Acute increase in urinary 6-sulfatoximelatonin after clomipramine, as a predictive measure for emotional improvement.
Nocturnal melatonin pineal output is triggered by sympathetic outflow. Antidepressants that block norepinephrine neuronal uptake should increase pineal function. This can be monitored by measuring 6-sulfatoximelatonin (aMT6s), the main melatonin metabolite, in the urine. In this study, we compared the excretion of aMT6s before (baseline), one, and 21 days after administration of clomipramine to healthy subjects (n = 32). At the end of treatment, subjects were divided into responders (n = 12) and non-responders (n = 20) according to the improvement in their emotional state in three out of four domains (interpersonal tolerance, efficiency, well-being and feeling different from the usual self). There was no difference in aMT6s before clomipramine between responders and non-responders in any of the time intervals analysed (06:00-12:00, 12:00-18:00, 18:00-24:00 and 24:00-06:00 hours). At day one, but not at day 21, the fraction of aMT6s excreted during the time interval 24:00-06:00, relative to the total amount excreted by each subject per day, was significantly higher (P = 0.0287) than baseline (0.57 +/- 0.04) in responders. No significant difference was observed in non-responders. The increase in pineal function induced by clomipramine was restricted to day one, indicating that long-lasting adaptation restores pineal function. In addition, the day one increase in aMT6s was significantly increased only in the responders group, raising the possibility that the blocking of neuronal uptake is predictive of emotional improvement.
Markus
R P
RP
Laboratory of Chronopharmacology, Institute of Biosciences, Universidade de São Paulo, São Paulo, Brazil. rpmarkus@usp.br
Franco
D G
DG
Carvalho
L A
LA
Gentil
V
V
Gorenstein
C
C
D000328:Adult; D000704:Analysis of Variance; D002940:Circadian Rhythm / Q000502:physiology; D002997:Clomipramine / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000652:urine; D008875:Middle Aged; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D016037:Single-Blind Method; D013997:Time Factors
C054513:6-sulfatoxymelatonin; D008550:Melatonin; D002997:Clomipramine