The inflammatory hypothesis of schizophrenia is not new, but recently it has regained interest because more data suggest a role of the immune system in the pathogenesis of schizophrenia. If increased inflammation of the brain contributes to the symptoms of schizophrenia, reduction of the inflammatory status could improve the clinical picture. Lately, several trials have been conducted investigating the potential of anti-inflammatory agents to improve symptoms of schizophrenia. This study provides an update regarding the efficacy of anti-inflammatory agents on schizophrenic symptoms in clinical studies performed so far. Methods: An electronic search was performed using PubMed, Embase, the National Institutes of Health web site http://www.clinicaltrials.gov, Cochrane Schizophrenia Group entries in PsiTri, and the Cochrane Database of Systematic Reviews. Only randomized, double-blind, placebo-controlled studies that investigated clinical outcome were included. Results: Our search yielded 26 double-blind randomized controlled trials that provided information on the efficacy on symptom severity of the following components: aspirin, celecoxib, davunetide, fatty acids such as eicosapentaenoic acids and docosahexaenoic acids, estrogens, minocycline, and N-acetylcysteine (NAC). Of these components, aspirin (mean weighted effect size [ES]: 0.3, n = 270, 95% CI: 0.06-0.537, I2 = 0), estrogens (ES: 0.51, n = 262, 95% CI: 0.043-0.972, I2 = 69%), and NAC (ES: 0.45, n = 140, 95% CI: 0.112-0.779) showed significant effects. Celecoxib, minocycline, davunetide, and fatty acids showed no significant effect. Conclusion: The results of aspirin addition to antipsychotic treatment seem promising, as does the addition of NAC and estrogens. These 3 agents are all very broadly active substances, and it has to be investigated if the beneficial effects on symptom severity are indeed mediated by their anti-inflammatory aspects.
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