Adjunctive Use of Nonsteroidal Anti-inflammatory Drugs for Schizophrenia: A Meta-analytic Investigation of Randomized Controlled Trials

Abstract

These results indicate that adjunctive NSAIDs for schizophrenia may not benefit patients treated with first-line antipsychotics judged by PANSS total score change. NSAIDs may have benefits for positive symptoms, but the effect was minimal/small. However, due to a limited database, further controlled studies are needed, especially in first-episode patients.

What role does inflammation play in schizophrenia?

“…A recent study also demonstrated a beneficial effect of acetylsalicylic acid in schizophrenic spectrum disorders [42]. A meta-analysis of the clinical effects of nonsteroidal anti-inflammatory drugs in schizophrenia revealed significant effects on schizophrenic total, positive and negative symptoms [43], while another meta-analysis found a significant benefit only in schizophrenia patients with a short duration of disease or in first manifestation schizophrenia [44].…”

Nonsteroidal Anti-inflammatory Drugs and 5-HT3Serotonin Receptor Antagonists as Innovative Antipsychotic Augmentation Treatments for Schizophrenia

“…Nitta et al 14 therefore examined the subject in a systematic review and metaanalysis. The authors searched electronic databases, clinical trial registries, reference lists, and other sources and identified 8 relevant placebo-controlled RCTs (pooled N = 774), including 3 that had not been published.…”

Anti-inflammatory strategies in the treatment of schizophrenia

“…Another recent meta-analysis [6] that pooled the data from the two drugs and examined different domains of benefit found no significant benefit with anti-inflammatory drug augmentation for attenuation of Positive and Negative Syndrome Scale (PANSS) total scores or PANNS-negative scores; whereas there was significant decrease in PANSS-positive scores, the benefit was almost negligibly small (Hedges' g, 0.19). Because of high heterogeneity, secondary analyses of PANSS total scores were conducted; these found a small advantage for aspirin but not celecoxib; for antiinflammatory augmentation in RCTs of in-patients but not those that included out-patients; and for anti-inflammatory augmentation in RCTs that included first-episode patients but not in RCTs of only chronic patients (significant Hedges' g range, 0.29-0.44).…”

“…Aspirin resulted in significantly improved outcomes in metaanalyses [5,6]. However, one [7] of the two aspirin RCTs has not yet been published although the abstract appeared in print in 2012.…”

“…As already stated, in meta-analysis, celecoxib did not outperform placebo [5,6]. Two of these RCTs were completed more than a decade ago; both failed to find an advantage for celecoxib and were never published in full [11,12].…”