A Comparison of the Treatment Effects of a Risperidone Solution, an Equal Ratio of DHA/ARA, and a Larger Ratio of Omega-6 PUFA Added to Omega-3 PUFA: An Open-Label Clinical Trial.

We aimed to assess the efficacy, safety, and pharmacokinetics of an oral risperidone solution and two types of supplementations with PUFAs. We assigned 39 participants with mild ASD (mean age ± standard deviation = 14.6 ± 6.0 years) to three treatment groups (each n = 13): RIS-OS; equal doses of 240 mg of omega-3 PUFA docosahexaenoic acid and omega-6 PUFA arachidonic acid (1:1) (aravita); and omega-6 precursor linoleic acid (480 mg) and omega-3 precursor alpha-linolenic acid (120 mg) (4:1) (awake). The primary outcome was the Autism Diagnostic Interview-Revised score. The secondary outcomes were the Social Responsiveness Scale (SRS) and Aberrant Behavior Check scores. The results of the linear mixed-effects model revealed that the RIS-OS group exhibited significant improvement in the SRS subscale scores of social motivation at weeks 8, 12, and 16 compared with the aravita and awake groups, as well as in the SRS subscale score of social mannerisms at weeks 12 and 16 compared with the aravita group. Moreover, the RIS-OS group showed a trend towards significantly lower plasma ceruloplasmin (Cp) levels. Their plasma insulin-like growth factor (IGF) levels were significantly higher at week 8 than in the subsequent weeks. The high Cp and IGF levels may be attributed to reduced neuroinflammation. These findings demonstrate, firstly, that reduced inflammation through increased anti-inflammatory proteins such as Cp and IGF has clinical effects on the motivation-reward system and mannerisms in patients with ASD through the amelioration of dopamine D2, 5-HT2a, and 5-HT2b dysfunction.