Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability

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.

Randomised controlled trials of antidepressant and anti-anxiety medications for people with autism spectrum disorder: systematic review and meta-analysis

“…The findings of the included studies are summarised in Table 1. 20–34 Two RCTs on old-generation antidepressant tricyclics were on clomipramine, both of which were small crossover trials ( n = 24 and 36); 24,25 one compared clomipramine with desipramine and placebo, 24 and the other with haloperidol and placebo. 25 One found clomipramine to be marginally significantly better than placebo in treating ASD core symptoms like RRB, 24 but the other one did not show any significant inter-group difference.…”

“…A crossover trial of 23 adults showed improvement in night total sleep time but no other sleep parameters during agomelatine treatment, but not in the placebo phase. 20 No ASD core symptoms were assessed in this study.…”

“…Most studies were on children, but some included data on adults with ASD, and no specific age effect was observable from the data presented in Table 1. 20–34 Of the 15 RCTs, six (40%) used a crossover design. Crossover design may not be ideal to assess long-standing behaviour outcomes, particularly if the washout period is relatively short, as is the case in the included studies.…”

“…), using a proforma modified from the Cochrane template 19 (Supplementary Appendix 4). As people with ASD are likely to be more sensitive to psychotropic medication, we have taken note of the adverse effects described in the included studies 20–34 and presented the findings in Table 1.…”

“…A narrative synthesis of the findings is provided in Table 1. 20–34 Where there were more than one studies, a meta-analysis was carried out. A random-effects odds ratio or standardised mean difference with 95% confidence interval meta-analysis was performed, depending on the type of data gathered.…”