler-Forsberg

Certain anti-inflammatory drugs improved antidepressant treatment effects and depression symptoms without increasing risk for adverse events, according to findings from a systematic review and meta-analysis.

Evidence has shown that NSAIDs and cytokine inhibitors appear to have beneficial antidepressant treatment response, both as add-on therapy in patients with major depressive disorder and as monotherapy in patients with depressive symptoms, Ole Köhler-Forsberg, MD, from the psychosis research unit at Aarhus University Hospital, Denmark, and colleagues wrote.

“However, several of these studies only investigated specific agents, did not assess the risk for side-effects, only included patients with MDD while excluding patients with a somatic disease and depressive symptoms or failed to perform a thorough bias assessment,” they wrote.

Researchers conducted a systematic review to identify randomized clinical trials (RCTs) with anti-inflammatory drugs measuring antidepressant effects and adverse effects of pharmacological anti-inflammatory intervention in adults with MDD or depressive symptoms. They examined patient depression scores after treatment, remission, response and adverse effects.

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In the 36 trials included in the analyses, those studying add-on therapy lasted 6 to 12 weeks and those studying monotherapy lasted from 6 weeks up to 4 years. Most trials studied NSAIDs (n = 4,214), cytokine inhibitors (n = 3,345) and statins (n = 1,576).

Meta-analysis revealed that anti-inflammatory agents outperformed placebo in improving depressive symptoms as an add-on treatment in patients with major depression (standardized mean difference [SMD] = –0.64; 95% CI, –0.88 to –0.4; I2 = 51%; n = 597) and as monotherapy (SMD = –0.41; 95% CI, –0.6 to –0.22; I2 = 93%, n = 8,825). Adjunctive anti-inflammatory agents also improved response (RR = 1.76; 95% CI, 1.44-2.16; I2 = 16%; n = 341) and remission (RR = 2.14; 95% CI, 1.03-4.48; I2 = 57%; n = 270).

The specific anti-inflammatory drugs that showed superior antidepressant treatment effects to placebo were:

  • NSAIDs (SMD = –0.4; 95% CI, –0.62 to –0.18; I2= 82%);
  • cytokine inhibitors (SMD = –0.56; 95% CI, –0.93 to –0.19; I2 = 95%);
  • statins (SMD = –0.26; 95% CI, –0.48 to –0.04; I2 = 65%);
  • glucocorticoids (SMD = –0.9; 95% CI, –1.44 to –0.36; I2 = 0%); and
  • minocycline (SMD = –0.87; 95% CI, –1.45 to –0.29; I2 = 63%).

The antidepressant effect for pioglitazone was not significant, according to the researchers.

In the trials reporting on adverse effects, researchers found no increased risks for gastrointestinal symptoms, pain/muscle aching or cardiovascular events among patients on anti-inflammatory agents compared with those on placebo. However, there was an increased risk for infections (OR = 1.14; 95%, CI = 0.99-1.31), according to the results.

"This definitely bolsters our chances of being able to provide personalized treatment for individual patients in the longer term,” Köhler-Forsberg said in a press release. “Of course, we always have to weigh the effects against the potential side-effects of the anti-inflammatory drugs. We still need to clarify which patients will benefit from the medicine and the size of the doses they will require.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.