A randomized clinical trial of valerian fails to improve self-reported, polysomnographic, and actigraphic sleep in older women with insomnia

Abstract

Objective

To test the effects of nightly valerian (Valeriana officinalis) extract to improve sleep of older women with insomnia.

Methods

Participants in this phase 2 randomized, double-blind, crossover controlled trial were 16 older women (mean age = 69.4 ± 8.1 years) with insomnia. Participants took 300 mg of concentrated valerian extract or placebo 30 min before bedtime for 2 weeks. Sleep was assessed in the laboratory by self-report and polysomnography (PSG) at baseline and again at the beginning and end of each treatment phase (total of nine nights in the laboratory) and at home by daily sleep logs and actigraphy.

Results

There were no statistically significant differences between valerian and placebo after a single dose or after 2 weeks of nightly dosing on any measure of sleep latency, wake after sleep onset (WASO), sleep efficiency, and self-rated sleep quality. In comparing each treatment to baseline in separate comparisons, WASO significantly increased (+17.7 ± 25.6 min, p = .02) after 2 weeks of nightly valerian, but not after placebo (+6.8 ± 26.4 min, NS). Side effects were minor and did not differ significantly between valerian and placebo.

Conclusion

Valerian did not improve sleep in this sample of older women with insomnia. Findings from this study add to the scientific evidence that does not support use of valerian in the clinical management of insomnia.

Introduction

Older adults commonly experience disturbed sleep with nearly 50% reporting insomnia symptoms of prolonged sleep latency, frequent nocturnal or early morning awakenings with an inability to return to sleep [1], [2]. Polysomnographic (PSG) recordings of sleep in older adults also show frequent awakenings, increased nighttime wakefulness, and reduced slow-wave sleep [3], [4]. Women are more likely than men to report insomnia and this gender difference increases with age [5]. Insomnia is associated with negative health consequences including impaired daytime function, fatigue, reduced quality of life, and increased healthcare utilization [6], [7]. Additionally, insomnia is a risk for major depression [8], and prolonged sleep latency and reduced sleep efficiency are associated with an excess risk of dying after controlling for age, gender, and medical burden [9]. Older adults frequently use prescription hypnotics, sedating anti-depressants, or over-the-counter sedating antihistamines to treat insomnia [10], [11] despite observations that many of these drugs further disrupt sleep and have untoward side effects, e.g., daytime sleepiness, drug tolerance, memory impairments, dry mouth, constipation, and rebound insomnia on withdrawal of the medication [12], [13].

Complementary and alternative medical (CAM) therapies may be useful for management of insomnia in older adults. The 2003 National Sleep Disorders Research Plan recognized as a priority the importance of studies evaluating CAM therapies for sleep disturbances [14]. National surveys indicate that over 50% of middle-aged to older adults use daily dietary supplements, particularly herbal products, and such use is estimated to increase among older adults in the United States over the next few decades [15], [16], [17]. Recent analyses of the 2002 National Health Interview Survey Data revealed that a large number of adults use herbal preparations (including valerian) and behavioral strategies to self-manage their insomnia and believe these strategies are very effective [18], [19]. Despite evidence of widespread interest, research evidence is lacking on the efficacy of many CAM therapies, especially in older adults.

Valerian, derived from the root of the plant Valeriana officinalis, is an herbal supplement that is commonly used as a sleep aid and has been recommended as potentially useful for older adults [20]. Valerian contains a variety of chemical compounds including valerenic acid and derivatives (hydroxyvalerenic acid, acetoxcyvalerenic acid, and valerenal) [21] that may act synergistically to exert sedative effects. Similar to conventional sedative-hypnotic medications, constituents of valerian are believed to activate gamma-aminobutyric acid (GABA) receptors that are involved in sleep promotion and regulation. Constituents of valerian have also been shown through in vitro and animal studies to affect other receptors – adenosine and glutamine (an amino acid that is metabolized into GABA) – involved in regulation of sleep and waking [22], [23], [24], [25], [26].

Few studies have tested the effects of valerian in older adults. In an early double-blind, placebo-controlled randomized clinical trial (RCT) of 150 German elder home residents, a greater proportion of those given valerian for 30 days (compared to placebo) had reduced self-reported sleep disturbance (significance not reported) [27]. In another double-blind, placebo-controlled RCT of 78 elder home residents with sleep disturbance, a significantly greater proportion of individuals given valerian for 14 days compared to placebo self-reported reduced sleep latency and improved sleep maintenance [28]. In an 8-day double-blind, placebo-controlled RCT of 14 older women with insomnia, no significant differences were found between the valerian (n = 8) and placebo (n =6) groups on self-report or PSG sleep onset or maintenance outcomes [29]. These studies tested preparations of V. officinalis that were extracted and concentrated using either water alone [28], [29] or a preparation with a high concentration of valepotriate constituents [27]. Only one double-blind crossover RCT tested an ethanolic valerian extract (similar to the product used in the current study) in 16 older adults [30]. This study reported no significant differences among a single dose of placebo, 300 mg valerian, or 600 mg valerian on self-report, PSG sleep onset or maintenance outcomes. Overall, this mixed evidence is far from conclusive in supporting efficacy for valerian to improve sleep.

The aim of this double-blind, placebo-controlled crossover RCT was to determine whether a single dose or 2 weeks of nightly valerian treatment would improve sleep outcomes in older women reporting insomnia. We hypothesized that valerian administration (compared to placebo) would improve both self-report and PSG measures of sleep. In addition, we used continuous daily actigraphy throughout the trial to ascertain the effect of valerian on sleep/wake patterns when participants were at home. The primary study outcome measures were wake after sleep onset (WASO) and sleep efficiency (SE) from self-report, PSG, and actigraphy; sleep latency (SL) from self-report and PSG; and overall sleep quality (SQ) from self-report only.