Accessibility and safety of antipsychotics in the treatment of Autism Spectrum Disorder in children and adolescents

Abstract

Risperidone and aripiprazole (RiAr) are the only approved drugs by the FDA for the treatment of irritability associated with Autism Spectrum Disorder (ASD) in children and adolescents. The regulatory bodies in Europe (European Medicines Agency) and India (The Central Drugs Standard Control Organization) have not approved the drugs for the indication of ASD. Cultural, economic and regulatory variations may impact the approach towards the treatment of ASD in India and Malta. The objectives of the research are to 1) develop and administer a questionnaire to psychiatrists in India and Malta 2) evaluate and compare the accessibility and affordability of RiAr and 3) detect adverse drug reactions (ADRs) not listed in the approved Summary of Product Characteristics (SmPC) in children and adolescents treated with RiAr for ASD through Eudravigilance. The methodology included 1) a questionnaire, entitled ASD-Q (IND-MT) which was developed, validated (by 10 experts) and disseminated to psychiatrists (N=47) in India (n=31) and Malta (n=16). ASD-Q(IND-MT) consisted of 6 sections and 28 close ended Likert scale questions ranging from 1 (strongly disagree) to 5 (strongly agree) and gathered opinions on the perception of ASD, influence of culturally developed screening tools, Childhood Autism Rating Scale (CARS) in Malta and the Indian Scale of Assessment (ISAA) in India, prescribing behaviour of RiAr and role of pharmacists in managing ASD, 2) a comparison of the price of RiAr against the Monthly Per Capita Expenditure (MPCE) in India and Malta to obtain an indication of the affordability of the treatment, 3) Eudravigilance signal detection and French causality assessment was carried out and ADRs received duringNovember 2001 to September 2017 were extracted in the age group 6-17 years (risperidone) and 5-16 years (aripiprazole). Statistical analysis of the ASD-Q (IND-MT) indicated a significant difference (p<0.05) between the prescribing behaviour of RiAr. A significant difference (p=0.040) was noted between the psychiatrists when asked about the interpretation of the screening tools (ISAA/CARS) score. Thirteen Indian psychiatrists out of 31 and 2 Maltese psychiatrists out of 16 agreed that they prescribe RiAr to patients with mild to moderate autism. Eighteen Indian psychiatrists out of 31 and 14 Maltese psychiatrists out of 16 agreed that they would prescribe antipsychotics to patients who have severe autism. A statistically significant difference (p<0.001) is noted between psychiatrists when asked about the influence of screening tools (ISAA/CARS) on the prescribing behaviour of antipsychotics. The Likert mean score was 4.45±0.506 by Indian psychiatrists and 2.56±1.153 by Maltese psychiatrists indicating higher agreement by the Indian psychiatrists. The Cost analysis of RiAr revealed that RiAr would cost €3.5 and €3.9 in India and €26.7 and €28.8 in Malta monthly. The percentage of MPCE required for one month of treatment with RiAr is 11.30% and 12.60% in India and 3.30% and 3.56% in Malta respectively. Five ADR signals were assessed for risperidone and three signals for aripiprazole. The French causality assessment concluded “uncertain” or “unlikely” relation between the ADR signals and the drugs. Culturally developed screening tools have a different influence on the prescribing behaviour of drugs in India and Malta. The cost of medicines is low in India compared to Malta but the treatment is more affordable in Malta. The SmPC of RiAr includes all the ADRs indicated through the EudraVigilance signal detection in this study.