Use of melatonin to treat sleep disorders in tuberous sclerosis
sleep disturbance/disorders; tuberous sclerosis; pharmacologic intervention; melatonin
The results of a therapeutic trial of the use of melatonin in patients with tuberous sclerosis complex who also have severe sleep problems are reported. We used a randomized double-blind placebo-controlled crossover design. Seven patients with confirmed diagnoses of tuberous sclerosis and significant sleep disorder were recruited. We employed three outcome measures: total sleep time, time to sleep onset, and number of awakenings. Patients treated with melatonin had a small but clinically significant improvement in total sleep time (mean improvement 0.55 hours, P < 0.05). They also tended to have an improvement in sleep-onset time but this did not reach statistical significance. Melatonin, in this trial, had no discernible effect on sleep fragmentation. We conclude that melatonin does have a beneficial effect in prolonging the total sleep time of patients with tuberous sclerosis and sleep disorder and that further trials are necessary to investigate the issues of optimal dosage, tolerance, and possible interactions with other medications.
O'Callaghan F J K; Clarke A;Hancock E; Hunt A B A; Osborne J P
Developmental Medicine and Child Neurology
1999
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1017/S0012162299000237" target="_blank" rel="noreferrer noopener">10.1017/S0012162299000237</a>
Effect of melatonin dosage on sleep disorder in tuberous sclerosis complex
Male; Treatment Outcome; Dose-Response Relationship Drug; Child; Humans; Adult; Cross-Over Studies; Female; Child Preschool; Infant; Administration Oral; Double-Blind Method; Tuberous Sclerosis/complications; Antioxidants/pharmacology/therapeutic use; Melatonin/pharmacology/therapeutic use; Sleep Wake Disorders/drug therapy/etiology; sleep disturbance/disorders; tuberous sclerosis; pharmacologic intervention; melatonin
We report a randomized, double-blind, controlled, crossover trial investigating the response to oral melatonin using two dose regimens in patients with sleep disorders associated with tuberous sclerosis complex. Eight outpatients with tuberous sclerosis complex and sleep disorder received either 5 or 10 mg of melatonin. Sleep latency, total sleep time, number of awakenings, and seizure frequency were recorded in sleep and seizure diaries. No evidence of a dose effect between 5 and 10 mg was seen with respect to any outcome measure. (The 5 mg results are given first: sleep latency, 86 and 76 minutes; total sleep time, 8 hours, 57 minutes and 9 hours, 4 minutes; and sleep fragmentation, 0.8 and 1.0). This study might have missed a small beneficial effect of 10 mg melatonin. We propose that an initial trial of 5 mg melatonin is worth considering in patients with tuberous sclerosis complex and sleep disorder.
Hancock E; O'Callaghan F; Osborne J P
Journal of Child Neurology
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1177/08830738050200011302" target="_blank" rel="noreferrer noopener">10.1177/08830738050200011302</a>
Melatonin excretion in normal children and in tuberous sclerosis complex with sleep disorder responsive to melatonin
Circadian Rhythm; Male; Case-Control Studies; Child; Humans; Adolescent; Female; Child Preschool; Administration Oral; Reference Values; Tuberous Sclerosis; Antioxidants; Melatonin; Sleep Wake Disorders; Antioxidants/pk [Pharmacokinetics]; Circadian Rhythm; Melatonin/aa [Analogs & Derivatives]; Melatonin/pk [Pharmacokinetics]; Sleep Wake Disorders/co [Complications]; Tuberous Sclerosis/co [Complications]; 0 (Antioxidants); 2208-40-4 (6-sulfatoxymelatonin); Antioxidants/ad [Administration & Dosage]; JL5DK93RCL (Melatonin); Melatonin/ad [Administration & Dosage]; Melatonin/ur [Urine]; Sleep Wake Disorders/pp [Physiopathology]; Tuberous Sclerosis/pp [Physiopathology]; sleep disturbance/disorders; trajectory; characteristics; melatonin
To determine normal melatonin excretion patterns in healthy children without sleep disorder and to compare these with those of patients with tuberous sclerosis complex and sleep disorder responsive to exogenous melatonin, we measured 6-sulfatoxymelatonin excretion in 21 healthy children and in 7 patients with tuberous sclerosis complex and sleep disorder responsive to melatonin (a 5 mg oral dose increasing total sleep time). Total excretion, cosinor percentage, and acrophase time of 6-sulfatoxymelatonin excretion were estimated. In normal children, total 6-sulfatoxymelatonin excretion was range 11.1 to 40.2 microg (mean 19.0 microg, SD 7.4 microg); cosinor percentage rhythm range was 52.9% to 100% (mean 87%, median 94%); and acrophase time range was 23 hours, 54 minutes to 10 hours, 42 minutes (mean 5 hours, 54 minutes; median 4 hours, 12 minutes). Fifth and 95th percentiles were 11.1 to 29.0 microg, 57.8% to 99.9%, and 2 hours, 1 minute to 10 hours, 4 minutes. In tuberous sclerosis, normal patterns of melatonin excretion were seen in responders. Circadian patterns of melatonin excretion were similar in children and adults. We propose that exogenous melatonin can act by a simple sedative action.
Hancock E; O'Callaghan F; English J; Osborne J P
Journal of Child Neurology
2005
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1177/08830738050200010301" target="_blank" rel="noreferrer noopener">10.1177/08830738050200010301</a>