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Review
. 2023 Mar;37(3):215-229.
doi: 10.1007/s40263-023-00993-x. Epub 2023 Mar 13.

Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials

Gara Arteaga-Henríquez  1   2   3   4 , Laura Gisbert  1   2   3   5 , Josep Antoni Ramos-Quiroga  6   7   8   9
Affiliations
Review

Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials

Gara Arteaga-Henríquez et al. CNS Drugs. 2023 Mar.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a so far poorly understood underlying pathogenesis, and few effective therapies for core symptoms. Accumulating evidence supports an association between ASD and immune/inflammatory processes, arising as a possible pathway for new drug intervention. However, current literature on the efficacy of immunoregulatory/anti-inflammatory interventions on ASD symptoms is still limited. The aim of this narrative review was to summarize and discuss the latest evidence on the use of immunoregulatory and/or anti-inflammatory agents for the management of this condition. During the last 10 years, several randomized, placebo-controlled trials on the effectiveness of (add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, N-acetylcysteine (NAC), sulforaphane (SFN), and/or omega-3 fatty acids have been performed. Overall, a beneficial effect of prednisolone, pregnenolone, celecoxib, and/or omega-3 fatty acids on several core symptoms, such as stereotyped behavior, was found. (Add-on) treatment with prednisolone, pregnenolone, celecoxib, minocycline, NAC, SFN, and/or omega-3 fatty acids was also associated with a significantly higher improvement in other symptoms, such as irritability, hyperactivity, and/or lethargy when compared with placebo. The mechanisms by which these agents exert their action and improve symptoms of ASD are not fully understood. Interestingly, studies have suggested that all these agents may suppress microglial/monocyte proinflammatory activation and also restore several immune cell imbalances (e.g., T regulatory/T helper-17 cell imbalances), decreasing the levels of proinflammatory cytokines, such as interleukin (IL)-6 and/or IL-17A, both in the blood and in the brain of individuals with ASD. Although encouraging, the performance of larger randomized placebo-controlled trials, including more homogeneous populations, dosages, and longer periods of follow-up, are urgently needed in order to confirm the findings and to provide stronger evidence.

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Conflict of interest statement

All authors have no financial relationships to disclose relevant to this article. Josep Antoni Ramos-Quiroga was on the speakers’ bureau and/or acted as a consultant for Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years, and also received travel awards (air tickets + hotel) from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice for taking part in psychiatric meetings. The Department of Psychiatry chaired by Josep Antoni-Ramos-Quiroga received unrestricted educational and research support from Janssen-Cilag, Shire, Oryzon, Roche, Psious, and Rubió in the last 3 years.

Figures

Fig. 1
Fig. 1
Immune system abnormalities in ASD
See this image and copyright information in PMC

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