Generalized Anxiety Disorder and Melatonin
Melatonin is a natural hormone that regulates sleep. During daylight, the pineal gland in the brain produces an important neurotransmitter called serotonin. (A neurotransmitter is a chemical that relays messages between nerve cells.) But at night, the pineal gland stops producing serotonin and instead makes melatonin. This melatonin release helps trigger sleep.
The production of melatonin varies according to the amount of light you're exposed to; for example, your body produces more melatonin in a completely dark room than in a dimly lit one.
Melatonin supplements appear to be helpful for people whose natural sleep cycle has been disturbed, such as travelers suffering from jet lag.
Effect of Melatonin on Generalized Anxiety Disorder
As anxiety often prevents an individual from being able to rest and/or fall or stay asleep, melatonin is sometimes used as a treatment to help a person sleep.
Research Evidence on Melatonin
Four double-blind studies performed by Saudi researchers reported that melatonin was useful for reducing anxiety prior to surgery, presumably due to its sedative effects.2,3,95,102 However, other researchers have been unable to confirm these results.99-100
Individuals trying to quit using sleeping pills in the benzodiazepine family may find melatonin helpful. A double-blind, placebo-controlled study of 34 individuals who regularly used such medications found that melatonin at a dose of 2 mg nightly (controlled-release formulation) could help them discontinue the use of the drugs.30 Interestingly, another study failed to find melatonin helpful for reducing benzodiazepine use among people taking drugs in that family for anxiety.58
Side Effects and Warnings
A safety study found that melatonin at a dose of 10 mg daily produced no toxic effects when given to 40 healthy males for a period of 28 days. ^ However, this does not prove that melatonin is safe when taken on a regular basis over the long term. Keep in mind that melatonin is not truly a food supplement but a hormone. As we know from other hormones used in medicine, such as estrogen and cortisone, harmful effects can take years to appear. Hormones are powerful substances that have many subtle effects in the body, and we're far from understanding them fully. While in one small study, use of melatonin over an 8-day period by healthy men did not affect natural release of melatonin or levels of pituitary or sex hormones, ^ another study found effects on testosterone and estrogen metabolism in men and possible impairment of sperm function. ^ Also, a small study in women found possible effects on the important female hormone called LH (luteinizing hormone). ^ Melatonin appears to cause drowsiness and decreased mental attention for about 2 to 6 hours after using it and may also impair balance. ^ For this reason, you should not drive or operate machinery for several hours after taking melatonin. In a study of healthy middle-aged and older adults, however, an extended release version of melatonin, which is said to more closely mimic natural fluctuations of the hormone in the body, did not impair mental ability or driving skills 1 to 4 hours later compared to placebo. ^ In either case, melatonin does not appear to have any "hangover" effects the following day. ^ Based on theoretical ideas of how melatonin works, some authorities specifically recommend against using it in people with depression, schizophrenia, autoimmune diseases, and other serious illnesses. One study in postmenopausal women found evidence that melatonin might impair insulin action and glucose tolerance, suggesting that people with diabetes should not use it. ^ However, another study found melatonin safe and effective for people with diabetes. ^ Because of these contradictions, we suggest that individuals with diabetes seek physician supervision before using melatonin.
Two exceedingly preliminary studies reported by one research group has led to publicized concerns that use of the supplement melatonin might increase night-time asthma. ^ However, one double-blind study of melatonin in people with asthma found evidence of improved sleep without worsening of symptoms. ^ Again, at the current state of knowledge, caution must be advised for people with night-time asthma who wish to try melatonin.
There is some evidence that melatonin may interfere with the ability of blood to clot normally, at least in healthy volunteers, ^ though the clinical significance of this finding is at yet unknown.
Maximum safe dosages for young children, pregnant or nursing women, or those with serious liver or kidney disease have not been established.
References for Research Evidence
- Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth. 1999;82:875-880.
- Naguib M, Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg. 2000;91:473-479.
- Garfinkel D, Zisapel N, Wainstein J, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159:2456-2460.
- Cardinali DP, Gvozdenovich E, Kaplan MR, et al. A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuroendocrinol Lett. 2002;23:55-60.
- Samarkandi A, Naguib M, Riad W et al. Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study. Eur J Anaesthesiol. 2005;22:189-96.
- Kripke DF M D, Kline LE D O, Shadan FF M D Ph D, et al. Melatonin effects on luteinizing hormone in postmenopausal women: A pilot clinical trial NCT00288262. BMC Womens Health. 2006 May 16 [Epub ahead of print].
- Sutherland ER, Ellison MC, Kraft M, et al. Elevated serum melatonin is associated with the nocturnal worsening of asthma. J Allergy Clin Immunol. 2003;112:513-517.
- Campos FL, Da Silva-Junior FP, De Bruin VM, et al. Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2004 Aug 11. [Epub ahead of print]
- Sury MR, Fairweather K. The effect of melatonin on sedation of children undergoing magnetic resonance imaging. Br J Anaesth. 2006 Jun 17 [Epub ahead of print].
- Capuzzo M, Zanardi B, Schiffino E, et al. Melatonin does not reduce anxiety more than placebo in the elderly undergoing surgery. Anesth Analg. 2006;103:121-123.
- Grossman E, Laudon M, Yalcin R, et al. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898-902.
- Turkistani A, Abdullah KM, Al-Shaer AA, et al. Melatonin premedication and the induction dose of propofol. Eur J Anaesthesiol. 2006 Nov 10. [Epub ahead of print]