Cilostazol as adjunctive therapy in treatment of children with autism spectrum disorders: a double-blind and placebo-controlled randomized trial

Abstract

We aimed to evaluate cilostazol therapeutic effects on aberrant behaviors of autism spectrum disorder (ASD) children and its safety profile in a double-blind, randomized clinical trial. Sixty-six children with confirmed ASD were allocated to receive either daily 50-mg cilostazol (increased to 100 mg/day after 2 weeks) or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and a checklist of probable adverse effects were used to assess the behavioral outcomes and safety profile at weeks 0, 5, and 10 of the study. Sixty-one participants, with comparable baseline characteristics, completed the trial. Unlike other ABC-C subscales, repeated-measures analysis showed significant effect for time × treatment interaction in the hyperactivity subscale (P = 0.047; partial eta squared = 0.06). We used the median value for the baseline score hyperactivity subscale [median (interquartile range) = 31 (24-37)] to stratify participants to higher hyperactivity and lower hyperactivity subgroups and found that only participants with higher hyperactivity benefit from cilostazol adjunctive therapy (P = 0.028; partial eta squared = 0.14). Cilostazol could be considered as a safe agent with beneficial effects on hyperactivity in children with ASD and higher levels of hyperactivity.

The anti-platelet drug cilostazol enhances heart rate and interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish

“…Although it is generally uncertain whether cilostazol is safe and effective for use in children, a clinical trial testing the effects of cilostazol for the treatment of juvenile Raynaud’s Phenomenon, a blood vessel disorder in children, has been completed with no significant beneficial effects discovered [ 79 ]. Also, cilostazol has been tested effective in a rat model of prenatal valproic acid-induced autism spectrum disorder [ 80 ] and hence proposed as an adjunctive therapy for the children with autism spectrum disorder [ 81 ]. However, our study suggests potential adverse endocrine effects of cilostazol for use during developmental stages, which need to be carefully assessed.…”

The anti-platelet drug cilostazol enhances interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish

“…Although it is generally uncertain whether cilostazol is safe and effective for use in children, a clinical trial testing the effects of cilostazol for the treatment of juvenile Raynaud's Phenomenon, a blood vessel disorder in children, has been completed with no significant beneficial effects discovered [67]. On the other hand, cilostazol has been tested effective in a rat model of prenatal valproic acid-induced autism spectrum disorder [68] and hence proposed as an adjunctive therapy for the children with autism spectrum disorder [69]. However, our study suggests potential adverse endocrine effects of cilostazol for use in developing young patients, which need to be carefully assessed.…”

The challenge of managing difficult to treat psychiatric conditions

“…Cilostazol is a reversible, selective phosphodiesterase III inhibitor used for patients with ischemic vascular diseases, as it shows antiplatelet aggregation effects; however, it also modulates long-term memory, synaptic plasticity, and maintenance of neuronal health through multiple intracellular mechanisms (Ebrahimi et al , 2022). Its mechanism of action is, therefore, interesting for ASD treatment.…”

“…Therefore, further options are needed in clinical practice. In this issue, Ebrahimi et al (2022) report the possible benefit of an innovative treatment, cilostazol, as an adjunctive treatment in children with ASD.…”