Q&A: What Is Melatonin Replacement Therapy?

I’ve just heard of melatonin replacement therapy, a reader wrote last week to Ask The Savvy Insomniac, and I’m wondering if I should look into it. I’m 61. I never used to have problems with insomnia but now I wake up a lot at night. Over-the-counter melatonin does nothing for me. Is the melatonin used in replacement therapy somehow different?

Melatonin-replacementI’ve just heard of melatonin replacement therapy, a reader wrote last week to Ask The Savvy Insomniac, and I’m wondering if I should look into it. I’m 61. I never used to have problems with insomnia but now I wake up a lot at night. Over-the-counter melatonin does nothing for me. Is the melatonin used in replacement therapy somehow different?

 

A Bit of Background

The hormone melatonin is a major player in the sleep system. Secreted by the pineal gland, it helps create strong biological rhythms that regularly put people to sleep and keep us sleeping through the night.

But often melatonin rhythms grow weaker with age. This occurs for three reasons, says Rüdiger Hardeland in a recent review paper on melatonin in aging and disease:

  • degeneration of neurons in the SCN (a.k.a. the body clock)
  • deterioration of neurons connected to the pineal gland
  • calcification of the pineal gland.

Any of these factors may result in insufficient production of internal melatonin, resulting in insomnia at the beginning or in the middle of the night.

Melatonin Replacement Therapy

It’s worth consideration if melatonin deficiency is your problem. In the US, two options for replacement therapy exist:

  • over-the-counter melatonin supplements, and
  • the prescription drug Rozerem, or ramelteon.

When caused by melatonin deficiency, trouble falling asleep at the beginning of the night responds well to treatment with melatonin supplements, Hardeland says. Over-the-counter melatonin, which is chemically identical to the melatonin produced in your body, may be effective even at low doses (e.g., 0.5 mg) and is the better option for people with sleep onset problems. If taking it close to bedtime doesn’t work, try taking it earlier in the evening. (See my blog on sleepy night owls.)

Replacement Therapy for Trouble Staying Asleep

But at low doses, OTC melatonin supplements are not going to help people who experience frequent wake-ups. The half-life of melatonin is just 20 to 45 minutes. It doesn’t have enough staying power to keep you sleeping through the night.

Higher dosages of melatonin—50 or 100 mg—have been proposed as a therapy for sleep maintenance insomniacs but have yet to be tested, Hardeland says, adding, however, that 300 mg of melatonin administered to ALS patients for up to 2 years was found to be safe.

If sleep maintenance is the issue, ramelteon, a drug more powerful than natural melatonin, is the better option, according to Hardeland. But it may not work for everyone. Trials of ramelteon have shown the improvements it produces in sleep maintenance to be modest. In a recent study of melatonin in elderly patients, the effects of the drug on sleep maintenance were “highly variable.”

A perfect solution for sleep maintenance insomnia caused by melatonin deficiency has yet to be invented. (Circadin, a time-release formulation of melatonin, is available by prescription in Europe. But with this drug, too, effects on sleep maintenance have been modest.)

If you’re a baby boomer or older, though, and your insomnia has developed with age, melatonin deficiency could be part of the problem. Replacement therapy is worth checking out.

The ADHD-Insomnia Connection

Got ADHD? Chances are you’ve got insomnia symptoms, too. About 92 percent of the subjects in a recent study of adults with ADHD reported going to bed late because they were “not tired” or “too keyed up to sleep.”

The sleep problems of adults with ADHD may be due to delayed (and possibly less stable) circadian rhythms. If you’ve got ADHD-related insomnia, treatments aimed at advancing circadian phase may help.

too-much-to-doGot ADHD? Chances are you’ve got insomnia symptoms, too. About 92 percent of the subjects in a recent study of adults with ADHD reported going to bed late because they were “not tired” or “too keyed up to sleep.”

Results of this study, from University of Alabama at Birmingham, show that the sleep problems of adults with ADHD are due to delayed (and possibly less stable) circadian rhythms. (Circadian rhythms are controlled by the body clock.) And, say UAB researchers, delays in sleep timing—and daytime sleepiness—correlate with more severe hyperactive-impulsive and inattentive ADHD symptoms. If you’ve got ADHD-related insomnia, treatments aimed at advancing circadian phase may help.

The Larger Picture

The new findings are in line with the results of other work. Investigators have found, for instance, that ADHD is associated with differences in type or expression of these circadian genes: CLOCK, BMAL1, and PER2.

The body’s production of sleep- and wake-friendly hormones is correspondingly delayed. Investigators in The Netherlands reported in a 2010 study that secretion of melatonin—which helps with sleep at night—began an average of 83 minutes later in adult subjects with ADHD than in adults without. Production of cortisol, which helps with waking up in the morning, is also delayed in people with ADHD.

Across the board, ADHD subjects tend to fall asleep later and wake up later than subjects without ADHD. The medical diagnosis for this delay in falling asleep, when uncomplicated by ADHD, is Delayed Sleep Phase Disorder. Treatments that work for people with DSPD may work for you if you’ve got ADHD.

Better Sleep, Less Sleepiness

  • Bright Light Therapy: A two-hour exposure to bright light (sunlight, or light from a light box) immediately upon waking up every morning is the most effective way to shift sleep to an earlier hour. But this may not jibe with your morning routine. In the winter you wake up to darkness, and continuous use of a light box may not be an option if you have to care for children or get ready for work. Do the best you can by turning up lights in your home full force, and spend as much time as possible by a light box in the first few hours of the day.
  • Melatonin Supplements: Over-the-counter melatonin supplements may also help shift your sleep forward when used every day. But melatonin is not a sleeping pill. It’s effective only when taken well before your internal melatonin secretion begins. For best results, take a tablet 5 to 7 hours before your normal bedtime (rather than right before bedtime, as advised on the label).
  • Rozerem: Ask your doctor about Rozerem (or ramelteon) if you’re interested in going the prescription drug route. Rozerem, approved by the FDA in 2005 for people with trouble falling asleep, purportedly behaves like a super-melatonin. Unlike most sleeping pills on the market today, it’s not known to have many side effects. Take it half an hour before you go to bed.

Shifting circadian rhythms forward may improve your sleep, cut down on daytime sleepiness, and—possibly—help control your ADHD symptoms.

If you’ve got ADHD, how often do you find yourself too keyed up to sleep?