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.
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.