OTC Insomnia Supplements: The Latest Evidence

Darren J. Hein, PharmD


March 15, 2019


Many low-quality studies on the use of L-tryptophan for insomnia were published in the 1970s and 1980s.[8] While results were mixed, most of these studies provided some evidence to support its use. More recently, in 2005, Hudson and colleagues[9] published results from a clinical trial comparing L-tryptophan from either food or supplement sources to placebo in a small group of patients with chronic insomnia. One week of treatment with L-tryptophan in supplement form led to significant improvements in total sleep time (+42 minutes), sleep efficiency (+7.3%), total awake time (-35 minutes), and sleep quality when compared with baseline measurements. However, patients receiving placebo also had significant improvements in many of these metrics, and no significant differences between L-tryptophan and placebo were reported.

While clinical research on L-tryptophan suggests that it is well tolerated, it was removed from the market in the early 1990s due to reports of associated eosinophilia-myalgia syndrome.[8] However, this was probably caused by contaminated product from a single manufacturer, and L-tryptophan returned to the market a decade later.[10]

Because L-tryptophan is a precursor of serotonin, there is some concern about the potential for additive serotonergic side effects, including serotonin syndrome, when used with antidepressants (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors) and other drugs with serotonergic effects.[8,10] Patients who choose to take L-tryptophan for insomnia should be screened for potential interactions.


Valerian's effect on sleep parameters has also been widely studied, but most trials are of low to moderate quality, evaluate valerian alone or in combination with other supplements, assess a variety of doses, and include persons ranging from healthy adults with no sleep issues to elderly patients with chronic insomnia. This makes it difficult to generalize the varied results from these studies to the broader population.

Analyses of clinical trials assessing the utility of valerian for treating insomnia suggest that valerian offers no clinically meaningful improvement in sleep latency, total sleep time, or sleep quality compared with placebo.[4,11,12] Very few of the clinical trials available to date have been suitable for meta-analysis, so results from the most recent analyses fail to tell the whole story. Still, the two largest clinical trials have failed to show significant improvements in sleep with valerian.[13,14] Thus, there is no consistent, high-quality evidence to support recommending valerian for insomnia.

The overall lack of efficacy data may not be enough to persuade patients to consider other interventions, though. Those who wish to give valerian a try should be informed of any potential harms. For the most part, valerian is well tolerated when used short-term, with reported adverse effects minor in nature and comparable to those of placebo.[11,12] However, one study reported that the rate of diarrhea with valerian is more than double that of placebo (18% vs 8%, P = .02)[14]; clinicians should advise patients accordingly.


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