Endogenous melatonin predicts efficacy of exogenous melatonin in consolidation of fragmented wrist-activity rhythm of adult patients with developmental brain disorders: a double-blind, placebo-controlled, crossover study.
OBJECTIVE
: We studied whether the endogenous melatonin patterns in adult patients with developmental brain disorders have any role in response to exogenous melatonin given as a sleep-promoting medicine.


METHODS
: Participants included 15 adults (18-60 years, five females) with developmental brain disorders of varying etiologies, motor handicaps, and long-term history of sleep problems. According to the 24-h patterns of serum melatonin, patients were divided into two subgroups: lower and higher secretors. The pretreatment sleep disorder was characterized by a structured interview, 24-h ambulatory polysomnography and 7-day wrist actigraphy. Patients received 1, 3, or 6mg fast-release melatonin tablets, each for 4 weeks in increasing order, at a constant time of 30min before the desired sleep onset. Similarly, placebos with different codes were given during 3x4 weeks. The 7-day actigraphy was repeated at the end of each drug period. Outcome measures were six different parameters of non-parametric circadian rhythm analysis. Drug effects and 40 confounding/modulating factors were evaluated by applying two-level regression analyses with co-variables.


RESULTS
: Exogenous melatonin decreased the fragmentation of the rest-activity rhythm, increased the day/night ratio of activity and advanced the onset of rest period. The effects on fragmentation and day/night ratio were more pronounced in the lower than higher secretors of melatonin. Other contributing factors in the drug effects were blindness and some features of the original sleep disorder (disrupted cyclicity of the sleep architecture in polysomnography or reported daytime somnolence).


CONCLUSIONS
: Exogenous melatonin consolidated the fragmented rest-activity in about half of the patients. Low endogenous serum melatonin levels at night predicted improvement by the drug. Higher doses were not more effective than the lowest dose.
Laakso
Maija-Liisa
ML
Rinnekoti Foundation, Sleep Research Center, Kumputie 1, FIN-02980 Espoo, Finland. maija-liisa.laakso@saunalahti.fi
Lindblom
Niki
N
Leinonen
Lea
L
Kaski
Markus
M
D000328:Adult; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008607:Intellectual Disability / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000097:blood*; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D017286:Polysomnography / Q000187:drug effects*; D020178:Sleep Disorders, Circadian Rhythm / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D008550:Melatonin