Effect of Citrus aurantium capsules on peripartum anxiety and postpartum blues: a randomized triple -blind clinical trial

Abstract

Background and aim

Maternal anxiety and blue during pregnancy and postpartum can have significant negative effects on mother, child and family. In recent years, the people of Iran, like other countries in the world have paid special attention to the use of medicinal plants due to the side effects of chemical drugs, one of the medicinal plants with sedative and anti-anxiety effects is Citrus aurantium. The aim of this study was to investigate the effect of Citrus aurantium capsules on peripartum anxiety and postpartum blues.

Methods

In the present clinical trial, 100 pregnant women with anxiety diagnosis were included in the study and randomly divided into control and case groups. The intervention group received 500 mg of Citrus aurantium capsule twice daily and the control group received placebo for 6 weeks (two weeks after delivery). Beck Anxiety Questionnaire was completed before the intervention, immediately after delivery and 2 weeks after delivery, and the postpartum blues checklist was completed immediately after delivery and 2 weeks after delivery. Data were analyzed by SPSS software.

Results

The mean anxiety score of the control group at two weeks postpartum was significantly lower than before the intervention (P < 0.05) but at the time of delivery was not significantly different from before the intervention. The mean score of anxiety in the intervention group during delivery and two weeks after delivery was significantly lower than before the intervention (P < 0.05). The mean score of anxiety in the intervention group during the study period was significantly lower than the control group (P < 0.05). The frequency of labor grief during labor in the control and intervention groups did not show a significant difference (P > 0.05), but two weeks after delivery the frequency of labor grief in the intervention group with 28% was significantly lower than the control group with It was 54% (P < 0.05).

Conclusion

Citrus aurantium capsule reduces anxiety during and after childbirth and is recommended for use in anxious patients.

Trial number

IRCT20210926052594N1 Registration date: 2021-10-09.

Introduction

Mental disorders are among the leading causes of disability worldwide and rank as the third major contributor to the global burden of disease [1]. According to the World Health Organization (WHO), anxiety disorders are the most common mental health disorders, followed by depression [2]. Although anxiety is a natural response to threatening situations, it becomes a psychological disorder when it occurs in the absence of real danger or persists excessively after the threat has passed [3]. In Iran, the prevalence of anxiety disorders is estimated at 31%, with women being two – three times more likely than men to experience such conditions [4, 5].

Pregnancy, due to its associated physical, emotional, and social changes, is a vulnerable period for women and often leads to increased levels of anxiety, particularly during the first and third trimesters [6]. Fear of childbirth affects approximately 30% of pregnant women, with 10–11% experiencing severe fear, which is linked to obstetric complications, negative birth experiences, and increased rates of emergency cesarean Sects [7, 8]. Severe anxiety during pregnancy can also increase the risk of postpartum depression and anxiety [9].

In the postpartum period, psychological conditions such as anxiety and postpartum blues are also common. Approximately one in ten women suffers from elevated levels of anxiety and/or depression after childbirth, with some studies reporting a prevalence as high as 25% [10]. Postpartum blues typically begin within a few days of delivery and may last up to two weeks, manifesting with symptoms such as tearfulness, mild depression, anxiety, and mood fluctuations. Reported prevalence rates of postpartum blues range from 4% to 80% depending on the study [11]. In more severe cases, further psychiatric evaluation is necessary to rule out postpartum depression or anxiety [11].

While pharmacological treatments may alleviate anxiety and mood disturbances during and after pregnancy, their potential side effects on the newborn have raised concerns. Consequently, researchers have increasingly explored alternative, safer interventions, including complementary and herbal therapies [6]. Among these, herbal medicines such as valerian, chamomile, lavender, borage, and Citrus aurantium have demonstrated anxiolytic effects in various clinical studies [12].

Citrus aurantium, traditionally used in Iranian medicine for treating nervous conditions such as hysteria and nervous weakness, are known for their calming, sleep-inducing, appetite-stimulating, and heart rate-regulating effects [13]. These effects are attributed to compounds like flavonoids, which act as benzodiazepine receptor agonists and reduce anxiety through similar mechanisms [14]. Citrus aurantium is recognized by the U.S. Food and Drug Administration (FDA) and classified as a Category I herb by the American Herbal Products Association (AHPA), indicating safety for use during pregnancy [15].

Evidence from preclinical research supports the biological plausibility of these effects. Animal studies have demonstrated that Citrus aurantium extracts and essential oils exert significant anxiolytic-like activity in standard behavioral models, such as the elevated plus maze and open-field test, potentially mediated by modulation of the GABAergic system and benzodiazepine receptor activity [14, 16]. Saketi et al. (2014) also reported that Citrus aurantium essential oil significantly reduced anxiety-related behaviors in male mice and showed interaction effects with fluoxetine, further supporting its anxiolytic potential [16]. In vitro investigations indicate that flavonoids, including hesperidin and naringin, present in Citrus aurantium flowers, possess antioxidant and anti-inflammatory properties, and may modulate serotonergic and GABAergic neurotransmission, thereby contributing to mood regulation and anxiolytic effects [14]. These mechanistic findings provide a scientific rationale for evaluating its potential in anxiety-related conditions.

Several studies have supported the efficacy of Citrus aurantium in reducing anxiety. Shabanian et al. (2009) found it to be an effective preoperative anxiolytic comparable to diazepam [17]. Namazi et al. (2014) reported its benefits in reducing anxiety and pain during labor through aromatherapy [12, 18]. In a study by Zare et al. (2018), combining powdered Citrus aurantium capsules with fluoxetine was more effective than fluoxetine alone in treating mild to moderate postpartum depression [19]. Additionally, a systematic review by Mannucci et al. (2018) concluded that Citrus aurantium significantly reduces anxiety levels [20]. More recently, a systematic review by Yilmaz (2026) reported that Citrus aurantium is an effective non-pharmacological intervention with significant therapeutic effects on various aspects of women’s health across different life stages [21].

Given the high prevalence of anxiety and postpartum mood disturbances, their adverse effects on maternal and neonatal health, and the limitations of conventional pharmacological treatments, there is a growing need to explore safe and effective complementary approaches. This study aims to evaluate the effect of Citrus aurantium capsules on peripartum anxiety and postpartum blues.

Materials and methods

Study design and sampling

This randomized triple-blind clinical trial was conducted on 100 pregnant women at 36 weeks of gestation who visited Hajar Hospital in Shahrekord and were clinically diagnosed with mild to moderate anxiety. According to previous studies and the sample size calculation formula presented below, 100 participants were selected using convenience sampling (by SS).

d=

Z₁-α/2 = 1.96.

Z₁-β = 0.84.

d = 0.28.

n = 100.

Inclusion and exclusion criteria

Inclusion criteria were: informed consent, age between 18 and 35 years, literacy (able to read and write), at least 36 weeks of pregnancy, confirmed mild to moderate anxiety through clinical interview, no history of allergy to herbal medicines, low-risk pregnancy, no chronic diseases and no addiction to narcotics and exclusion criteria included: unwillingness to continue participation, occurrence of drug side effects or hypersensitivity and failure to take the capsules for three consecutive days.

Data collection tools

Data collection instruments included an interview form (covering demographic information, fertility history, and marital life), the Beck Anxiety Inventory (BAI), the Postpartum Blues Checklist, and a Drug Side Effects Questionnaire. The BAI consists of 21 items scored on a 0–3 scale, with total scores ranging from 0 to 63, categorized into four anxiety levels. The Postpartum Blues Checklist includes six symptoms, with the presence of at least three indicating postpartum blues. The Drug Side Effects Questionnaire was specifically designed to record any harm, adverse effects, or discomfort experienced by participants during the study period. This questionnaire included both closed-ended questions, allowing participants to indicate the presence or absence of predefined side effects, and open-ended questions for reporting any additional experiences not listed.

Study procedure

After obtaining approval from the institutional ethics committee and registering the trial in the relevant clinical trial registry, eligible participants were provided with detailed information about the study objectives, procedures, potential benefits, and risks. Written informed consent was then obtained from all participants. Using a simple randomization method via the website randomizer.org, participants were randomly assigned to either the intervention or control group.

Participants in the intervention group received 500 mg capsules containing dried Citrus aurantium (Bitter Orange flower) powder, supplied as a ready-to-use herbal product by Barij Essence Pharmaceutical Co. (Kashan, Iran). The capsules were used as provided by the manufacturer, without any additional processing by the research team. The control group received placebo capsules containing starch, administered in the same manner. To ensure allocation concealment and minimize bias, delivery of the capsules and instructions for their use were carried out by an individual independent of the research team and unaware of the group allocations. Moreover, data analysis was performed by a blinded statistician who was not informed of group assignments.

The anxiety questionnaire was completed by participants at three time points: before the intervention, immediately after childbirth, and two weeks postpartum. The postpartum grief checklist was also collected at two time points: immediately after delivery and again two weeks later.

Data analysis

Data were entered into SPSS version 18 and analyzed using descriptive statistics (frequency, percentage, mean, standard deviation) and inferential tests including independent t-test, Chi-square test, Fisher’s exact test, and repeated measures analysis with post-hoc Tukey test. The significance level was set at p < 0.05. Results are reported as mean ± standard error of the mean (SEM).

Results

In this study, 100 pregnant women were randomly assigned to intervention and control groups (Fig. 1).

Fig. 1.

Participant flow diagram

There were no significant differences between the two groups in terms of maternal age, husband’s age, marriage duration, number of previous children, type of delivery, pregnancy complications, FHR before delivery, gestational age, type of pregnancy, history of miscarriage, prenatal care, and infant feeding (P > 0.05). However, there was a statistically significant difference in intrapartum FHR status: 24% in the control group and 6% in the intervention group had non-reactive FHR (P = 0.012*) (Table 1).

Table 1.

Comparison of demographic and clinical characteristics

Variable		Control Group	Intervention Group	P-Value
Maternal Age (mean ± SD)		25.96 ± 4.74	26.00 ± 4.81	0.957
Husband’s Age (mean ± SD)		30.12 ± 4.83	30.40 ± 4.84	0.773
Duration of Marriage (years)		3.40 ± 2.30	3.48 ± 2.36	0.864
Number of Previous Children		1.70 ± 0.84	1.62 ± 0.78	0.622
Type of Delivery (n (%))	Vaginal	32 (64%)	32 (64%) Vaginal /	1.000
	Cesarean	18 (36%)	18 (36%) Cesarean
Pregnancy Complications (n (%))	Yes	8 (16%)	10 (20%) Yes / 40	0.603
	No	42 (84%)	(80%) No
FHR Before Delivery (n (%))	Reactive	46 (92%)	45 (90%)	1.000
	Non-reactive	4 (8%)	5 (10%)
Gestational Age (n (%))	Preterm	7 (14%)	5 (10%)	0.625
	Term	37(74%)	41(82%)
	Post-term	6 (12%)	4 (8%)
Type of Pregnancy (n (%))	Wanted	24 (48%)	23 (46%)	0.841
	Unwanted	26 (52%)	27 (54%)
History of Abortion (n (%))	Yes	10 (20%)	10 (20%)	1.000
	No	40 (80%)	40 (80%)
Regular Prenatal/Postnatal Care (n (%))	Yes	41 (82%)	40 (80%)	0.799
	No	9 (18%)	10 (20%)
Infant Feeding Type (n (%))	Breastfeeding	41 (82%)	40 (80%)	0.799
	Formula	9 (18%)	10 (20%)
FHR During Labor (n (%))	Reactive	38 (76%)	47 (94%)	0.012*
	Non-reactive	12 (24%)	3 (6%)

*p < 0.05; significance

Comparison of anxiety scores

Repeated measures ANOVA showed that:

• In the intervention group, mean anxiety scores significantly decreased across the three time points (before intervention, during labor, and two weeks postpartum) (P<0.001).

• In the control group, only the score two weeks postpartum showed a significant reduction compared to pre-intervention (P=0.002), while the score during labor was not significantly different (p ≥ 0.05).

At all-time points, anxiety scores were significantly lower in the intervention group compared to the control group (P < 0.001) (Table 2).

Table 2.

Comparison of anxiety scores before intervention, during labor and two weeks postpartum

Time Point	Control Group (Mean ± SD)	Intervention Group (Mean ± SD)
Before Intervention	11.38 ± 2.18	11.76 ± 2.27
During Labor	10.50 ± 2.61	5.90 ± 3.58
Two Weeks Postpartum	9.56 ± 3.06	3.48 ± 2.74

Comparison of postpartum blues

Regarding postpartum blues:

• During labor: No significant difference was observed between the two groups (P = 0.826).

• Two weeks postpartum: 54% in the control group and 28% in the intervention group experienced blues, indicating a significant difference (P = 0.008*) (Table 3).

Table 3.

Comparison of postpartum blues during labor and two weeks postpartum

Time	Control Group	Intervention Group	P-Value
During Labor	14 (28%)	15 (30%)	0.826
Two Weeks Postpartum	27 (54%)	14 (28%)	0.008*

*p < 0.05; significance

Finally, it should be noted that neither group reported experiencing any harm or adverse effects.

Discussion

Anxiety is a widespread, unpleasant, and vague emotional state of uneasiness, often with an unknown origin. It includes symptoms such as uncertainty, helplessness, and physiological arousal [22]. The postpartum period is a transitional phase into motherhood that involves new responsibilities and adaptations, even for multiparous women [23]. Today, complementary medicine has gained a prominent role as a modern method in the care of women during pregnancy, labor, and postpartum [12].

Citrus aurantium (Bitter Orange) has long been used in traditional Iranian medicine for its sedative, hypnotic, and anxiolytic properties [24]. Its anxiolytic effects have been validated in both animal models [25] and clinical trials [12, 26]. However, human studies on its effect—particularly in the postpartum period—remain limited. Most existing research has focused on its impact via aromatherapy or in experimental settings. To date, no prior study has examined its impact on postpartum blues. Therefore, the present study aimed to evaluate the effect of Citrus aurantium powder capsules on anxiety during labor and postpartum, as well as its potential to reduce postpartum blues.

This randomized clinical trial included 100 pregnant women with mild to moderate anxiety who were assigned to intervention and control groups. The groups were matched in terms of demographic and obstetric characteristics. The intervention group received 500 mg Citrus aurantium capsules twice daily for six weeks (until two weeks postpartum), while the control group received a placebo. Beck Anxiety Inventory was administered at three time points: pre-intervention, during labor, and two weeks postpartum. Additionally, postpartum blues checklists were completed immediately after delivery and at the two-week follow-up.

Findings showed a significant decrease in anxiety scores in the control group only at two weeks postpartum, likely due to the natural decline in anxiety after childbirth. However, in the intervention group, anxiety scores significantly decreased during labor and two weeks postpartum compared to baseline. Furthermore, comparison between groups revealed significantly lower anxiety in the intervention group at both labor and postpartum time points.

These results suggest that Citrus aurantium powder capsules may be an effective and safe treatment for reducing peripartum anxiety. These findings are consistent with previous studies. For instance, Shabanian et al. (2008) reported a significant reduction in preoperative anxiety with the oral intake of Citrus aurantium hydrosol [17]. Similarly, Akhlaghi et al. (2011) demonstrated that Citrus aurantium capsules reduced anxiety in patients undergoing minor lower limb surgery [27]. Namazi et al. (2014) observed a significant decrease in first-stage labor anxiety using Citrus aurantium aromatherapy [18]. Mohammad Aliha et al. (2016) also found a reduction in anxiety and improvement in vital signs among patients with acute coronary syndrome following Citrus aurantium aromatherapy [26]. Fernandes et al. (2016) confirmed its anxiolytic effect in patients with chronic myeloid leukemia [28], and other studies supported its efficacy in dental procedures and pregnancy-related anxiety [24, 29, 30].

While both groups showed no significant difference in postpartum blues immediately after birth, a significant reduction was observed in the intervention group at two weeks postpartum (28%) compared to the control group (54%). Similar findings were reported by Moradi et al. (2025), who demonstrated that aromatherapy with Citrus aurantium essential oil significantly reduced depression, stress, and anxiety levels in pregnant women compared with the control group [31].

A systematic review by Aboualsoltani et al. (2020) concluded that Citrus aurantium, particularly its flowers, exerts beneficial effects on psychological symptoms such as anxiety, depression, and insomnia, with aromatherapy being the most commonly used administration method [32]. In addition, a recent systematic review by Yilmaz (2026) highlighted the beneficial role of Citrus aurantium as a non-pharmacological approach for improving several aspects of women’s health throughout different stages of life [21].

The anxiolytic mechanism of Citrus aurantium appears to involve GABAergic pathways. Its essential oil has been shown to reduce anxiety-related behavior in male mice, potentially via the GABA system, as its effects are enhanced by GABA agonists [33]. Key components like linalool, linalyl acetate, limonene, coumarin, and flavonoids [34], are known to have sedative effects, with studies suggesting their capacity to activate the GABAergic system [35–37]. GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, reduces CNS excitability and contributes to calming effects. Limonene, in particular, binds to GABA < sub> A</sub> receptors and enhances GABA release, leading to anxiolysis [36]. Coumarin has also been shown to increase GABA release by interacting with GABA < sub> A</sub> receptors [37].

Conclusion

Citrus aurantium powder capsules demonstrated significant efficacy in reducing anxiety during labor and in the postpartum period, as well as in alleviating postpartum blues. These findings align with prior studies and suggest that Citrus aurantium, with its low-risk profile and natural origin, may be a valuable adjunctive treatment for managing psychological symptoms in the perinatal period. Further large-scale and long-term.

Strengths and limitations of the study

Importantly, the present study is among the first to show that Citrus aurantium can reduce postpartum blues, with a significant reduction observed two weeks after delivery. While previous studies have explored its effect on postpartum depression [19], this study extends its potential therapeutic benefits to postpartum blues as well.

Other strengths of this study were the careful design of the research process, the use of validated data collection tools, and the emphasis on ethical considerations and the protection of participants’ rights. Additionally, recruiting participants from both public healthcare centers and private clinics increased the diversity of the sample and enhanced the generalizability of the findings.

Nevertheless, the study faced certain challenges. One potential limitation was the reluctance of some individuals to participate or fully cooperate throughout the program. To address this issue, comprehensive and clear explanations were provided regarding the objectives, procedures, and ethical aspects of the study. Participants were also informed that their involvement was entirely voluntary and that they had the right to withdraw at any time without any negative consequences.

Furthermore, due to the COVID-19 pandemic, the number of pregnant women visiting the primary healthcare center had significantly decreased. To overcome this obstacle and ensure an adequate sample size, data collection was extended to include patients from private clinics and obstetrician offices.

Abbreviations

AHPA

American Herbal Products Association

BAI

Beck Anxiety Inventory

CNS

Central Nervous System

CONSORT

Consolidated Standards of Reporting Trials

COVID-19

Coronavirus Disease 2019

FDA

Food and Drug Administration

FHR

Fetal Heart Rate

GABA

Gamma-Aminobutyric Acid

IRCT

Iranian Registry of Clinical Trials

SEM

Standard Error of the Mean

SPSS

Statistical Package for the Social Sciences

WHO

World Health Organization

Authors’ contributions

“F.S. and S.S. wrote the main manuscript text and H.G., F.A., S.S., F.D. and F.S. prepared Tables. All authors reviewed the manuscript”.

Funding

The budget of this project was provided by Shahrekord University of Medical Sciences.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author (S.S.) on reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with ethical principles related to research involving human participants and after obtaining approval from the Ethics Committee of Shahrekord University of Medical Sciences (Code: IR.SKUMS.REC.1400.006). All participants provided written informed consent after being fully informed about the study's objectives, procedures, and potential risks. Confidentiality of information and participants' rights were fully protected. In case of any adverse events or discomfort, appropriate care was provided, and participants were free to withdraw from the study at any time. This clinical trial was registered in the Iranian Registry of Clinical Trials (IRCT) under the registration number IRCT20210926052594N1 (Registration date: 2021-10-09). All procedures performed in this study were conducted in accordance with the ethical standards of the institutional and national research ethics guidelines of Iran, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Ethical standards for publication were followed, including accurate translation and citation of all sources. Participants were acknowledged and thanked for their contribution.

Consent for publication

Consent for publication of anonymized data was also obtained. All stages of the study—including design, implementation, and reporting—were conducted in accordance with the CONSORT (Consolidated Standards of Reporting Trials) checklist to ensure methodological rigor and transparency in reporting.

Competing interests

The authors declare no competing interests.