Systematic literature review with meta-analysis on essential oil interventions for agitated behavior in dementia patients

Search strategy

The literature search was carried out on six databases: PubMed, Taylor & Francis, EBSCO, Cochrane, ScienceDirect, and ProQuest from 2002 until October 2023. The literature search was done with keywords using boolean operators, as detailed in Table 1.

Study eligibility criteria

The inclusion criteria of this meta-analysis refer to the PICO framework in Table 2. Inclusion and exclusion criteria were predefined before the literature search to ensure the specificity and homogeneity of the results. The inclusion criteria were 1) data available or accessible in the English language, 2) studies that involve patients previously diagnosed with dementia with present agitation symptoms as their sample, 3) randomized-controlled trial (RCT) studies, and 4) studies that include at least one parameter analyzed in this study, namely: Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), and Quality of Life (QoL). The exclusion criteria were 1) non-human sampling studies, 2) non-peer-reviewed studies, and 3) journals not accessible for free through online databases. The authors individually evaluated the eligibility of each study, and any disagreement was solved through discussion.

Outcome of interest

This paper analyzes four outcome parameters to determine the efficacy of essential oil interventions in managing agitation symptoms in BPSD patients. The survival risk for BPSD patients following essential oil intervention was analyzed and compared to the control group. Agitation was evaluated through CMAI and NPI. CMAI is a structured assessment of agitation among individuals with dementia, primarily designed for application in long-term care facilities. CMAI consists of 29 agitated behavior rating questionnaires, each rated on a 7-point frequency scale. A total CMAI score is obtained by summing all the individual items, ranging from 29 to 203. A total score of >45 is usually regarded as clinically significant agitation (Panca et al., 2019). NPI evaluates behavioral symptoms in dementia across 12 domains, including agitation, using frequency and severity ratings. Each domain scores from 0 to 12, and a score of ≥4 in any domain is considered clinically significant (Panca et al., 2019; Musa et al., 2017). In addition, this study assessed patients’ QoL following the implementation of essential oil interventions to determine their applicability. Fourteen authors independently extracted the outcomes from the included papers to be used for quantitative analysis, and any disagreements were resolved through discussion.

Data collection and analysis for extraction

Data collection in this study followed the PRISMA flowchart, including identifying studies in the database, screening for duplicates, titles, and abstracts; assessing full-text eligibility; and extracting and analyzing included studies. We manually pulled studies from the extraction tabulation. The extracted data were (1) Author and year of publication, (2) Age, (3) Disease, (4) Number of patients, (5) Genders, (6) Type of intervention, (7) Number of patients in intervention, (8) Number of patients in control, and (9) Follow-up period. The main finding of this study was to assess the efficacy of essential oils in BPSD patients. Efficacy was defined as improving the NPI, CMAI, and QoL.

Quality appraisal

The risk of bias assessment of RCT studies was assessed using The Revised Tool for Risk of Bias in Randomized Trials (RoB 2.0) (Sterne et al., 2019). Afterward, the results were inputted into the “bias” section of the spreadsheet. The spreadsheet was then uploaded to the ROBVIS website to display the assessment result using the traffic light system effectively.

Quantitative analysis of meta-analysis

Meta-analysis was performed using Review Manager ver. 5.4 (The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen) (RevMan, 2020). The survival risk analysis of essential oil was evaluated as dichotomous data. Meanwhile, CMAI, NPI, and QoL were assessed as continuous data with a 95% confidence interval (CI). The inverse variance model served as the statistical method, while the fixed or random effect models were used based on the heterogeneity of each outcome. I² statistics will analyze heterogeneity, with cut-off criteria of 0%, 25%, 50%, and 75% corresponding to insignificant, low, moderate, and high heterogeneity.

Study selection and identification

Following the elimination of duplicate studies and abstract screening, 15 RCTs underwent a comprehensive evaluation. Ultimately, 11 RCTs were chosen for inclusion in the meta-analysis, as depicted in Figure 1. The exclusion of four RCTs was necessitated due to incomplete outcome data, and two of these excluded trials needed a control group for comparison.

Figure 1. PRISMA flowchart for literature search.

Summaries of the included studies

The characteristics of each study were examined and are listed in the extended data: Appendix 1 (Taslim et al., 2024).

Quality appraisal

The final included RCTs were assessed for quality using the Cochrane RoB 2.0. Out of the 11 RCTs included, it is essential to note that three studies displayed a high risk of bias, primarily due to issues related to incomplete outcome data. On the other hand, most studies displayed a low risk of bias across all the domains examined (Figure 2).

Figure 2. The Revised Tool for Risk of Bias in Randomized Trials (RoB 2.0) of 11 randomized-controlled trials (RCTs) studies.

Meta-analysis of survival risk in essential oil interventions versus control

In the binary meta-analysis comparing the efficacy of several essential oils in dementia agitation treatment, the results of the random effect meta-analysis depicted in Figure 3 show that dementia patients treated with essential oils have a survival risk of 0.63 times better compared with control treatment (odds ratio [OR] = 0.63; 95% CI: 0.41, 0.98; p = 0.04). The heterogeneity among the studies was moderately high and significant (I² = 74%). Thus, the Random Effect Model approach calculates the overall effect estimation. Additionally, the symmetrical pattern observed in the funnel plot of the studies included in the meta-analysis suggests the absence of publication bias (Figure 4).

Figure 3. Meta-analysis of the survival risk in essential oil interventions versus control.

Figure 4. Funnel plot of included studies.

Meta-analysis of the post-intervention NPI, CMAI, and QoL Score in essential oil interventions versus control

As depicted in Figure 5, the results show a significant improvement in NPI after administering essential oil interventions (standardized mean difference [SMD] = -2.97; 95% CI = -5.61, -0.32; p = 0.03; I² = 98%). Nevertheless, in the case of the CMAI, it is essential to highlight that there has been no discernible and statistically significant improvement observed following the administration of essential oil interventions (SMD = 0.17; 95% CI = 0.37, 0.71; p = 0.53; I² = 74%). QoL assessment showed a trend of favoring the control group following the implementation of essential oil interventions (SMD = 0.38; 95% CI = -1.22, 1.98; p = 0.64; I² = 93%).

Figure 5. Meta-analysis of the post-intervention NPI, CMAI, and QoL score in essential oil interventions versus control.

Effects of essential oil interventions in patients’ survival risk

The efficacy of essential oil interventions was assessed using a binary meta-analysis to calculate patients’ survival risk compared to control treatment. In eleven RCTs, the survival risk was found to favor the efficacy of the essential oil. The findings of this study indicate that essential oil interventions result in statistically significant survival risk enhancements with moderate heterogeneity.

A study by Lin et al. in 2007 showed aromatherapy with Lavandula angustifolia was noted for its safety and resulted in a significant improvement in agitation of dementias. The safety, marked by no sequential effect occurring, was consistent with the chemical property of essential oils that the molecules would pass out from the body after 24 hours. This is also supported by a study from O’Connor et al. in 2013 using the same essential oil ingredient and Watson et al. in 2019 using the combination of Lavandula angustifolia and Melissa officinalis’ oil. In Akhondzadeh et al., 2003 also showed a higher frequency of agitation coupled with higher survival risk in patients treated with a placebo compared to Melissa officinalis oil. It is important to consider that this oil may also have an effect in reducing cognitive impairment and, therefore potential to be developed in the management of Alzheimer's patients.

Effects of essential oil Interventions in agitation behavior measurements

Agitation behavior was assessed using two tools, the CMAI and NPI. In four RCTs, the CMAI was used to determine the frequency of agitation among individuals with dementia. Simultaneously, another four RCTs used the NPI to examine a broader spectrum of behavioral symptoms related to dementia, spanning 12 domains, including the assessment of agitation. The findings of this study indicate that essential oil interventions did not result in any notable and statistically significant CMAI score enhancements. The insignificant effect found in the CMAI assessment may be attributed to variations in how the intervention was administered. Specifically, two studies applied the essential oil through inhalant aromatherapy, while another pair of studies applied the intervention using topically derived essential oils.

In contrast, there was a significant improvement in NPI scores after using essential oils. These results imply potential impacts on another 11 domains of NPI, including hallucinations, delusions, depression, anxiety, disinhibition, joy, apathy, irritability, aberrant motor behavior, night-time behavior, or appetite changes. It is noteworthy that Lin et al. (2007) reported a significant decrease in agitation, irritability, aberrant motor behavior, and night-time behavior following the administration of lavender aromatherapy. Another study by Fujii et al. (2008) found that the essential oil group's NPI assessment was significantly improved compared to the control group, which showed no significant change. However, contradicting results were found in Burns et al. (2011), which showed no specific benefit for aromatherapy in the treatment of agitated behavior, assessed across a 12-week treatment duration.

Effects of essential oil interventions on quality of life (QoL)

Patients’ QoL is mainly affected by disturbances of behavior, mood, thought content, and perception (Scuteri et al., 2019). Thus, evaluating the patients’ QoL is crucial for future implementations of essential oil interventions. BPSD patients often require long-term care, and the effectiveness of interventions in improving their quality of life is vital for ensuring patients’ treatment adherence. This study reveals the QoL through two studies, resulting in a trend that favors neither the intervention nor the control group with insignificant p-value reported. However, the included studies are considered as high in heterogeneity. This happened due to the difference in the essential oil's main ingredients and application mechanism. The first study by Leach et al. (2021) focused on applying only topical creams and/or oils without a clear explanation regarding the ingredients used. The other study from Burns et al. (2011) used Melissa officinalis as the main ingredient of the essential oil coupled with massage techniques to help alleviate agitation.

Although the meta-analysis is not statistically significant, the individual reports from each study show a promising effect of essential oil on agitation. Leach et al. (2021) found a marginally significant result in improving BPSD patients’ QoL following the ten weeks of essential oil interventions. However, it has been demonstrated that essential oil interventions lead to a more rapid improvement in QoL compared to the control group during the initial four and eight weeks of follow-up. In the control group, QoL progressively improves over time until it reaches a similar level as that achieved by the essential oil interventions in the tenth week. Another study by Burns et al. (2011) shows that at weeks four and twelve, there were no discernible differences between aromatherapy, donepezil, and placebo. Nonetheless, all three groups had notable improvements, with the NPI improving by 37% throughout the course of the 12-week study.

From outside the study included in the analysis, essential oil also shows notable effects in alleviating behavioral symptoms that arise from BPSD. In a different investigation conducted by Ballard et al. (2002), noteworthy enhancements in the patients’ QoL were observed following four weeks of 10% Melissa essential oil topical application, specifically in a substantial reduction of social withdrawal behaviors and a significant increase in engaging in constructive activities. Additionally, a systematic review by Li et al. (2021) reported the favorable effects of aromatherapy in multiple studies, such as enhancements in their functional abilities, heightened alertness, improved communication, increased interest in patients’ surroundings, and elevated feelings of enjoyment and relaxation. Therefore, these collective outcomes significantly contribute to improving QoL for BPSD patients. Despite the significant result, the study on QoL assessment has not conclusively established the superiority of essential oils over the control intervention. Therefore, further investigations involving a more significant number of studies are required.

The neurobiological pathophysiology of agitated behavior in dementia

The neurobiological pathophysiological mechanism underlying agitation is associated with the various dysregulation of neurotransmitters. Dopamine, norepinephrine, glutamate, and acetylcholine are released excessively, along with the overactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Meanwhile, there could be a reduction in gamma-aminobutyric acid (GABA) and serotonin levels, both of which play a role in the top-down control of limbic activation (Miller et al., 2020).

At the subcortical level, the prefrontal cortex (PFC) may function appropriately. Proper functioning of the PFC, particularly in tasks involving working memory and executive functions, depends on maintaining optimal norepinephrine levels. Among the three families of noradrenergic receptors (α1, α2, and β), norepinephrine exhibits the strongest affinity for α2 receptors, mainly the α2A subtype found abundantly in the PFC. In situations with low stress levels, α2 receptors are primarily activated, enabling effective PFC functioning, which includes regulating limbic activity. However, as stress levels increase and more norepinephrine is released, α1 and β receptors become engaged, potentially reducing the individual's capacity to think and evaluate various behavioral choices, which may lead to aggressive or agitated behavior (Miller et al., 2020).

Another abnormal reactivity may be found in other frontal lobe areas, such as the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC). The efficient coupling of these higher cortical areas is significant for the involvement of inhibitory control (Miller et al., 2020). They allow for rational risk-reward assessments and calibration of behavior based on social cues before reacting to stimuli. The reduction of noradrenergic neurons in the locus coeruleus, which primarily project to the OFC and ACC, originates the upregulation of adrenergic receptors in the frontal lobe. This leads to the elevated sensitivity to noradrenergic signaling, thus manifesting the agitated behavior in dementia patients (Carrarini et al., 2021).

The amygdala contains adrenoreceptors and dopamine D2 receptors, and it receives direct inputs of dopamine from the ventral tegmental area (VTA) and norepinephrine from the locus coeruleus. Elevating these catecholamines can heighten amygdala activity, thus intensifying conditioned fear responses and paranoia (Miller et al., 2020).

Aggressive behavior is also associated with dysfunctional fronto-limbic emotion regulation circuits. Recent findings suggest serotonin as a primary neurotransmitter for prefrontal amygdala control. Serotonin is a predominantly inhibitory neurotransmitter, and its low levels have been demonstrated in individuals with aggressive personality traits and in those who have attempted suicide by violent means (Miller et al., 2020; Klasen et al., 2019; da Cunha-Bang and Knudsen, 2021).

Moreover, reduced blood flow in the anterior temporal lobe (ATL), the dorsolateral prefrontal cortex (dlPFC), and the superior parietal cortex (SPC) are believed to play a role in generating heightened emotional reactions to external stimuli, potentially leading to the manifestation of aggressive or agitated behaviors (Carrarini et al., 2021).

The mechanism of action of drugs used in agitated behavior management

First and second-generation antipsychotic drugs (APG1 and APG2)

Most treatment guidelines suggest the administration of intramuscular AP drugs, either the first generation (APG1) or second generation (APG2), on severely agitated dementia patients during emergencies (Sadock, 2015). However, the recently published European Academy of Neurology (EAN) guideline advises that treatment using APG2 can proceed only when non-pharmacological approaches prove ineffective (Carrarini et al., 2021; Masopust et al., 2018). This statement underscores the urgency for the advancements of non-pharmacological methods. Therefore, exploring the potential of essential oil intervention as one of the non-pharmacological approaches to achieve similar effects to those of AP drugs may offer a promising alternative.

All AP drugs mainly work by reducing the dopaminergic neurotransmission. The APG1 blocks the D2 dopamine receptors in the brain to inhibit dopaminergic neurotransmission. They also have several other actions, such as antiadrenergic effects by blocking α-1 adrenergic receptors, anticholinergic effects by blocking M1 receptors, and antihistaminergic results by blocking H1 receptors. The APG2 works by blocking D2 dopamine receptors and serotonin receptors, specifically the 5-HT2A receptors. The APG2 also differs from the APG1 by its ‘loose’ binding to the D2, which leads to the rapid dissociation of APG2 to D2 receptors. This often leads to lower EPS side effects caused by the insufficiency of dopamine in the nigrostriatal pathway. Several APG2 also exhibit 5-HT1A agonism, increasing dopamine release in the prefrontal cortex and reducing glutamate release (Stahl, 2021; Grinchii and Dremencov, 2020; Calsolaro et al., 2019).

When focusing on the mechanism of agitated behavior modulation, the relief of behavioral excitability, such as agitation, aggression, and hyperactivity, can be attributed to the targeted D2 receptor blockade within cortico-limbic regions, as demonstrated in the dopamine pathways theory (Ohno et al. 2019; Stahl, 2021). Additionally, the reduction of noradrenergic effects in the OFC and ACC can decrease abnormal reactivity to subtle stimuli (Carrarini et al. 2021).

Benzodiazepines

The primary treatment for agitation of uncertain origin is benzodiazepines. Benzodiazepines act as GABA-A receptor agonists, facilitating inhibitory control from the cortex to the limbic system. GABA, the primary inhibitory neurotransmitter in the central nervous system, plays a crucial role in modulating brain function. Agitated states can compromise the GABAergic inhibitory pathways connecting the prefrontal cortex with the amygdala, leading to inflexible behavioral and emotional responses (Miller et al., 2020). An animal study by Jager et al. (2020) aimed to explore the molecular mechanisms behind aggressive behavior in the BALB/cJ mouse model reveals that the aggressive behavior was linked to reduced GABA levels in the ACC (Jager et al., 2020).

Beta-blockers

Beta-blockers inhibit binding the circulating neurotransmitters catecholamines norepinephrine and epinephrine to adrenoreceptors. Efforts to reduce autonomic arousal and the resulting behavioral manifestations can involve anti-adrenergic medications, such as propranolol, a non-receptor-specific beta-blocker. The lipophilic nature of certain beta-blockers allows them to permeate the blood-brain barrier. The mechanism of action in which beta-blockers influence aggression remains unclear. Potential explanations include inducing mild sedation or diminishing adrenergic activity, either centrally or peripherally, which reduces catecholaminergic responses to stressful situations. Beta-blockers are well-received by individuals with aggression stemming from traumatic brain injuries. Additionally, beta-blockers seem to exhibit effectiveness in mitigating aggression in patients with diverse neuropsychiatric disorders like schizophrenia, dementia, or behavioral issues (Cojocariu et al., 2021; Miller et al., 2020; Molero et al., 2023).

Molecular characteristics of essential oils

Two of the most frequently used essential oils that have shown the greatest efficacy among all are Melissa officinalis L. and Lavandula angustifolia. Melissa officinalis L. has been used to treat nervous system diseases, cognitive dysfunction, and sedation (Ghaffariyan et al., 2012). The active component consists of geranial (65.4 %), geranyl acetate (7.4), neral (24.7 %), (Z)-carveol (0.1%), linalool (0.8%), myrtenol (0.1%), farnesene (0.1 %), 2,3-dehydro-1,8-cineole (0.1 %), and caryophyllene (0.8%) (Chung et al., 2010). It also presents antioxidant activity by the presence of phenolic acids, mainly hydroxycinnamic acid derivatives, for example, rosmarinic acid (RA).

In human intestinal epithelial Caco-2 cell monolayers, RA shows little affinity for the intestinal monocarboxylic acid transporter. The process of paracellular diffusion allows RA to be absorbed since ester groups interfere with MCT connections (Shakeri et al., 2016). The gut microbiota converts most of the retinoic acid (RA) into hydroxylated phenylpropionic acids and m-coumaric acid. MCT then distributes and transports these metabolites throughout the body. RA is also metabolized along with methyl-RA, caffeic acid, and ferulic acid. Plasma and urine contain RA and its metabolites, mostly in conjugated forms like glucuronide or sulfate.

Other factors like food intake, disease conditions, medications, and dietary phenolics can also affect how well RA is metabolized. Co-administration of RA with flavonoids such as luteolin and apigenin (two components available in M. officinalis) can increase the bioavailability of RA in Caco-2 cell monolayers (Shakeri et al., 2016).

Lavandula angustifolia (lavender) has some notable dominant components, which are caryophyllene (24.12 %), terpinen-4-ol (9.57 %), β-phellandrene (16 %), and eucalyptol (15.69%) (Jianu et al., 2013). Its ability to bind to the NMDA receptor was assessed using the competitive antagonist CGP39653 binding assay, now the preferred ligand for labeling NMDA receptors. Neurochemically speaking, NMDA receptors are categorized as ionotropic glutamate receptors (iGLURs) and are implicated in a number of neurological and psychiatric conditions, including Parkinsonism, epilepsy, and damage from prolonged seizures.

Because LEO was able to displace CGP39653 binding in a dose-dependent manner, it is plausible that this oil may calm nerves via modifying NMDA receptors. The anti-agitation qualities of these products that have been observed in animals and some clinical investigations may be explained by this feature. Since glutamate's activation of the NMDA receptor is also linked to neurotoxicity, it may provide neuroprotection by blocking this ionotropic receptor (López et al., 2017).

The possible essential oil interventions mechanism of action

The exact mode of action of essential oils and aromatic herbs is still unknown. Its psychological consequences, however, have been researched. The aromatic molecules for each distinct smell bind specific acceptors on the olfactory epithelium. The olfactory nerve system transmits this stimulation to the amygdala, hippocampus, and limbic system before arriving at the hypothalamus and causing the release of neuromodulators. This results in neurofibrillary tangles (NFTs) in the entorhinal cortex and cognitive impairment typical of dementia (Jimbo et al., 2009). Additionally, this implies a connection between smell and dementia, further supported by demented individuals frequently experiencing defective smell (Gold et al., 2000). Aromatherapy is thought to encourage neurogenesis in the dentate gyrus of the hippocampal region.

Melissa officinalis mechanism of action

As well as having soothing and carminative effects, it has anxiolytic and sedative/hypnotic actions. It has been reported that Melissa officinalis has acetylcholine receptor activity in the central nervous system (Figure 6), with both nicotinic and muscarinic binding properties (Akhondzaheh et al., 2003). Melissa officinalis L. uses the GABAergic system to influence mood and have anxiolytic effects. Recently, a preliminary screening of conventional anxiolytic plant extracts was conducted to investigate this suggested mechanism. This has anxiolytic-like effects because it inhibits GABA-T activity (Ibarra et al., 2010). However, when taken in excess, it dramatically increases anxiety and depressive symptoms, as shown in studies on the effects of rosmarinic acid on mice's behavior under stress and in a clinical trial on Melissa officinalis L.'s anxiolytic effects during stress (Pereira et al., 2005; Kennedy et al., 2002).

Figure 6. Anti-cholinesterases Mechanism of Action in Alzheimer's Disease (AD) by EO.

According to reports, the HPA axis controls these measurements, and GABA levels are assumed to act as a mediator of inhibition (Foley and Kirschbaum, 2010; Cullinan et al., 2008). Consequently, depending on relative stress-induced HPA axis responses, a slight increase in GABAergic activity brought on by chronic Melissa officinalis L. extract ingestion may be sufficient to dramatically lower mild anxiety levels. Still, it may need to be more effective in more stressful settings.

Lavandula angustifolia mechanism of action

The effect of lavender on lipopolysaccharide-induced inflammatory reaction in human monocyte THP-1 cells may be related to HSP70 expression. There have been reports of antioxidant and comparatively mild cholinergic inhibition for linalool and lavender (Huang et al., 2012). At the neuromuscular junction, linalose modifies ion channel activity and inhibits the release of acetylcholine (Figure 5). These results suggest that lavender may have numerous therapeutic targets for Alzheimer's disease, including anticholinergic, neuroprotective, and antioxidant properties. It has been proposed that the antioxidant properties of lavender oil are responsible for its neuroprotective properties against brain ischemia/reperfusion injury (Huang et al., 2012).

Since glutamate-induced NMDA-receptor activation is also linked to neurotoxicity, the essential oil may have neuroprotective effects by blocking this ionotropic receptor. When lavender was given with imipramine, anticholinergic imipramine side effects, such as dry mouth and urine retention, were less common than with imipramine alone. These findings imply that lavender, when used with imipramine, is an efficacious adjuvant medication that improves depression symptoms more quickly (Scuteri et al., 2019).

Benefits and implications of essential oil interventions

Since the 1980s, there has been an increasing trend in scientific research related to essential oils (Scuteri et al., 2017). This remarkable trend has not only expanded medical knowledge. Still, it has also paved the way for a deeper understanding of the mechanisms of essential oil interventions and their prospective implications for future healthcare management.

The initial approach to treating BPSD involves the short-term use of atypical AP agents, typically throughout 6 to 12 weeks. Atypical AP should be closely monitored and combined with nonpharmacological interventions (Scuteri et al., 2017). Research supports essential oil interventions d as an effective non-pharmaceutical treatment option (Takahashi et al., 2020; Leach et al., 2021; Akhondzadeh et al., 2003; Yang et al., 2016). Essential oils, abundant in leaves, seeds, flowers, barks, and rhizomes, consist of numerous lipophilic and low molecular mass constituents that can permeate cell membranes and the blood-brain barrier (Maggio et al., 2016). Essential oils are typically obtained through cold pressing and hydro-distillation (Benny and Thomas, 2019).

Stimulating the olfactory senses is a minimally invasive and efficient procedure (Takahashi et al., 2020). This approach operates through the olfactory bulb, which transmits signals to the hippocampus, a brain region intricately linked to learning and memory functions. This connection between volatile compounds and the hippocampus offers a means to manage the advancement of agitated behaviors in patients with BPSD (Maggio et al., 2016). Through essential oil interventions, olfactory stimulation can be accomplished via systemic absorption, direct or inhalation after topical application. The distribution of pharmacologically active components in the phytocomplex is critical to the effectiveness of aromatherapy in controlling BPSD (Scuteri et al. 2017). Alternatively, a simple approach involves placing fragrances into the patient's environment, which is effective in suppressing the progress of BPSD (Takahashi et al., 2020).

Non-pharmacological interventions continue to hold a crucial consideration, particularly as the principles of the recovery model. This model places significant emphasis on empowering patients, fostering a sense of autonomy, and promoting collaborative decision-making regarding their care, even when patients exhibit aggressive or agitated behaviors (Miller et al., 2020). Cultivating a therapeutic environment that involves patients’ amplified role in shaping their treatment it is objected to not only mitigate the presenting symptoms but also enhance the overall well-being of the patients. Furthermore, the significance of effective BPSD management extends beyond the patient alone. The implications of efficient BPSD treatment ripple outward, ultimately alleviating the considerable burden placed on caregivers who provide unwavering support to individuals with BPSD. Takahashi et al. (2020) found that improving BPSD patients’ care translates into a marked reduction in the caregiving load, thus enhancing the quality of life for patients and their caregivers.

Study strengths and limitations

This study only includes RCTs; quantitative analysis was used to examine the statistical significance. In addition, publication analysis with funnel plots was also carried out. Variations in the intervention administration, stadium of dementia, ingredients contained in the essential oil intervention, and weeks of follow-up periods in this study suggest broad generalizability. However, it also may hinder claiming specific effects due to its variations, which are solved with a part of the biomolecular mechanism discussion.

Based on the systematic search that has been carried out, this study is the first to explain how EO affects indicators of agitated behavior in dementia patients—those indicators, namely survival risk, CMAI, and NPI. Previous studies only reviewed the overall potential effect of EO as a behavior-based therapy for dementia patients coupled with its neuropharmacology mechanism without addressing its particular mechanism to the occurrence of psychiatric symptoms. There have not been any systematic reviews using specific parameters regarding the agitated behavior of dementia quantitatively.

There are some limitations of the study. Firstly, we are unable to examine the impact of the patient's history due to the lack of reporting. Secondly, there were several variances, as mentioned, which led to the heterogeneity of the study. Thirdly, as essential oil’s mechanism is molecular-based, a comprehensive molecular analysis of its ligand bond must be done to broaden the discussion.