Pura Ballester1,2, María José Martínez3,4, María-Del-Mar Inda1, Auxiliadora Javaloyes5, Amanda L Richdale6, Javier Muriel1, César Belda7, Natalia Toral8, Domingo Morales9, Eduardo Fernández10, Ana M Peiró1,11. 1. Neuropharmacology on Pain (NED), Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. 2. Department of Clinical Pharmacology, Organic Chemistry and Paediatrics, Miguel Hernández University of Elche, Elche, Spain. 3. Chronobiology Lab, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, Murcia Spain. 4. Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain. 5. Education Centre for Children and Adolescents with Autism, Mental Health Problems and Behavioural Disorders (EDUCATEA), Alicante, Spain. 6. Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia. 7. Infanta Leonor Autism Centre, Alicante, Spain. 8. San Rafael Resources Centre, Santa Faz, Spain. 9. Operations Research Centre, Miguel Hernández University of Elche, Elche, Spain. 10. Bioengineering Institute, Miguel Hernández University of Elche, Elche, Spain. 11. Clinical Pharmacology Department, Department of Health of Alicante, Alicante General Hospital, Alicante, Spain.
Abstract
PURPOSE: Intellectual disability (ID) and autism spectrum disorder (ASD) are common, co-occurring developmental disorders and are frequently associated with sleep problems. This study aimed to assess the effectiveness and tolerability of agomelatine as a pharmacotherapy for sleep problems in ASD adults with ID. METHOD: A randomised, crossover, triple-blind, placebo-controlled clinical trial, with two three-month periods of treatment starting with either agomelatine or placebo and a washout period of two weeks. Ambulatory circadian monitoring (24 hours/7 days) evaluated total sleep time (TST) as the primary outcome variable. RESULTS: Participants (N=23; 35±12 years old; 83% male) had a median of three (interquartile range (IQR) 1-4) co-morbidities and were taking a median of five (IQR 2-7) prescribed drugs. Before agomelatine or placebo treatment, all subjects presented with insomnia symptoms, including sleep latency (100% abnormal, 55±23 minutes) or TST (55% abnormal, 449±177 minutes), and 66% had circadian rhythm sleep-wake abnormalities with rhythm phase advancements according to the M5 sleep phase marker values. During the three-month agomelatine treatment, night TST significantly increased by a mean of 83 minutes (16% abnormal, 532±121 minutes), together with a phase correction (M5 1:45±2:28 hours vs. 3:15±2:20 hours), improving sleep stability in wrist temperature rhythm (0.43±0.29 vs. 0.52±0.18 AU). Adverse events were mild and transient. CONCLUSIONS: Agomelatine was effective and well tolerated for treating insomnia and circadian rhythm sleep problems present in adults with ASD and ID.
PURPOSE: Intellectual disability (ID) and autism spectrum disorder (ASD) are common, co-occurring developmental disorders and are frequently associated with sleep problems. This study aimed to assess the effectiveness and tolerability of agomelatine as a pharmacotherapy for sleep problems in ASD adults with ID. METHOD: A randomised, crossover, triple-blind, placebo-controlled clinical trial, with two three-month periods of treatment starting with either agomelatine or placebo and a washout period of two weeks. Ambulatory circadian monitoring (24 hours/7 days) evaluated total sleep time (TST) as the primary outcome variable. RESULTS: Participants (N=23; 35±12 years old; 83% male) had a median of three (interquartile range (IQR) 1-4) co-morbidities and were taking a median of five (IQR 2-7) prescribed drugs. Before agomelatine or placebo treatment, all subjects presented with insomnia symptoms, including sleep latency (100% abnormal, 55±23 minutes) or TST (55% abnormal, 449±177 minutes), and 66% had circadian rhythm sleep-wake abnormalities with rhythm phase advancements according to the M5 sleep phase marker values. During the three-month agomelatine treatment, night TST significantly increased by a mean of 83 minutes (16% abnormal, 532±121 minutes), together with a phase correction (M5 1:45±2:28 hours vs. 3:15±2:20 hours), improving sleep stability in wrist temperature rhythm (0.43±0.29 vs. 0.52±0.18 AU). Adverse events were mild and transient. CONCLUSIONS: Agomelatine was effective and well tolerated for treating insomnia and circadian rhythm sleep problems present in adults with ASD and ID.