Daniel Carlat, MDDr. Carlat has disclosed that he has no significant relationships with or financial interests in any commercial companies pertaining to this educational activity.
Any of you who choose to do an informal survey of your patients will be surprised how many are taking a non-prescribed sleeping aid. Often this is an antihistamine, but patients are increasingly turning to natural alternatives.
In this article, we focus on melatonin and valerian. For important information on kava, please see the interview with Dr. David Mischoulon in this issue.
Melatonin. Melatonin is produced in the pineal gland, and levels rise as night approaches, peaking at about 2 AM and becoming almost undetectable during the day. The hormone’s function is to prepare us biochemically for sleep.
In general, melatonin is considered the definitive treatment for jet lag and jet lag syndromes, such as those suffered by medical residents and other masochists who involve themselves in shift work. An early study compared the effects of 5 mg of melatonin with placebo in travelers flying from San Francisco to London; melatonin prevented jet lag symptoms in all subjects who took it (Brit Med J 1986; 292:1170). A recent review of 10 randomized trials of melatonin in jet lag found it effective at between 2 mg and 5 mg taken the night of arrival (Cochrane Library 2002; disk issue 4:CD001520).
When used for other types of insomnia, however, the evidence for melatonin is mixed. A recent small study of patients with primary insomnia found no benefit over placebo, but the dosing was low, no higher than 1 mg QHS (J Psychiatry Neurosci 2003; 28:191- 196). A larger study of 157 patients with Alzheimer's Disease and comorbid insomnia found no difference between melatonin 2.5 mg, 10 mg, or placebo (Sleep 2003; 26:893-901).
On the positive side, melatonin does appear helpful for insomnia in depressed patients on SSRIs, as demonstrated by a placebo-controlled trial comparing 5 mg of slow-release melatonin with placebo (Am J Psychiatry 1998; 155:1119-1121). And it appears to be both safe and effective in children with chronic insomnia (J Am Acad Child Adolesc Psychiatry 2003; 42:1286-1293).
Dosing seems to be idiosyncratic, with some patients complaining bitterly of morning hangover at 0.5 mg, while others are wide awake hours after ingesting 6 mg. Many patients begin with 1 mg QHS, and either increase or decrease the dose from there. Side effects are minimal, unless you make the mistake of taking it during the day. And, at about a nickel a dose, it's dreamily cheap.
Melatonin It is considered the definitive treatment for jet lag, but efficacy for other causes of insomnia is less clear.
Valerian. Valerian stinks.
No, this is not an official evaluation of its efficacy as a hypnotic. It's a statement of fact, based on its volatile oils which impart a "distinctive" odor and aftertaste. But that may be a small price to pay for a good night's sleep.
Valerian is a perennial flowering plant, and the name is derived from the Latin valere, "to be in good health." Most formulations sold are extracts of the valerian root. If you put such extracts through your basement chemistry laboratory, you'd find a plethora of chemicals and no one has the slightest idea which one causes us to drift off. Many believe that the neurotransmitter GABA must be involved, and will cite evidence to prove it. Reading these papers, however, may someday win FDA approval as a dangerously strong hypnotic in itself.
Many studies of highly varying quality have been published seeking to document the hypnotic effects of valerian. Most of the double-blind controlled studies have been positive. Valerian has been shown to decrease sleep latency (the number of minutes required to fall asleep), improve the subjective sense of sleep, and to improve slow wave ("deep") sleep (American Family Physician 2003; 67:1755-1758). Valerian has been compared head-to-head with Serax (oxazepam) 10 mg QHS in 202 patients with insomnia, and the herbal was every bit as effective as the benzo (Eur J Med Res 2002; 25:480-486).
Most studies have used valerian root extract at 300 to 600 mg, taken about an hour before bedtime. It seems safe, with few side effects, no drug-drug interactions, and no addictive potential. And it's very cheap, coming in at around a dime per dose, depending on where you buy it. Now that doesn't stink.
TCR VERDICT: Melatonin for jet lag; Valerian’s worth a try for everything else!