COX-2 Inhibitors, Aspirin, and Other Potential Anti-Inflammatory Treatments for Psychiatric Disorders.

Norbert Müller

doi:10.3389/fpsyt.2019.00375

Abstract

Inflammatory processes associated with persistent (chronic) infection have long been discussed as etiological factors in psychiatric disorders. Studies have found that people with major depression have higher levels of pro-inflammatory cytokines, for example, IL-1, IL-6, and tumor necrosis factor-alpha, and C-reactive protein. In schizophrenia, many reports have described raised levels of cytokines, for example, IL-6; and meta-analyses have confirmed these findings. Microglia cells are important in inflammatory processes, and positron emission tomography studies have shown microglia activation in both depression and schizophrenia.As a consequence of the above findings, immunomodulation is widely discussed as a potential treatment approach in both major depression and schizophrenia. The COX-2 inhibitor celecoxib was found to have a significant positive effect on major depression, not only in single studies but also in meta-analyses. Celecoxib has also been studied in schizophrenia and has shown efficacy, in particular, in early disease stages. The mixed COX inhibitor aspirin (acetylsalicylic acid) seems to have both protective and therapeutic effects on schizophrenia.This paper discusses the hypothesized role of inflammation in major depression and schizophrenia, including markers of inflammation; pertinent studies on celecoxib and aspirin; and additional immunomodulatory therapeutic strategies.

Highlights

Studies in animal models have provided evidence that both early infection and immune activation can affect several neurodevelopmental processes, including serotonergic [1] and dopaminergic and glutamatergic neurotransmission [2, 3]
If people were hospitalized for infection, the risk increased by 62% [incidence rate ratio (IRR) 1.62]; and if they visited the hospital because of an autoimmune disease, it increased by 45% (IRR 1.45)
Significant therapeutic effects have been shown for the COX-2 inhibitor celecoxib in major depression (MD) and early-stage schizophrenia, and protective and therapeutic effects have been shown for the mixed COX-1 and COX-2 inhibitor ASA in schizophrenia

Summary

INTRODUCTION

Studies in animal models have provided evidence that both early infection and immune activation can affect several neurodevelopmental processes, including serotonergic [1] and dopaminergic and glutamatergic neurotransmission [2, 3]. If the study had assessed all kinds of infections— those for which people visited a hospital—the risk of developing a mood disorder might have been even higher [10] Another Danish population-based register study evaluated whether the use of anti-inflammatory agents, including aspirin (acetylsalicylic acid [ASA], an inhibitor of both COX-1 and COX-2), is associated with a lower rate of depression [11]. The findings of another meta-analysis on inflammationrelated therapeutic approaches in MD are of great interest [21] This analysis evaluated data from 14 studies (10 on NSAIDs, n = 4,258; 4 on cytokine inhibitors, n = 2,004) and found that the anti-inflammatory treatments had positive effects compared with placebo [standardized mean difference (SMD), −0.34; 95% confidence interval (CI), −0.57 to −0.11; I2 = 90%], both in depression (SMD, −0.54; 95% CI, −1.08 to −0.01; I2 = 68%) and in depressive symptoms (SMD, −0.27; 95% CI, −0.53 to −0.01; I2 = 68%).

Study design

Findings

CONCLUSION