Saturday, May 22, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
10:00 AM
Background:
Retrospective and small open label studies have shown that supplemental melatonin promotes sleep in children with autism spectrum disorders (ASD). However, information on effective dose, and time required to reach it, has not been fully explored.
Objectives:
In preparation for a large multicenter randomized controlled trial, we are carrying out a pilot study of supplemental melatonin in children with ASD. A major objective is to define the relation of sleep latency (SL; minutes to fall asleep) to melatonin dose over time.
Methods:
Children were ages 4-10 years, with a clinical diagnosis of ASD based on DSM-IV criteria. Diagnosis was confirmed on the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. All children had sleep delay, defined as inability to fall asleep within 30 minutes at least 3 nights a week. Medical causes of insomnia and primary sleep disorders were addressed prior to enrollment. Children on medications which affect melatonin pharmacokinetics were excluded. Objective measures of sleep were measured over 17 weeks with actigraphy in conjunction with sleep diaries. All children received one week of baseline actigraphy followed by two weeks of an inert flavored liquid 30 minutes before bedtime, to acclimate them taking a liquid medication at bedtime. At week 3, children began 1 mg of supplemental melatonin (Natrol ®). The child’s response to melatonin was reevaluated every three weeks based on mean SL. Dose was increased every three weeks (from 1 mg, to 3 mg, to 6 mg, to 9 mg) until the child reached a satisfactory response, defined as SL within 30 minutes on 5 or more nights in the week. Once a satisfactory response was achieved, the child remained on that melatonin dose for the remainder of the 17 weeks.
Results:
Fifteen children were included, with mean age of 6.5 years [standard deviation (SD) = 2.2]. Mean sleep latency was 44.5 minutes (SD = 23.8) at baseline and 23.7 minutes (SD = 8) at the end of study; p = 0.05, Wilcoxon-signed rank test. All children achieved a satisfactory response. The percentage of children achieving a satisfactory response (SL within 30 minutes on 5 or more nights a week) was 47% in week 4 (corresponding to the first week of the 1 mg dose) and 67% by week 7 (corresponding to the first week of the 3 mg dose). Of the five other children, three reached a satisfactory response by the end of 3 mg dosing period and two reached a satisfactory response at 6 mg. No children required 9 mg dosing. In the overall sample, there was no significant decrease in sleep latency in the 2nd and 3rd weeks, as compared to the first week, of each dosing period.
Conclusions:
In this pilot work, we documented that supplemental melatonin decreases sleep latency, as documented by actigraphy. Low dose melatonin (3 mg or below) appears effective in reducing SL in the majority of children, with a relatively rapid dose response. Randomized clinical trials of supplemental melatonin appear warranted.
Retrospective and small open label studies have shown that supplemental melatonin promotes sleep in children with autism spectrum disorders (ASD). However, information on effective dose, and time required to reach it, has not been fully explored.
Objectives:
In preparation for a large multicenter randomized controlled trial, we are carrying out a pilot study of supplemental melatonin in children with ASD. A major objective is to define the relation of sleep latency (SL; minutes to fall asleep) to melatonin dose over time.
Methods:
Children were ages 4-10 years, with a clinical diagnosis of ASD based on DSM-IV criteria. Diagnosis was confirmed on the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. All children had sleep delay, defined as inability to fall asleep within 30 minutes at least 3 nights a week. Medical causes of insomnia and primary sleep disorders were addressed prior to enrollment. Children on medications which affect melatonin pharmacokinetics were excluded. Objective measures of sleep were measured over 17 weeks with actigraphy in conjunction with sleep diaries. All children received one week of baseline actigraphy followed by two weeks of an inert flavored liquid 30 minutes before bedtime, to acclimate them taking a liquid medication at bedtime. At week 3, children began 1 mg of supplemental melatonin (Natrol ®). The child’s response to melatonin was reevaluated every three weeks based on mean SL. Dose was increased every three weeks (from 1 mg, to 3 mg, to 6 mg, to 9 mg) until the child reached a satisfactory response, defined as SL within 30 minutes on 5 or more nights in the week. Once a satisfactory response was achieved, the child remained on that melatonin dose for the remainder of the 17 weeks.
Results:
Fifteen children were included, with mean age of 6.5 years [standard deviation (SD) = 2.2]. Mean sleep latency was 44.5 minutes (SD = 23.8) at baseline and 23.7 minutes (SD = 8) at the end of study; p = 0.05, Wilcoxon-signed rank test. All children achieved a satisfactory response. The percentage of children achieving a satisfactory response (SL within 30 minutes on 5 or more nights a week) was 47% in week 4 (corresponding to the first week of the 1 mg dose) and 67% by week 7 (corresponding to the first week of the 3 mg dose). Of the five other children, three reached a satisfactory response by the end of 3 mg dosing period and two reached a satisfactory response at 6 mg. No children required 9 mg dosing. In the overall sample, there was no significant decrease in sleep latency in the 2nd and 3rd weeks, as compared to the first week, of each dosing period.
Conclusions:
In this pilot work, we documented that supplemental melatonin decreases sleep latency, as documented by actigraphy. Low dose melatonin (3 mg or below) appears effective in reducing SL in the majority of children, with a relatively rapid dose response. Randomized clinical trials of supplemental melatonin appear warranted.