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Riluzole as an Adjunctive Therapy to Risperidone for the Treatment of Irritability in Children with Autistic Disorder: A Double-Blind, Placebo-Controlled, Randomized Trial

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Abstract

Background

A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders.

Objective

The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications.

Study Design

This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial.

Participants

The study enrolled male and female outpatients aged 5–12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy.

Interventions

Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks.

Outcome

Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups.

Results

Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech subscale (P = 0.20) than patients in the placebo group. Eleven patients in the riluzole group and five patients in the placebo group were classified as responders based on their CGI-I scores [χ2(1) = 3.750, P = 0.05]. Children in the riluzole group experienced significantly more increases in their appetite and bodyweight than children in the placebo group by the end of the study.

Conclusion

Riluzole add-on therapy shows several therapeutic outcomes, particularly for improving irritability, in children with autism. However, its add-on to risperidone also results in significantly increased appetite and weight gain.

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Acknowledgments

This study was Dr. Effat Mohammadi’s postgraduate thesis toward the Iranian Board of Psychiatry. The study was supported by a grant from Tehran University of Medical Sciences to Prof. Shahin Akhondzadeh (grant number 14037). The funding organization had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript and the decision to submit the paper for publication.

Conflict of Interest Statement

Drs. Ghaleiha, E. Mohammadi, M.-R. Mohammadi, Farokhnia, Modabbernia, Yekehtaz, Ashrafi, Hassanzadeh and Akhondzadeh have no conflicts of interest associated with this manuscript, and there was no source of extra-institutional commercial funding.

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Correspondence to Shahin Akhondzadeh.

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Clinical Trial Registration: Iranian Registry of Clinical Trials (http://www.irct.ir), IRCT201107281556N27.

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Ghaleiha, A., Mohammadi, E., Mohammadi, MR. et al. Riluzole as an Adjunctive Therapy to Risperidone for the Treatment of Irritability in Children with Autistic Disorder: A Double-Blind, Placebo-Controlled, Randomized Trial. Pediatr Drugs 15, 505–514 (2013). https://doi.org/10.1007/s40272-013-0036-2

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