Why Melatonin Works for Some and Not for Others

Summarized by Robert W. Griffith, MD
October 1, 2004

Introduction

Almost one in three people over 65 complain of insomnia. Usually it's quite hard for the doctor to find a good reason for poor sleep in older persons, so that they tend to turn to over-the-counter drugs or alternative remedies. One of the most popular alternative medicines is melatonin. This is because melatonin, long recognized as a sleep regulator, is less plentiful in the elderly. Some people say melatonin therapy is wonderful, while others find it doesn't work, or it makes them 'nervous'. European scientists have found a possible explanation for the variability in melatonin's effectiveness as a treatment for insomnia. Their findings are published in the American Journal of Medicine, and are summarized here.

What was done

The excretion in the urine of one of melatonin's major breakdown products, 6-sulfatoxymelatonin, was studied in insomnia patients, in normal volunteers of a similar age, and in younger normal volunteers. The patients had to be over 55, free of depression, and with no obvious medical cause for their insomnia. Complete urine samples were collected from 10:00 pm to 10:00 am, and from 10:00 am to 10:00 pm.

Most of the insomniac patients were then treated with a dummy tablet (placebo) for two weeks, followed by extended-release melatonin tablets¹ for 3 weeks, to determine if they had improvement in their quantity and quality of sleep, using a well-recognized scoring system (the Leeds Sleep Evaluation Questionnaire).

What was found

There were 517 patients, 29 age-matched normal volunteers, and 30 younger volunteers enrolled in the study. At baseline, the average nighttime excretion of the melatonin breakdown product was 9 micrograms (per night) in the insomniac patients, 18 micrograms in the older volunteers, and 24 micrograms in the young volunteers. Clearly, the insomniacs had a reduced excretion of this breakdown product, suggesting a reduced production of melatonin in these people.

A total of 372 insomniac patients went on to receive the placebo for 2 weeks, followed by 2 mg of extended-release melatonin for 3 weeks, taken every night between 9:00 and 11:00 pm.

Results of the questionnaire showed that, in general, melatonin therapy improved the main symptoms of insomnia. Patients with lower levels of melatonin production at baseline were linked to a higher response to melatonin treatment in 3 of the 4 main areas: getting to sleep, quality of sleep, and alertness and behavioral integrity ('getting things together') the next morning.

The insomniac patients were classified into 'low excreters' or 'high excreters' of melatonin breakdown product, according to whether their nighttime amount was below or above 3.5 micrograms. In the 112 low excreters there were 58% responders to melatonin treatment, compared with 47% in the 260 high excreters.

What this means

In older people who have difficulty sleeping, poor production of melatonin is linked with a better response to melatonin treatment. Those with an adequate production of melatonin responded less well. This helps explains why some people may find melatonin effective, while others don't. Certainly, if there are no serious causes for insomnia in older people, a trial of melatonin may be worthwhile. However, as with all non-regulated supplements, it's important to make sure that it comes from a reliable manufacturer who can guarantee its quality and purity.

Source

• Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. D. Leger, M. Laudon, N. Zisapel, Am J Med, 2004, vol. 116, pp. 91--95

Footnotes
1. The medication used was Circadin®, made by Neurim Pharmaceuticals, Tel Aviv, Israel.

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