Valerian for the Treatment of Insomnia

By Felise Milan, MD, and Ronit Fallek, BA

Insomnia is defined as a condition of unsatisfactory quality or quantity of sleep. It is characterized by difficulty with initiating or maintaining sleep or non-refreshing sleep associated with some form of daytime sequelae (i.e., fatigue, poor concentration, memory problems).1 Cognitive-behavioral treatment for insomnia is effective in many patients but can be time-consuming and costly.2 Effective pharmacotherapy is associated with daytime sedation and dependence with continued use.3 Valerian is a popular herbal therapy for insomnia. In 2002, retail sales of valerian in the United States were just over $8 million.4

Insomnia

One-third of Americans report some type of sleep problem.5 Approximately 25% of the general population reports occasional insomnia.5 The prevalence of chronic insomnia is 10%,1,5 with insomniacs rarely visiting a physician to discuss their sleep problem.5 The prevalence of chronic insomnia among primary care patients is between 15-20%.6

Insomnia can be secondary to another condition (most commonly psychiatric disorders) or an independent disorder. The definition and categorization of primary insomnia varies with the outcomes used to measure it. Some studies define insomnia purely based on patients’ reported symptoms (i.e., sleep diary). Others measure symptoms associated with objective daytime consequences or with polysomnography.

Although many consider EEG changes on polysomnography to be the gold standard to measure sleep, others point out that sleep is not the same in the laboratory as it usually is at home.7,8 In addition, there are varying degrees of discrepancy between subjective complaints of insomnia and objective measures of EEG sleep.7

Insomnia is more common in women than men. This may be due to hormonal changes unique to women. This theory is supported by an association of sleep disturbance in the late-luteal (premenstrual) phase, pregnancy, and perimenopause.9 It has been hypothesized that the gender differences in the prevalence of insomnia can be accounted for by the gender differences in the prevalence of anxiety and depression.10

Valerian

Valerian root (Valeriana officinalis L.), native to eastern, southeastern, and east-central Europe, is utilized widely in Europe and the United States as a mild sedative and sleep-enhancing agent. Ancient authors praised valerian for its diuretic and epilepsy-abetting properties.11 Valerian acquired its usage as a hypotensive, anticonvulsive sedative, and hypnotic12 by the late 19th century. Valerian was listed as an official remedy in the U.S. Pharmacopoeia from 1820-1936, and in the National Formulary from 1888-1946,11 but was dropped with the introduction of barbiturates.12 In 1985, Commission E, responsible for herbal medicine regulation in Germany, approved valerian as an over-the-counter remedy for "states of unrest and nervous sleep disturbances,"12 securing the plant’s already widespread use in Europe.

Mechanism of Action

The mechanisms of valerian’s biological effects are not known precisely. Valerian contains sesquiterpenes of the volatile oil (including valerenic acid), iridoids (valepotriates), alkaloids, furanofuran lignans, and free amino acids such as gamma-amino butyric acid (GABA), tyrosine, arginine, and glutamine.13 Valepotriates and valerenic acid both have sedative effects,13 while valerenic acid and unknown elements appear to enhance GABA secretion and to inhibit its uptake.12 Recent research has identified the flavanoids hesperidin (HN), which has sedative and sleep-enhancing properties, and 6-methylapigenin, which has anxiolytic effects and seems to potentiate HN.14 However, scientists maintain that valerian’s actions most likely result from the synergistic effects of all of its chemical components working in tandem.

Effectiveness of Valerian for Insomnia

Valerian has been evaluated for the treatment of chronic and episodic insomnia, as well as for its effect on sleep in normal sleepers. A systematic review of the evidence on valerian focused upon nine randomized clinical trials investigating different valerian extracts. Three of these trials investigated the effects of repeated administration of valerian. All three showed some effect of valerian on different sleep parameters including improved sleep latency15 and an increase in slow-wave sleep.16 The six other trials investigated responses to a single dose of valerian. The largest study compared the responses of 128 volunteers to three doses of valerian, three doses of a commercial combination of valerian and hop flower extract (Hova), and three placebo doses administered on nine non-consecutive nights. Sleep latency and quality were rated as significantly improved with valerian compared to placebo. Results were particularly strong for participants who described themselves as poor sleepers.17

Another small study found a significant decrease in sleep latency (as measured with wrist-worn activity meters) in eight volunteers with mild insomnia on the nights they took either 450 mg or 900 mg of an aqueous valerian extract when compared to placebo.18 The other four trials used eight to 10 healthy volunteers each, and while two found a significant benefit from valerian19,20 the other two largely were negative.20,21 However, the authors of the review considered the positive studies to have the greatest methodological quality.3

A double-blind crossover study compared two valerian extracts in 20 insomnia patients. Subjects were given 450 mg of Valeriana edulis (commonly known as Valeriana mexicana) or 450 mg of Valeriana officialis on four consecutive nights. Both valerian extracts increased the amount of REM sleep. Only V. edulis reduced the number of awaking episodes. Other polysomnographic variables showed a tendency toward improved sleep efficiency but did not achieve statistical significance.22

Two double-blind, randomized, placebo-controlled trials have evaluated the valerian extract Sedonium. The first trial demonstrated no effect on sleep parameters in the lab after a single dose (600 mg), but showed a significantly greater improvement in slow-wave sleep latency for valerian over placebo when administered nightly for 14 days. Overall sleep efficiency improved significantly over baseline, but equally for the two groups.23 The second is a more recent multicenter trial comparing Sedonium with 10 mg of oxazepam over a six-week period in 202 patients with insomnia. Valerian produced equivalent efficacy to oxazepam in increasing patients’ perception of sleep quality as measured by a variety of instruments used to assess sleep.24

Safety of Valerian

The literature shows that short-term valerian use (less than six weeks) is quite safe. There are no long-term studies on valerian. Reports of adverse effects are rare but could include headache, gastrointestinal irritation, or dizziness.13 Overdose is unlikely, even in high doses, but could cause ataxia, hypothermia, decreased sensibility, hallucinations, and increased muscle relaxation.12 Commission E reports no drug interactions, but valerian’s sedative qualities hypothetically could potentiate barbiturates, benzodiazepines, opiates, anesthetics, and other central nervous system depressants such as alcohol.12,13,25 Valerian extends sleep induced by thiopental and pentobarbital.12

A few studies have evaluated alertness and performance the morning after a valerian dose. Only one study found minor deteriorations after one dose. This effect, however, was not detected after repeated administration. There does not seem to be a serious hangover effect with valerian as often is seen with benzodiazepines.3,13 There has been one case report of delirium and cardiac complications upon cessation of valerian after prolonged use.26 Limited data exist that valerian may attenuate some of the negative effects of benzodiazepine withdrawal on sleep.27 Valepotriates have shown in vitro cytotoxic and mutagenic effects in high doses.11,12 Pregnant women should not ingest valerian.

Formulations and Dosage

Valerian root generally is ingested as an alcohol extract or in capsule or pill form, owing to the root’s pungent flavor. Recommended doses are one teaspoon of liquid extract in water; 300-600 mg in capsules, depending on the brand; or 2-3 g of the dried root, simmered in two cups of boiling water until the water is reduced by one-half (decoction), or steeped in a cup of hot water for at least 15-20 minutes (infusion). Preparations should be ingested 30 minutes to two hours before bedtime, and should be followed by restful activity.

Conclusion

In summary, valerian appears to have some efficacy in improving quality of sleep when administered continuously over a minimum of one to two weeks, although it might be effective in some patients when used intermittently as needed. It seems to be more effective in those with insomnia than normal sleepers. However, it is very difficult to make firm determinations as the literature varies widely with regard to methodology and kind of valerian extract used. The optimal study setting (home vs. sleep lab) is unclear. Although objective outcome measures are obtained more easily in the laboratory, obviously it is not the natural sleep environment. Some argue that the lab may hamper sleep for normal sleepers but improve it for insomniacs by eliminating the usual environmental cues that reinforce their insomnia.3

The active components responsible for valerian’s therapeutic effects remain unclear. Valerian extracts vary widely with regard to the amount of valepotriates present. For example, many aqueous extracts used in the studies discussed contained no valepotriates. It is difficult, therefore, to compare results of studies using different doses and extracts.

Valerian appears to be safe and there is nothing in the literature that should make us overly concerned about dependence or withdrawal. However, there are no long-term safety data and little is known about its safety profile for more than six weeks of use. Unfortunately, many of the patients who complain of insomnia have a chronic condition that lasts from months to years.

Recommendation

Valerian can be recommended as a treatment for insomnia once secondary causes have been ruled out. It may be a desirable alternative to stronger hypnotics, which often produce hangover symptoms, physical dependence, and withdrawal syndrome upon cessation. It can be considered safe for time periods of up to six weeks. Valerian cannot be recommended in pregnant women and should be used with caution in combination with other hypnotic medication. Before starting valerian, all patients should seek advice from their physician.

Ms. Fallek is Research Assistant, Montefiore Medical Center, Bronx, NY. Dr. Milan, Associate Professor of Clinical Medicine Albert Einstein College of Medicine Montefiore Medical Center Bronx, NY, is on the Editorial Advisory Board of Alternative Therapies in Women’s Health.

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