Posted by Ron Hill on January 20, 2001, at 11:08:13
In reply to Re: Melatonin - How much ?, posted by SLS on January 18, 2001, at 18:53:17
Scott,
I found the following study interesting and I thought you might find it worth reading (if you have not already seen it):
•For the adjunctive treatment of insomnia† related to major depression:
Oral dosage (extended-release formulations):
Adults: 5—10 mg PO taken 1—2 hours prior to habitual bedtime. In one 4-week placebo-controlled study of 19 patients with major depressive disorder treated with fluoxetine, the sub-group of 10 patients who received concomitant slow-release melatonin at 9 pm for sleep reported significantly improved sleep quality scores versus the patients receiving fluoxetine alone. Melatonin treatment avoided the need for additional sleep medications. No differences in the rates of improvement of depressive symptoms or side effects were reported between the two groups.[2100]Reference [2100]:
Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry 1998;155:1119—21.I find it interesting that this study reports positive results using *extended release* melatonin. As a layman, I would have expected the patients in this study to have experienced simillar "next day problems" as you and I both experienced using a multiple dosing trial. However, I don't know the length of time the extended release continues to provide exogenous melatonin to the subject's brain. If the extended release continues its action well into the night (i.e.; past 2:00 or 3:00 am), I don't understand how the circadian rhythm delay issues were avoided. Know what I mean? What do you think?
-- Ron
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> I don't know if the following represents the reason for the 3:00am limit. Melatonin is secreted by a small structure within the brain called the pineal gland. Melatonin is manufactured from serotonin. Like so many other endocrine functions, melatonin secretion follows a daily or "circadian" rhythm. Melatonin levels begin to rise during the evening and continue to rise after going to sleep. During the night, melatonin reaches its peak levels at around 2:00am. Thereafter, secretion drops off quickly and reaches a minimum by morning. To add melatonin to the system after the circadian scheduled 2:00am peak would disturb the system of. When the peak melatonin concentration is artificially moved to a time that is later than scheduled, the circadian clock may become "delayed".
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> A circadian rhythm delay is sometimes known as "jet lag". It is also capable of eliciting or making worse a depressive state. By contrast, a rhythm advance can have antidepressant effects. This is how sleep deprivation works in some people to produce a transient antidepressant response. It has been discovered that it is not necessary to undergo a total night's deprivation to accomplish this. The effect can be produced by going to bed the normal time and waking up between 2:00am and 3:00am and remaining awake until the following evening.
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> For oral preparations of melatonin, I can't see taking it after 1:00am so as to not produce a phase delay. I don't know the exact amount of time it takes for oral administration to produce a peak concentration in the target tissues. If necessary, however, I should think that sublingual administration would be alright to take up until 2:00am. I have no idea when is the optimal time to take melatonin. I have seen recommendations to take it 20 minutes before going to bed.
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> Dove was kind enough to tell me that melatonin can produce depression. I didn't know that.
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> - Scott
poster:Ron Hill
thread:51473
URL: http://www.dr-bob.org/babble/20010111/msgs/52084.html