Valerian Root for Insomnia
By Susan T. Marcolina, MD
Although Sleepless in Seattle was a romantic comedy, insomnia is neither a laughing nor a romantic matter. Insomnia is the most commonly reported sleep problem in industrialized nations worldwide; women and elderly persons are at increased risk.1 The sequelae of insomnia include diminished productivity and increased susceptibility to accidents from poor concentration, fatigue, and cognitive dysfunction.
Valerian is one of the most well-known soporific herbal therapies, specifically the valerian root extract (VRE). The European variant, Valeriana officinalis, is most commonly used and referred to in the scientific literature, although there are more than 250 identified species of this genus. The first reference to the sedative, hypnotic properties of valerian is attributed to the ancient Greek physician and pharmacist Galen (129-199 AD).2
Medical Etiologies
To relieve secondary insomnia, psychiatric and medical disorders responsible for it must be effectively treated. Table 1 outlines these disorders. Treatment also should include patient implementation of appropriate sleep hygiene practices (see Table 2). For persistent symptoms, short-term pharmacotherapy may be necessary.
Although pharmacotherapy for primary insomnia is effective, significant side effects occur. Patients complain of daytime sedation or hangover. Dependence may develop with continual use and the possibility exists of fatal overdose if taken in combination with alcohol or drugs. Thus many patients, in search of symptomatic relief, seek alternative, seemingly safer, natural options in the form of herbal therapies.
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Table 1 |
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Causes of secondary insomnia |
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• Medical • Psychiatric • Delirium (e.g., sepsis- or medication-induced) • Mood disorders • Pain syndromes • Anxiety disorders • Endocrinopathies (e.g., hyperthyroidism) • Schizophrenias • Cardiac dysfunction (e.g., CHF, angina) • Substance dependence/abuse • Sleep apnea syndrome (central, obstructive) • Dementia
• Side effects of medications (e.g., theophylline, • Chronic obstructive lung disease • Restless leg syndrome/periodic limb movements in sleep • Gastroesophageal reflux |
| Adapted from: Davidson JRT, Connor KM. Herbs for the Mind. New York: The Guilford Press; 2000. |
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Table 2 |
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Recommendations for sleep hygiene |
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• Maintain a regular sleep/wake schedule • Institute a program of daily exercise
• Insulate bedroom from excessive light, noise, heat, • Avoid heavy exercise before bedtime • Avoid large meals before bed • Avoid daytime napping • Avoid long-term use of prescription or OTC sleep medicines • Avoid tobacco, caffeine, and alcohol prior to bedtime Adapted from: Davidson JRT, Connor KM. Herbs for the Mind. New York: The Guilford Press; 2000. |
Pharmacology
Valerian is a perennial herb native to Europe and temperate zones of Asia. The root and rhizome of this plant are used for medicinal preparations. Its chemical composition varies significantly from one species to the next and within plants of the same species. Differences in growing conditions, root age, harvesting times, and drying techniques also affect chemical composition.
Constituents
In the early 1900s, scientists isolated the essential oil from the rootstock and have since identified more than 150 constituents. The sesquiterpene valeneric acid is an important component of the essential oil, demonstrating substantial sedative and antispasmodic activity. However, it does not fully account for the sedative effects of the root; instead, synergism between the individual chemical constituents probably does. The valepotriate iridoids that compose between 0.2% and 2% of the root are fatty acid esters that have shown some calming activity in animal studies. Alkaloids, such as actinidine, valerianine, and alpha-methylpyrrylketone, are also major constituents of the root, but exist in small amounts and do not contribute to the sedative properties.
Valerenic acid appears to inhibit the enzyme system responsible for the breakdown of gamma-aminobutyric acid (GABA), thereby increasing GABA concentrations and decreasing CNS activity. The valerian root also contains other compounds, such as lignans and GABA, which may account for its sedative properties.2,3
Animal Studies
Bos et al found a direct relationship between the valepotriate content of valerian and toxicity of VRE in animal studies. This effect was greatest in species of Valeria such as Valeriana edulis, which contains the highest level of valepotriates; Valeriana officinalis was found to be the least toxic in this regard. Aqueous extractions of valerian contain no valepotriates.4
Clinical Studies
Different clinical studies evaluating the efficacy of valerian for insomnia are difficult to compare because different preparations of valerian are used, the numbers of patients are small, validated outcome measures are few, or pre-bedtime variables are poorly controlled. Nevertheless, some information from several studies appears important.
A multicenter, double-blind, randomized study conducted by Vorbach et al randomized 121 patients with non-organic insomnia to receive an alcoholic valerian extract (LI 156) (600 mg/d) or indistinguishable placebo daily for 28 days.5 Patients were not taking any medications that would interfere with sleep. Sleep efficacy was assessed with four validated rating scales. Patients taking valerian had significantly better results than did those taking placebo on the clinical global impression scale after 14 days and on all additional measures of sleep and mood after 28 days. Two patients from the placebo group and two from the valerian group reported adverse events. Those adverse effects from valerian included headache and next-morning drowsiness.
Leathwood et al compared the effects of 400 mg of a dry 3:1 aqueous extract of valerian root to placebo and a commercial preparation (Hova) that contained 60 mg valerian and 30 mg hop flower extract in 128 participants (some with and some without sleep problems).6 Each volunteer tested nine samples (three placebo, three valerian, three Hova) presented in a random order and taken 1 hour before bedtime on non-consecutive nights. All participants were instructed to avoid food intake, alcohol, or exercise on the test nights and effects were measured by a questionnaire the following morning. Sleep latency and quality were rated as significantly improved with valerian compared to placebo, particularly by those participants who were poor sleepers. Compared to valerian or placebo, increased drowsiness and nausea were reported with Hova.
Donath et al performed a randomized, double-blind, placebo-controlled, crossover study involving 16 patients (12 female, median age 49 years) with previously established insomnia.7 The two inclusion criteria were a diagnosis of primary insomnia and the absence of acute illnesses. The patients underwent eight poly-somnographic recordings at baseline, 1, 2, and 4 weeks for placebo and valerian. After a single dose of valerian, no effects on sleep structure and subjective sleep assessment were observed. After multiple-dose treatment, sleep efficiency showed a significant increase for valerian and placebo in comparison to baseline polysomno-graphy. However, compared to placebo, valerian reduced slow-wave sleep latency (21.3 minutes vs. 13.5 minutes, respectively, P < 0.05). The study showed low numbers of adverse events during the valerian treatment periods (three vs. 18 in the placebo period). The authors concluded that treatment with a valerian extract demonstrated positive effects on the sleep structure and sleep perception of insomnia patients.
Kuhlmann et al examined the influence of valerian treatment on reaction time, alertness, and concentration in healthy persons.8 This randomized controlled, double-blind trial enrolled 102 male and female volunteers. The effect initially was examined the morning after a single evening dose of valerian root extract (600 mg), flunitrazepam (1 mg), or placebo, and then after two weeks of evening administration of valerian or placebo. The primary outcome criterion was reaction time, measured with the Vienna Determination Test. Secondary criteria included an alertness test, a tracking test, sleep quality, and safety criteria.
The single administration of valerian did not impair reaction times, concentration, and coordination of study participants compared to placebo. Flunitrazepam caused deterioration in these measured outcomes compared to placebo. Results after 14 days confirmed that there were no statistical differences between valerian and placebo for reaction times and other psychometric testing results. There was a trend toward improved sleep quality for valerian compared to placebo that did not reach statistical significance. Valerian and placebo were not statistically different with regard to adverse effects.
Adverse Effects
Acute side effects may include mild headaches, nausea, nervousness, palpitations, and morning drowsiness. Although most reports describe a lack of residual morning effects on alertness and concentration, some suggest that impaired alertness and information processing does occur. This impairment is dose-dependent and peaks within the first few hours after an oral valerian dose. Therefore, patients should be cautioned against driving or operating dangerous machinery within the first several hours after ingestion.
Several cases of hepatotoxicity involving long-term use of single-ingredient valerian preparations have been reported. Since a variety of dosages were used in the reported cases and higher doses have been safely used, these hepatotoxic reactions may have been idiosyncratic.9 In addition, Garges reported a case of a patient who had taken VRE for years when he was admitted to the hospital for coronary artery bypass graft surgery. VRE was abruptly discontinued, resulting in a withdrawal syndrome which responded to intravenously administered midazolam, which was gradually tapered.10
There is insufficient data to determine the efficacy and safety of VRE in children younger than 18 years of age and in pregnant women; valerian should not be used in these populations.
Drug Interactions
Valerian can potentiate the sedative action of alcohol and other sedative drugs. There is evidence that valerian can inhibit the cytochrome P450 3A4 enzyme; it may increase levels of drugs such as lovastatin, ketoconazole, fexofenadine, etoposide, paclitaxel, vinblastine, and vincristine, which are metabolized by this pathway.11
Dosage
In controlled trials of healthy subjects and in patients with sleep disturbances, doses of VRE ranging from 300 to 900 mg were shown to be helpful in promoting sleep, although dosing has not been studied systematically.3,12
Formulation
Most pharmacopeia standards recommend that single-ingredient valerian extracts be standardized to at least 0.5% valerenic acid. Valerian products should be stored in closed containers and protected from light and moisture. While valerenic acid and its breakdown products are fairly stable, these and other components of the essential oil degrade over time and in the powdered root form, can degrade by as much as 50% in six months. The valepotriate constituents of VRE are unstable, water insoluble, and susceptible to degradation with temperatures higher than 40° C, humidity, and acid or alkaline exposure.2
Regulation
The German Commission E has approved several fixed combinations of VRE and other herbs, includ- ing passionflower, chamomile, lemon balm, and hops; however, systematic studies documenting efficacy are lacking.13
Conclusion
Standardized potency VRE can be effective for many patients with chronic primary insomnia. Studies have shown an improvement in sleep latency and global functioning (as assessed by validated questionnaires), without significant hangover effects seen with traditionally used sedative hypnotics. One study suggests the possibility of a withdrawal syndrome similar to benzodiazepine withdrawal with abrupt discontinuation. Several case reports have documented hepatic toxicity after long-term usage; therefore, clinical use for individual patients should be limited to 2-6 weeks.
Recommendation
The diagnosis of insomnia requires a careful work-up to determine secondary medical or psychiatric diagnoses. Standardized VRE can be a treatment option for some nonpregnant patients older than age 18 with chronic primary insomnia for 2-6 weeks in conjunction with sleep hygiene measures.
Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA.
References
1. Chesson AJ, et al. Practice parameters for the evaluation of chronic insomnia. Sleep 2000;23:5.
2. Davidson JRT, Connor KM. Herbs for the Mind. New York: Guilford Press; 2000.
3. Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol 1999;51: 505-512.
4. Bos R, et al. Cytotoxic potential of valerian constituents and valerian tinctures. Phytomedicine 1998;5:219-225.
5. Vorbach EU, et al. Therapie von Insomnien. Wirksamkeit und Vertraglichkeit eines Baldrianpreparats. Psychopharmakotherapie 1996;3:109-115.
6. Leathwood PD, et al. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 1982;17:65-71.
7. Donath F. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000;33:47-53.
8. Kuhlmann J. The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers. Pharmacopsychiatry 1999;32:235-241.
9. Klepser TB, Klepser ME. Unsafe and potentially safe herbal remedies. Am J Health Syst Pharm 1999;56: 125-138.
10. Garges HP, et al. Cardiac complications and delirium associated with valerian root withdrawal. JAMA 1998;280:1566-1567.
11. Budzinski JW, et al. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000; 7:273-282.
12. Stevinson C, Ernst E. Valerian for insomnia: A systematic review of randomized clinical trials. Sleep Med 2000;1:91-99.
13. Blumenthal, M, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Dallas, TX: American Botanical Council; 1998.
Marcolina ST. Valerian root for insomnia. Altern Med Alert 2002;5:77-80.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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