Document Detail

Loss of response to melatonin treatment is associated with slow melatonin metabolism.
MedLine Citation:
PMID:  20576063     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this loss of response is associated with slow melatonin metabolism. METHOD: In this study, we determined melatonin clearance in two female (aged 61 and 6 years) and one male (aged 3 years) patients who had chronic insomnia, late melatonin onset and mild ID, and whose sleep quality worsened a few weeks after initial good response to melatonin treatment, suggesting melatonin tolerance. After a 3-week washout period, patients received melatonin 1.0, 0.5 or 0.1 mg, respectively. Salivary melatonin level was measured just before melatonin administration, and 2 and 4 h thereafter. After this melatonin clearance test, melatonin treatment was resumed with a considerably lower dose. RESULTS: In all patients melatonin concentrations remained >50 pg/mL at 2 and 4 h after melatonin administration. After resuming melatonin treatment sleep problems disappeared. The same procedure was followed in three patients who did not show loss of response to melatonin after 6 months of treatment. In all patients in the control group melatonin concentrations decreased between 2 and 4 h after melatonin administration with a mean of 83%. CONCLUSION: We hypothesise that loss of response to melatonin treatment can be caused by slow metabolisation of exogenous melatonin. As melatonin is metabolised in the liver almost exclusively by cytochrome P450 enzyme CYP1A2, this slow melatonin metabolism is probably due to decreased activity/inducibility of CYP1A2. In patients with loss of response to melatonin, a melatonin clearance test should be considered and a considerably dose reduction is advised.
W Braam; I van Geijlswijk; Henry Keijzer; Marcel G Smits; Robert Didden; Leopold M G Curfs
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of intellectual disability research : JIDR     Volume:  54     ISSN:  1365-2788     ISO Abbreviation:  J Intellect Disabil Res     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-25     Completed Date:  2010-10-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206090     Medline TA:  J Intellect Disabil Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  547-55     Citation Subset:  IM    
's Heeren Loo Zuid-Veluwe, Wekerom, Postbus 75, 6710 BB Ede, The Netherlands.
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MeSH Terms
Child, Preschool
Drug Tolerance
Melatonin / blood*,  therapeutic use*
Mental Retardation / blood*,  drug therapy*
Metabolic Clearance Rate / physiology
Middle Aged
Saliva / chemistry
Sleep Initiation and Maintenance Disorders / blood*,  drug therapy*
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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