Effect of Melatonin Dosage on Sleep Disorder in Tuberous Sclerosis Complex

Abstract

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. (J Child Neurol 2005;20:78—80).

Get full access to this article

View all access options for this article.

References

O'Callaghan Fjk , Shiell AW , Osborne JP , Martyn CN : Capture-recapture analysis to estimate the prevalence of tuberous sclerosis. Lancet 1998 ;351:1490.

O'Callaghan F. , Osborne JP : Advances in the understanding of tuberous sclerosis. Arch Dis Child 2000 ;83:140—142.

Hunt A. : Development, behaviour and seizures in 300 cases of tuberous sclerosis . J Intellect Disabil Res 1993;37:323—339.

Hunt A. , Stores G. : Sleep disorder and epilepsy in children with tuberous sclerosis; a questionnaire-based study. Dev Med Child Neurol 1994;36:108—115.

Bruni O. , Cortesi F. , Giannotti F. , Curatolo P. : Sleep disorders in tuberous sclerosis: A polysomnographic study. Brain Dev 1995;17: 52—56.

Weitzman ED , Czeisler CA , Colman RM , et al: Delayed sleep-phase syndrome, a chronobiological disorder with sleep-onset insomnia. Arch Gen Psychiatry 1981;38:737—746.

Arendt J. , Aldous M. , English J. , et al: Some effects of jet-lag and their alleviation by melatonin. Ergonomics 1987;30:1379—1393.

Jan JE , Espezel H. , Appleton RE : The treatment of sleep disorder with melatonin. Dev Med Child Neurol 1994;36:97—107.

McArthur AJ , Budden SS : Sleep dysfunction in Rett syndrome: A trial of exogenous melatonin treatment . Dev Med Child Neurol 1998;40: 186—192.

10.

O'Callaghan FJ , Clarke AA , Hancock E. , et al: Use of melatonin to treat sleep disorders in the tuberous sclerosis complex. Dev Med Child Neurol 1999;41:123—126.

11.

Camfield P. , Gordon K. , Dooley J. , Camfield C. : Melatonin appears ineffective in children with intellectual deficits and fragmented sleep: Six “n of 1” trials. J Child Neurol 1993;11:341—343.

12.

Quine L. : Sleep problems in children with mental handicap. J Ment Defic Res 1991;35:269—290.

13.

Stores G. : Sleep disorders in children with mental handicap. J Child Psychol Psychiatry 1992;33:1303—1317.

14.

Tay AF : Melatonin: Effects on brain function. Adv Biochem Psychopharmacol 1974;11:315—324.

15.

Sudgen D. : Psychopharmocological effects of melatonin in mouse and rat. J Pharmacol Exp Ther 1983;227:587—591.

16.

Maurizi CP : Could supplementry dietary tryptophan and taurine prevent epileptic seizures? Med Hypotheses 1995;18:411—415.

17.

Molina-Carballo A. , Acuna-Castroviejo D. , Rodriguez-Cabezas T. , Monoz-Hoyos A. : Effects of febrile and epileptic convulsions on daily variations in plasma melatonin concentration in children. J Pineal Res 1994;16:1—9.

18.

Schapel GJ , Beran RG , Kennaway DL , et al: Melatonin response in active epilepsy. Epilepsia 1995;36:75—78.

19.

Sheldon SH : Pro-convulsant effects of oral melatonin in neurologically disabled children . Lancet 1998;351:1254.

20.

Peled N. , Shorer Z. , Peled E. , Pillar G. : Melatonin effect on seizures in children with severe neurological deficit disorders. Epilepsia 2001;42:1208—1210.

21.

Hancock E. , O'Callaghan F. , English E. , Osborne J. : Melatonin Excretion in Normal Children and in Tuberous Sclerosis Complex with Sleep Disorder Responsive to Melatonin. J Child Neurol 2005;20:21—25.