Background

The inability to fall asleep (sleep latency), to stay asleep or wake too early before having got enough sleep (sleep duration) is referred to as insomnia. It is a recognized disorder clinically defined as the "difficulty initiating or maintaining sleep or non-restorative sleep".1^(p.1373) It is a common problem affecting the adult population worldwide. In the United States (US), 10% of the adult population is affected by insomnia.1 Europe has about 32,746 million people affected by insomnia, with the highest prevalence in France.2 In a study across seven European countries (Czech Republic, France, Finland, Germany, England, the Netherlands and Italy) and Israel, the prevalence of insomnia was 24% in 2014.2 Eight Health and Demographic Surveillance System sites in Africa and Asia - Agincourt (South Africa), Ifakara (Tanzania), Nairobi (Kenya), Navrongo (Ghana), FilaBavi (Vietnam), Matlab (Bangladesh), Purworejo (Indonesia) and Vadu (India) - reported that 16.6% of adults had nocturnal sleep problems.3 About 10-20% of the adult global population currently uses sleeping pills or tranquilizers to relieve insomnia and other sleep disorders.4

Medications to aid sleeping are often sold over the counter, including antihistamines (e.g. diphenhydramine) or pain pills (e.g. acetaminophen). Since antihistamines can cause lingering grogginess and have anti-cholinergic effects that may be contraindicated in a variety of health conditions, many healthcare providers prescribe sedative-hypnotic drugs or tranquilizers for sleep assistance. The most commonly prescribed drugs through the 1990s were benzodiazepines. Because of many problems associated with benzodiazepines, non-benzodiazepines (e.g. zolpidem and zaleplon) became popular in the early 1990s. Today, zolpidem is the 10th bestselling prescription drug worldwide5 and the top-selling sleeping pill in the US with more than 26.5 million prescriptions written.6

While prescribed sleeping medications can be useful in some cases, their use should be limited, particularly benzodiazepines, which are associated with dependence.7 Non-benzodiazepine hypnotics such as zolpidem have adverse events similar to those of benzodiazepines, especially in older adults and show minimal improvement in sleep latency and duration.10 While newer drugs are thought to cause fewer side effects than their benzodiazepine predecessors, the newer compounds can cause a myriad of serious problems such as confusion, aggression, hallucination, daytime drowsiness and dizziness leading to injury,8 especially when used in combination with other antidepressant medications or alcohol.6

The risk of falls in older adults increases with the number and types of drugs taken, with psychoactive drugs the most commonly reported as increasing fall risk and related injuries.9,10 The use of zolpidem by adults aged 65 years and over was associated with almost two times the risk of fracturing a hip and may be associated with risks similar to those associated with benzodiazepine use in older patients.8 Current clinical guidelines for older adults advocate that non-benzodiazepine hypnotics be limited to short-term use (<90 days) only on a case-by-case basis.10 Providers should refrain from prescribing antihistamines to older adults and educate patients on their lack of proven efficacy and potential for significant adverse effects.10 Any type of benzodiazepines (short and intermediate acting) for treatment of insomnia should be avoided in adults aged over 65 years.10

Since there are prescribed and over-the-counter use of sleeping pills by older adults, especially during hospitalization, with concomitant adverse effects, it is important to identify safer sleep aid regimens or treatments for this population. One such non-pharmacologic sleep aid is lavender essential oil, which can be delivered orally or by aromatherapy.

Aromatherapy is documented as an integrative therapy and tool of holistic nursing and is defined as the therapeutic use of essential oils from plants for the enhancement of physical, emotional and spiritual wellbeing. Aromatherapy is administered through cutaneous (e.g. massage), oral (e.g. pill or tea) or nasal (e.g. electronic diffuser, nasal inhaler and cotton balls infused with oil placed near the head while sleeping or resting) routes.

There are over 200 species of lavender (Lavenula) reported to exist. Its essential oil is produced by steam-distillation of the flowering heads and leaves of the plant. Key active constituents of the oil are linalyl acetate and linalool. The true mode of action of fragrance aromatherapy remains somewhat speculative with effects being attributed to physiologic (amygdala) and psychologic (associations to an aroma) responses.13 Animal studies report a possible sedative effect as linalool acts on gamma aminobutyric acid (GABA) pathways, inhibiting binding of GABA and a depressant effect on neurotransmission.11

Lavandula angustifolia essential oil has anxiolytic properties that may improve sleep and reduce anxiety in animals and humans, without the potential for adverse reactions or side effects of conventional hypnotics and anxiolytics.12-14 Studies have found that inhaled lavender improved sleep duration in benzodiazepine-withdrawing patients,15 hospitalized elderly patients16 and middle-aged women with insomnia.14 Inhaled lavender was also found to improve sleep quality in patients with ischemic heart disease.17 Oral lavender essential oil was found to improve the duration and quality of sleep without causing sedative side effects in patients with subsyndromal anxiety.18

Silexan is an oral, patented active substance produced from the essential oil of L. angustifolia (true lavender) flowers. Dosage ranges from 80 to 160 mg of the Silexan supplement containing approximately 35% linalool and 51% linalyl acetate.12 Silexan has been shown to have a beneficial effect on anxiety and disturbed sleep.14

A search of MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports and the Cochrane Database of Systematic Reviews identified two review articles.19,20 One review included seven studies of Silexan use conducted prior to 2012.19 The studies included in this review compared the use of Silexan to another drug or placebo and conclude that Silexan was more effective than placebo and as effective as lorazepam in patients with anxiety disorders.14 A critical appraisal of the methodological quality of this review revealed no comprehensive, systematic search process to identify studies for inclusion and no appraisal of the methodological quality of the included studies. Another review included 15 randomized trials published prior to 2010 that evaluated the use of any form of lavender aromatherapy preparation on anxiety.20 Seven of the included studies showed some benefit of lavender over the control (placebo, paroxetine or lorazepam) for outcomes measured. No studies were included in these reviews that compared the effects of Silexan with inhaled lavender essential oil aromatherapy.

The current systematic review aims to synthesize the best available evidence on the effectiveness of Silexan oral lavender essential oil compared with inhaled lavender essential oil aromatherapy on sleep latency, sleep duration, sleep quality, disturbed sleep and anxiety in adult patients. Silexan is a new formulation (circa 2010) currently being produced in Germany and researched there and in Europe. It is not readily available worldwide, but inhaled lavender is. If lavender essential oil aromatherapy can be shown to be as effective as Silexan, the use of aromatherapy may be promoted in markets where Silexan is not available to improve sleep an anxiety in adult patients.

Inclusion criteria

Types of participants

The current review will consider studies that include all adult patients, aged 18 years and over, regardless of comorbidities or setting. Studies that include children under the age of 18 years and pregnant and/or lactating women will be excluded.

Type of intervention

The current review will consider studies that evaluate the use of Silexan oral lavender essential oil therapy of any dosage and duration.

Comparator

The current review will consider studies that use inhaled lavender essential oil aromatherapy of any dosage and duration as a comparator.

Outcomes

The current review will consider studies that include the following outcome measures: sleep latency, sleep duration, sleep quality and disturbed sleep as measured by valid and reliable tools measuring sleep disturbance such as the Pittsburgh Sleep Quality Index (PSQI).

The PSQI is a 19-item self-reported questionnaire that evaluates sleep quality over the past month and produces seven sleep components related to sleep routines, including period of sleep, sleep disruption, sleep latency, habitual sleep efficiency, use of sleep medicine, daytime dysfunction due to sleepiness and overall sleep quality.21 Each sleep element produces a score ranging from 0 to 3, with 3 indicating the greatest dysfunction. The sleep element scores are added to give a global sleep quality score, ranging from 0 to 21. The higher the score, the greater the indication of poor sleep quality during the prior month. Based on the literature, a global score of >5 is classified as a poor sleeper and a score of <=5, a good sleeper.

The current review will also consider studies that include the outcome of anxiety as measured by valid and reliable tools such as the State Trait Anxiety Inventory (STAI),22 the Hamilton Anxiety Scale (HAMA)23 or the Becks Anxiety Inventory (BAI).24 The STAI is a commonly used measure of trait and state anxiety. It is a 40-item unidimensional scale that can be used in clinical settings to diagnose anxiety and to distinguish it from depressive syndromes. Half of the items measure situational or state anxiety (STAI-S) and the other half measure underlying or trait anxiety (STAI-T). Responses to STAI-S items indicate intensity of feeling on a 1-4 scale, from "not at all" through "somewhat", "moderately so", to "very much so". The STAI-T items question "how you generally feel" and the response scale indicates frequency: "almost never", "sometimes", "often" and "almost always". The HAMA is a 14-item scale that measures the severity of anxiety symptoms, each defined by a series of symptoms and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild-to-moderate severity and 25-30 moderate-to-severe. The BAI is a 21-item scale, with scores for each item ranging from 0 to 3. Each item is descriptive of subjective, somatic or panic-related symptoms of anxiety. The BAI is a valid and reliable scale that has been found to discriminate well between anxious and non-anxious diagnostic groups in a variety of clinical populations.

Types of studies

The current review will consider both experimental and epidemiological study designs, including randomized controlled trials, quasi-experimental studies, before and after studies, prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies for inclusion. Descriptive and qualitative studies will be excluded from this review.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published between 2010 and the present date will be considered for inclusion in this review, as Silexan is a new formulary that was formulated in 201018 and first appeared in clinical studies in 2010.18,25 This timeframe was selected to capture all studies evaluating the use of Silexan on sleep and anxiety-related sleep disturbances.

The databases to be searched include: PubMed, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE.

The search for unpublished studies will include: ProQuest Dissertations and Thesis and New York Academy of Medicine.

Initial keywords to be used will be: Silexan, lavender oil, sleep, sleep latency, sleep duration, sleep quality, disturbed sleep and anxiety.

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.

Data extraction

Data will be extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Reviewers will attempt to contact study authors to seek missing data or provide clarity in reported results.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Appendix I: Appraisal instruments

MAStARI appraisal instrument

Appendix II: Data extraction instruments

MAStARI data extraction instrument

References