Passiflora Incarnata L. Herba in the Treatment of Anxiety Symptoms and Insomnia in Children and Adolescents with Feeding and Eating Disorders

Abstract

Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy.

1. Introduction

Feeding and Eating Disorders (FEDs) are significant mental health conditions that frequently manifest during childhood or adolescence, with their prevalence steadily increasing [1]. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), categorizes FEDs into well-known diagnostic categories such as anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Additionally, the DSM-5 includes avoidant/restrictive food intake disorder (ARFID), pica, rumination disorder and Other Specified Feeding and Eating Disorder (OSFED) and Unspecified Feeding or Eating Disorder (UFED) [2]. While all FEDs can present across the age spectrum, AN and ARFID are more commonly diagnosed in childhood and adolescence, whereas BN and BED are rare in pediatric populations [3].

FEDs often co-occur with several medical conditions, including diabetes, cardiac problems, and gastrointestinal disorders, as well as psychiatric conditions such as anxiety, depression, and substance use disorders [4]. Notably, individuals with FEDs have an increased risk of experiencing sleep disturbances, with those suffering from AN exhibiting more pronounced sleep issues compared to individuals with depressive disorders [5].

The Canadian Practice Guidelines for the treatment of children and adolescents with eating disorders (2020) strongly recommend Family-Based Treatment (FBT) and provide weaker recommendations for Multi-Family Therapy (MFT), cognitive–behavioral therapy (CBT), and Adolescent-Focused Psychotherapy (AFP) [6]. Although medications are not typically the primary mode of treatment for FEDs, they are frequently prescribed as adjuncts to other therapeutic interventions [7]. Short-term efficacy of medications, especially selective serotonin reuptake inhibitors (SSRIs), has been observed in reducing binge eating behaviors in BN and BED and in managing comorbidities such as anxiety and depression [7,8]. Additionally, second-generation antipsychotic medications, combined with behavioral interventions, may be considered to address the rigidly held cognitions and intense anxiety characteristic of FEDs, especially AN [7].

Phytotherapy has emerged as a potential option for managing anxiety symptoms and insomnia during the developmental stages [9]. Among herbal medicines, Passiflora incarnata (passionflower) stands out due to its well-documented therapeutic properties. The aerial parts of the plant, including flowers and fruits, are utilized for medicinal purposes [10]. Particularly, delving deeper into its pharmacological mechanisms, Passiflora incarnata is known for its high content of flavonoids, such as chrysin, apigenin, and luteolin, compounds that are believed to modulate the neurotransmitter system. The mechanism of action is believed to involve the modulation of the γ-aminobutyric acid (GABA) system, as Passiflora flavonoids act as partial agonists of GABA A receptors and inhibit the uptake of [3H]-GABA into rat cortical synaptosomes [11]. Furthermore, a role should also be played in the modulation of the serotonin and adrenergic system, both critically involved in regulating anxiety, mood and stress responses [12].

While benzodiazepines (BZDs) are a common class of drugs used to treat anxiety disorders, they present several drawbacks, including non-responsiveness in a significant percentage of patients (approximately 25%), the development of tolerance and potential dependence, and side effects such as sedation and cognitive impairment. Consequently, there is a demand for safer alternative treatments [13]. Passiflora incarnata has not been associated with adverse effects such as memory loss or cognitive function impairment. Its anxiolytic effects are described as comparable to those of medications like oxazepam or midazolam, making it an effective and safe option for reducing stress reactivity, insomnia, anxiety, and depression-like behaviors [10]. In the recent literature, numerous clinical studies have reported its potential application in pediatric clinical practice [12,14].

Reflecting on potential interactions with other medications, some studies have reported that Passiflora incarnata L. Herba may interact with central nervous system (CNS) depressants—such as benzodiazepines, sedatives, and alcohol—potentially enhancing sedative effects and increasing the risk of drowsiness and somnolence [12].

The present study is the first one to specifically describe its use in children and adolescents with FEDs co-occurring with anxiety and insomnia. The aim of this study is to explore the use of Passiflora incarnata L. Herba, administered as tablets (each containing 200 mg of dry extract, an equivalent dose of 700–1000 mg of Passionflower extract obtained using ethanol 60% v/v as the extraction solvent), in conjunction with traditional psychopharmacological therapies, in this patient population.

2. Materials and Methods

This is an observational retrospective study. This study was conducted in the context of observational research investigating the use of psychopharmacological treatments in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents and was approved by the local ethical committee (code NPI-DAPSIFA2020). This study was conducted in July 2024 by retrospectively considering patients assessed at the study Center between 1 January 2020 and 31 December 2023, and with at least one outpatient visit or hospitalization for FEDs at the same center. A high volume of pediatric and adolescent FED case reaches the center, ensuring a sufficient and diverse clinical population for observational research. Additionally, it serves as a regional hub for the diagnosis and treatment of complex FEDs, covering a broad geographical area and receiving referrals from multiple local health units.

The inclusion criteria were (a) a diagnosis of FED according to the DSM-5 criteria and (b) a received treatment with Passiflora incarnata L. Herba (tablets containing 200 mg of dry extract) lasting at least one month. The exclusion criteria were insufficient clinical documentation.

All the patients received an assessment for FEDs upon admission to our center. Besides pharmacological interventions, the considered variables included demographics (gender, age), and clinical variables (FED subtype, comorbidities). During follow-up, the effects of Passiflora incarnata L. Herba on the debilitating comorbidities of FEDs were observed and the concomitant effect of administrating drug therapy was monitored. To evaluate the clinical benefit for patients, the Clinical Global Impressions (CGI-I) scale was employed. This well-established research rating tool assesses the clinician’s perspective on the patient’s overall functioning before and after starting a study medication. The CGI is rated on a 7-point scale, with the severity-of-illness scale using a range of responses from 1 (very much improved) through to 7 (very much worse). The rating is based on observed and reported symptoms, behavior and function in the past seven days [15]. For a comparative analysis of the effects of Passiflora incarnata L. Herba across the sample, the patients were grouped based on the following factors: target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used.

Descriptive analyses were provided for the entire sample. The significance level was set at 0.05. All statistical analyses were performed using JASP.

3. Results

3.1. Demographic and Clinical Profile of the Sample

The sample includes 94 patients (88.3% female, 11.7% male). The average age is 15.0 years (SD 1.78, min. 8.6, max. 17.9). The most prevalent FED diagnoses are anorexia nervosa (71.3%) and atypical anorexia nervosa (10.6%). Other diagnoses include ARFID 3.2%, BED 6.4%, BN 3.2%, atypical BN 2.1%, and OSFED 3.2%.

Passiflora incarnata L. Herba was used at a dose of 200 mg of dry extract (equivalent to 700 mg–1000 mg). The dose varied from 1 to 2 tablets per day (n = 41, 43.6% took 1 tablet per day; n = 53, 56.4% took 2 tablets per day).

Regarding the duration of treatment, 22 patients (23.4%) took Passiflora incarnata L. Herba for less than 3 months; 27 patients (28.7%) for more than 3 months; in 35 patients (37.2%), treatment with Passiflora incarnata L. Herba was still ongoing. Finally, in 10 patients (10.6%), the relevant data could not be retrieved.

There were 53 (56.4%) patients receiving concomitant treatment with antidepressants, 26 (27.7%) with atypical antipsychotics, and 7 (7.4%) with benzodiazepines (in three cases as needed).

Regarding comorbidities identified in our sample, the most frequent were anxious-depressive traits (seven patients, 7.4%); four patients (4.3%) had a diagnosis of Specific Learning Disorders; two patients (2.2%) had a diagnosis of epilepsy. Less frequently diagnosed were Type 1 Diabetes (n = 1); ADHD (n = 1), dilated cardiomyopathy (n = 1), and headache (n = 1).

3.2. Clinical Outcomes and Subjective Benefits

As regards the effect, 64 patients (68.0%) had retrospective data on treatment outcomes. The benefit of Passiflora incarnata L. Herba was assessed using the CGI-I based on the clinician’s evaluation. The assessment was informed by the clinical interview and the mental state examination conducted during follow-up appointments. Specifically, 34 patients (53.1% of the sample with data on treatment outcomes) reported benefit from the intake, obtaining a score of 2 (n = 23, 35.9%) or 3 (n = 11, 17.2%); 30 patients (46.8%) reported no benefit, obtaining a score of 4. No clinical worsening or side effects were recorded.

To better characterize the population reporting a benefit, the sample was divided into two groups based on target symptoms. The first group included 45/64 patients (70.3%) who used Passiflora incarnata L.Herba for anxiety symptoms, while the second group comprised 22/64 patients (34.3%) who used Passiflora incarnata L. Herba for insomnia (four patients used Passiflora incarnata L. Herba to target both anxiety and insomnia symptoms). In the first group, 24/45 patients (53.3%) reported an improvement in symptoms, obtaining a CGI-I score of 2 or 3, while 21/45 patients (46.7%) reported no benefit (CGI-I: 4). No significant difference was found from this analysis (X2 = 3.219, p = 0.200). In the second group, 10/22 patients (45.4%) reported an improvement in symptoms, obtaining a score of 2 on CGI-I, while 12/22 patients (54.5%) reported no benefit (CGI-I: 4). This difference was statistically significant (X2 = 7.028, p = 0.030).

Additionally, subjective benefit was compared between patients on polytherapy and those on Passiflora incarnata L.Herba alone. No statistically significant difference emerged from this analysis. Regarding the 41/64 patients on SSRI therapy, 24 patients reported a benefit following the intake of Passiflora incarnata L. Herba, obtaining a score of 2 or 3, while 17 patients scored 4, reporting no benefit (X2 = 1.374; p = 0.503) Among the 17/64 patients on polytherapy with atypical antipsychotics, 10 patients obtained a score of 2 or 3, and 7 patients scored 4, reporting no benefit (X2 = 0.340, p = 0.844). Fourteen patients (14/64) were on polytherapy with SSRI and atypical antipsychotic, and of these, nine patients obtained a score of 2 or 3, while five patients scored 4 (X2 = 0.902, p = 0.729). Twenty-one (21/64) were treated solely with Passiflora incarnata L. Herba. Of these, 10 obtained a score of 2 or 3, while 11 patients scored 4 (X2 = 0.414, p = 0.813).

Finally, the subjective benefit reported was compared based on the diagnosis of FED. No statistically significant difference emerged from this analysis (X2 = 9.61, p = 0.644). Specifically, among the 49/64 patients (76.5%) diagnosed with AN, 27 patients reported a benefit following Passiflora incarnata L. Herba intake, obtaining a score of 2 or 3, while 22 patients reported no benefit. Of the 4/64 patients (6.2%) diagnosed with atypical AN, only two patients reported subjective benefit (CGI-I 2 and 3), and two patients reported no benefit. Within the sample, only 1/64 patients (1.6%) were diagnosed with ARFID, and no subjective benefit were reported following the intake of Passiflora incarnata L. Herba. Among the 5/64 (7.8%) patients diagnosed with BED, two patients reported subjective benefit (CGI-I 2 and 3), and three patients reported no benefit. Finally, among 2/64 patients diagnosed with BN (4.1%), two reported benefit (CGI-I of 2), and of the 1/64 patients diagnosed with atypical BN (1.6%), one obtained a score of 2 on CGI-I.

4. Discussion

This is the first paper to specifically describe the use of Passiflora incarnata L. Herba in children and adolescents with FEDs co-occurring with anxiety and insomnia. Anxiety symptoms and insomnia are highly prevalent and often clinically significant in the context of FEDs, contributing to both symptom severity and treatment resistance. The management of anxiety and sleep disturbances in youth with FEDs is complex due to their increased vulnerability to adverse pharmacological effects and frequent polypharmacy. For this reason, there is a growing clinical interest in identifying safe, well-tolerated, and evidence-based alternative interventions.

Our study found that 53.3% of patients who used Passiflora incarnata L. Herba for anxiety symptoms reported a significant improvement, which aligns with the literature documenting its anxiolytic effects [10]. This finding supports the potential role of Passiflora incarnata L. Herba as a complementary treatment for anxiety in FEDs. Our results are in line with previous studies that reported an improvement of up to 50% in anxiety symptoms with traditional anxiolytics [13]. This result could be also attributed to the complexity and the underlying subtypes of anxiety in FEDs. In fact, comorbid anxiety symptoms in this population may have varying impacts on the pathophysiology of FEDs. In some cases, higher levels of anxiety may lead to the adoption of dysfunctional emotion regulation strategies, such as disordered eating behaviors (e.g., binge eating). In other situations, anxiety may be more closely related to social issues. For instance, low self-esteem, combined with a negative self-perception and body dissatisfaction, may represent risk factors for the development of a FED or for aggravating the clinical picture. This observation suggests that clinicians might reflect on the potential benefits of using adjusted doses, or consider combining Passiflora incarnata L. Herba with other interventions to enhance its clinical efficacy [16].

Regarding insomnia, our results showed a statistically significant improvement in 45.4% of patients, which is notable given the challenging nature of treating sleep disturbances in FEDs. This finding is promising and suggests that Passiflora incarnata L. Herba might be a valuable addition to treatment regimens. Prior studies have highlighted the efficacy of Passiflora incarnata L. Herba in improving sleep quality without the adverse effects associated with benzodiazepines [9]. The lower improvement rate in our study, compared to some research reporting an improvement of up to 60% [11], might be due to the wide variety of symptoms that could compromise sleep quality in FED patients. Longer sleep onset latency, insufficient sleep and sleep fragmentation have been reported in the recent literature. In our study, sleep disorders were treated as a single category without further subdivisions. More detailed research should explore optimal dosing and combination therapies to maximize benefits for sleep disturbances in this population.

Our study also found no significant difference in the efficacy of Passiflora incarnata L. Herba between patients receiving monotherapy and those on polytherapy. This suggests that Passiflora incarnata L. Herba can be effectively integrated into existing treatment plans without diminishing its efficacy. These findings are consistent with the literature indicating the versatility of Passiflora incarnata L. Herba in various therapeutic contexts [10]. The lack of significant difference might also highlight the non-specific effects of herbal treatments across different comorbid conditions. Clinicians should consider Passiflora incarnata L. Herba as a viable option for enhancing treatment in complex FED cases, regardless of current pharmacotherapy.

Lastly, we observed varying responses to Passiflora incarnata L. Herba based on FED diagnosis, with patients with AN reporting the most benefit. This aligns with the existing literature suggesting that AN patients may have a higher propensity for anxiety and related disorders [3]. However, the lower efficacy in other FEDs, such as BED and ARFID, might indicate distinct underlying mechanisms of anxiety and insomnia in these disorders. Although recent research is scarce, certain behaviors in these populations could compromise treatment outcomes. For instance, individuals with BED may experience binge eating episodes in the evening, potentially disrupting their circadian rhythm [17]. Delving deeper into anxiety symptoms, the ARFID population may have a less effective response due to the etiology of this disorder. Indeed, individuals with ARFID experience high levels of eating-related anxiety when they are confronted with certain foods or exposed to particular smells and textures. This means that, as with other anxiety disorders, eating-related anxiety in ARFID could have a better improvement with a combined cognitive–behavioral therapy [18].

In conclusion, the variability in response to Passiflora incarnata L. Herba observed across different FED diagnoses may be influenced by several clinical factors. First, symptom severity—particularly the intensity and chronicity of anxiety or insomnia—may play a key role in determining the efficacy of the intervention. Patients with more severe or persistent symptoms may require longer treatment periods or higher doses to achieve significant improvements.

Second, the presence of psychiatric comorbidities could interfere with treatment outcomes by introducing additional layers of clinical complexity.

Finally, treatment duration and adherence may also influence the degree of improvement observed. Since herbal remedies often have a more gradual onset of action compared to conventional medications, longer treatment courses might be necessary to observe their full therapeutic potential.

These differences could inform tailored therapeutic approaches, suggesting that while Passiflora incarnata L. Herba is beneficial for AN, alternative or additional treatments might be necessary for other FEDs. Further research is needed to understand these diagnostic-specific responses better and to develop targeted interventions.

A major strength of our study is its pioneering nature in examining the use of Passiflora incarnata in a pediatric FED population, providing valuable preliminary data. The inclusion of a diverse range of FED diagnoses and the assessment of both anxiety and insomnia adds to the robustness of our findings. However, there are several limitations. The size of the group with data in terms of effectiveness is relatively small (n = 64), and this study lacks a control group, which limits the generalizability and causal inferences of our results. The retrospective nature of data collection also introduces potential biases, and as previously mentioned, the variability in treatment duration and dosages among patients complicates the analysis. Future studies should aim for larger, controlled trials with standardized treatment protocols to validate and expand upon our findings; it will be important to also include multicenter or multinational samples. Comparative analyses with other herbal compounds could further substantiate the role of phytotherapy as an adjunctive intervention in this field. This would allow for a more comprehensive evaluation of both efficacy and safety profiles across diverse clinical contexts.

5. Conclusions

In conclusion, our study is the first to explore the use of Passiflora incarnata L. Herba in children and adolescents with Feeding and Eating Disorders co-occurring with anxiety and insomnia. Our findings suggest that Passiflora incarnata L. Herba may offer a beneficial adjunctive treatment for anxiety and sleep disturbances in patients with FEDs. This phytotherapeutic option demonstrated excellent tolerability, with no reported adverse effects or drug interactions. Therefore, it may represent a valuable choice for clinicians in cases where symptoms are mildly expressed or when caregivers are hesitant about conventional pharmacological treatments.

Notably, Passiflora incarnata L. Herba intake at a dosage of 200–400 mg per day was associated with symptom improvement in an average of 53% of patients. Furthermore, 53.3% patients using Passiflora incarnata L. Herba for anxiety and 45.4% for insomnia, reported meaningful symptomatic relief. These findings underscore the potential utility of this plant-based treatment in addressing common comorbidities in FED populations.

Moreover, its favorable safety profile and the encouraging preliminary results observed in this study should encourage further controlled trials exploring phytotherapy-based strategies, especially in vulnerable populations such as children and adolescents with FEDs. However, the variability in treatment response across different FED subtypes highlights the need for additional research to optimize therapeutic approaches. Future studies should focus on larger, well-designed clinical trials to confirm these findings and to refine dosing protocols and potential combination strategies aimed at maximizing clinical benefit.

Future research may explore several promising directions. One potential avenue involves examining the synergistic effects of Passiflora incarnata when combined with other herbal treatments in the management of anxiety, sleep disturbances, and mood disorders. Another important direction could be the investigation of the potential benefits of integrating Passiflora incarnata with FBT, CBT or other psychological interventions to enhance therapeutic outcomes in anxiety and stress-related conditions. Finally, comparative studies assessing the clinical effectiveness of Passiflora incarnata versus established anxiolytics, such as benzodiazepines or selective serotonin reuptake inhibitors (SSRIs), could provide another valuable insight into its role as a complementary or alternative treatment option for anxiety and depression.

The use of herbal medicines to prevent, treat, mitigate, diagnose, or cure different pathological conditions has not been consistently addressed at a global level. The major limitation is the lack of randomized controlled trials in large populations with homogeneous characteristics. However, the reporting in the literature of experiences such as the one we have reported may represent an added value to knowledge that surely requires confirmation. Future studies should aim for larger, controlled trials with standardized treatment protocols to validate and expand upon our findings; it will be important to also include multicenter or multinational samples. Comparative analyses with other herbal compounds could further substantiate the role of phytotherapy as an adjunctive intervention in this field. This would allow for a more comprehensive evaluation of both efficacy and safety profiles across diverse clinical contexts. Equally, it would be relevant that such preparations are used in all future pharmacological and clinical studies.