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.
Keywords: Autism spectrum disorder; agomelatine; ambulatory circadian monitoring; circadian rhythm; sleep problems.