Abstract
The current study aimed to evaluate the efficacy of jollab, a well-known beverage from traditional Persian medicine in the treatment of depression among patients suffering from functional dyspepsia. In a randomized, double-blind, placebo-controlled trial, a pair of 80 patients were enrolled in 2 parallel groups as Jollab and placebo. The Beck Depression Inventory–II questionnaire was used for the assessment. At all, 133 patients enrolling in the treatment and placebo groups ended the protocol. According to the outcomes, changes in scores between the 2 groups were statistically significant at the end of trial (P ≤ .001). Taken as a whole, treatment group was significantly more effective than the placebo. Focusing on nutritional and pharmaceutical properties, jollab may be introduced not only as a medication for depression and allied ailment but also a pleasant daily drink.
Introduction
Functional dyspepsia, one of the most common gastrointestinal disorders, is defined as the presence of abdominal pain or discomfort without any metabolic or organic disease clarifying the symptoms simply. 1 The prevalence of functional dyspepsia is estimated to range from 8% to 23% in Asia and is showing an increasing trend. 2,3 Epidemiological studies demonstrate similar findings in our country, Iran. 4,5 Numerous mechanisms have been introduced as the pathophysiology of this disorder, but it is considered as a heterogeneous condition. 6
Involvement of central nervous system is always a constant component in the list of suspicious mechanisms. 1 The higher frequency of psychiatric comorbidity among patients with functional dyspepsia is also an accepted fact. 7 One of the most investigated subjects in the aforementioned field is depression, which has been widely discussed. 8–10 On the other hand, depression is a prevalent disease worldwide and its prevalence was estimated at 4.1% in Iran. 11 Antidepressant drugs are a part of the treatment strategy of functional dyspepsia for a long time, although their adverse effects are a matter of interest. 7,12
Complementary and alternative medicine remedies are among suggested options for treatment of depression, claiming fewer side effects in comparison to contemporary medicine. 13 –15 Traditional Persian medicine scholars based on quadratic elements and resulting temperaments (mizadj), have also introduced many antidepressant medicines in their books. Jollab is a well-known beverage in traditional Persian medicine and has been recommended as an antidepressant agent repeatedly. 16 –18 Use of herbal medicines in treatment of depression is not a new issue but, well-designed randomized clinical trials in this filed are scanty. To our knowledge, there is no clinical trial evaluating the efficacy of jollab in depressed patients suffering from functional dyspepsia. The aim of this study was to evaluate the efficacy of jollab in the treatment of depression among patients suffering from functional dyspepsia.
Patients and Methods
Study Design
This was a randomized, double-blind, placebo-controlled, parallel-group, phase III clinical trial and conducted at Shahid Mottahari Clinic, affiliated to Shiraz University of Medical Sciences, Shiraz, Iran, from June 1 to November 30, 2013.
This study approved by the ethics committee of Shahid Beheshti Medical University, Tehran, Iran. Each patient signed a written informed consent and the trial was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613000584730).
Participants were individuals with age range of 18 to 65 years and diagnosis of functional dyspepsia according to the Rome III criteria. The diagnosis was confirmed through history taking, physical examination, and upper gastroendoscopy procedures.
The exclusion criteria were the following: progressive negative symptoms suggesting gastrointestinal malignancies and any form of diagnosed cancer, pulmonary, hepatic, endocrine, or immune system disease. Additionally, patients were excluded if they had established major psychiatric disorders like paranoid or major depressive disease; pregnancy or lactation; history of current drug abuse in the form of narcotics or alcohol dependency and consumption of antidepressant drugs during 6 weeks prior to enrolment.
Experimental Medication
As a popular beverage in traditional Persian medicine to cure depression, we used jollab in the current study. Jollab is a mixture of rose water, saffron, white rock candy, and water. All the ingredients were allowed and controlled by the Ministry of Health. Rose water is the byproduct of Damask rose petals (Rosa damascena Mill from the family Rosaceae) during the preparation of Rosa essential oil. 19 The saffron was drawn from the stigmas of Crocus sativus L (from the family Iridaceae) (Fayyazbahsh company, health certification code 36/1004). White rock candy was prepared from the Sepahan Company (health certification code 14-1002).
The preparation was made according to the instruction mentioned in the Canon of Medicine by Avicenna. Thus, rock candy was powdered, decocted, and dissolved in distilled water under mild fire. Uncrushed saffron was then suspended and macerated in to the mixture. 20 The daily dosage was 15 mL of prepared syrup, 3 times a day immediately after meals.
On the other hand, the placebo was designed with the same superficial properties using standard additives like edible dye. In the placebo beverage, rose water was diluted in water with the concentration of 1:10, with similar package and preservation and sterility tests of both beverages were performed prior to the trial.
Randomization
Randomization was done using a computer-generated program and a random code was assigned to every patient by an independent research coordinator. The treatment period was designed for 1-month duration. The randomization codes were tested at the end of the trial to assure that the blindness of the study was well kept.
Assessments
A well-recognized self-report tool for evaluation of depressive symptomatology in adult and adolescent groups is the Beck Depression Inventory–II. 21 This is a useful 21-part questionnaire, with an overall score ranging from 0 to 63 that has passed validation processes in earlier studies in Iranian population. 22,23 The patients stated their depressive symptoms, ranging from 0 (nothing) to 3 (severe), before and after the intervention through a valid questionnaire.
Outcome was defined as the improvement of depression in the form of reduction of total score based on the Beck Depression Inventory–II. Any side effects during the treatment period were recorded by patients. They also had the opportunity to call the first author so that they could report side effects in emergency situations.
Statistical Analysis
Based on our pilot study, we calculated the sample size as 78 patients in each group. Those who completed the trial were included in the analysis. Categorical variables were compared between the groups using chi-square test, and t tests were used to compare the continuous variables. Furthermore, all tests used SPSS (Version 18, Chicago, IL).
Results and Discussion
After screening, 18 patients did not meet the inclusion criteria, 32 persons met exclusion criteria and 3 participants refused to enroll the trial. Then, 160 patients divided in 2 groups as treatment and placebo groups. They received experimental medication (jollab) or placebo (15 mL 3 times after meal).
There was no difference in age (36.51 ± 11.71 vs 39.33 ± 11.56 years) between the treatment and placebo groups (P = .127), respectively as shown in Table 1. The body mass index showed no significant changes (24.0 ± 3.83 and 24.75 ± 4.65 kg/m2) between the 2 groups (P = .766), as well. Concerning the Beck Depression Inventory, both groups showed similar scores prior to the trial (P = .319). According to the outcomes, changes in scores between the 2 groups were statistically significant at the end of trial (P ≤ 0.001). Taken as a whole, the treatment group was significantly more effective than the placebo (Table 2).
Demographic Characteristics.
Data of Intervention Procedure.
Most of the participants successfully finished the trial (12 and 15 patients dropped out in jollab and placebo group, respectively). None of the patients reported any major or life threatening unwanted effects during the intervention.
Concerning the interest in use of the herbs and natural medicaments in the management of depression, there are some reports on the evaluation of these medicines. Herbal products alone or in adjutant therapy with conventional psychiatric medicaments have shown considerable effects in psychic disorders, either clinically or experimentally. 24 Melissa officinalis (lemon balm) ethanol extract was evaluated orally for 10 days in male and female Wistar rats for possible behavioral effects. 25 Lavandula angustifolia Mill tincture was assessed versus imipramine for the treatment of mild to moderate depression. In this 4-week double-blind, randomized trial, patients in 3 groups received the tincture (1:5 in 50% alcohol) 60 drops/day plus a placebo tablet, imipramine 100 mg/d plus placebo drop or imipramine 100 mg/d plus tincture 60 drops/d. Results showed that the combination of tincture and imipramine may serve better responses and benefits in the management of mild to moderate depression. 26 In another study, this medicinal plant showed a significant effect in treatment of major depressive disorder for 4 and 8 weeks of consumption in different dosage form. 27 In major depressive disprder, meta-analysis revealed that Hypericum perforatum (perforan) is as effective as conventional selective serotonin reuptake inhibitors or synthetic drugs with regard to the efficacy and adverse events. 28,29 In addition, a double-blind, randomized, placebo-controlled trial assessed the efficacy of this herb as an adjuvant with tricyclic antidepressants in major depressive disorder. Outcomes showed significant degree of recovery in perforan group as compared with the other group. 30
Other than these assessments, some researchers have studied the association of functional dyspepsia with depression and anxiety as well as possible effectiveness of current or natural medicines. 31 –33
Complementary and alternative medicine modalities, especially traditional Persian medicine, have introduced numerous food and herbal preparations for treatment of depression for a long time. 34,35 The current study was designed and performed to assess the effectiveness of a traditional preparation named jollab in the treatment of depression among patients suffering from functional dyspepsia. The preparation is well known by traditional Persian practitioners and has been administered for a variety of ailments since a long time. Concerning the chemical and nutritional compositions, the preparation contains Rosa aromatic water and saffron as well as rock candy and distilled water. Previous investigations have determined the major chemical constituents of the employed aromatic water. Results showed that phenethyl alcohol, geraniol, and β-citronellol were the main components. 19 Damask rose, as the origin of these constituents, has showed antidepressant activities in animal models. 36 A human study with rose oil showed that there was a significant improvement in aroma group as compared with placebo. 37 In an investigation, the respective effects were resulted from Damask rose aqueous extract, which definitely contains phenethyl alcohol. 38 This compound is found in fresh rose petals and may freely be extracted into the aqueous phase as rose water. In our study, jollab contained phenethyl alcohol as the main ingredient. 19 There are numerous pharmacological reports on the pure phenethyl alcohol but focused on the antimicrobial activities. However, further studies should be performed on this aromatic constituents, and its impact on depressive disorders needs further research.
The other medicinal herb in jollab preparation was saffron. Saffron with main constituents, crucin, picrocrocin (both as apocarotinoid glycosides), and safranal (breakdown products of the picrocrocin and as volatile constituent) 39 possesses many pharmacological properties. Properties related to depression and psychotic disorders have been proved in some investigations. Investigations have remarked that saffron can significantly reduce depression symptoms compared with placebo. Furthermore, in some studies saffron was found as effective as antidepressant medicaments. 40,43
Other than the proved antidepressant properties of jollab components (Rosa and saffron active ingredients) by prior related investigations, presence of the aroma constituents such as phenethyl alcohol, geraniol, and β-citronellol as main compositions of jollab might be the main reason for the improvement of dyspepsia. The aroma could also ameliorate the immune system resulting in better function of neurological system. 44 Since some relates mechanisms have been denoted for these aroma constituents, 45 jollab may be introduced as a safe and effective functional food for such ailment.
Limitations
Current work has evaluated the effectiveness of a medicinal beverage from traditional Persian medicine in the management of depression among patients suffering from dyspepsia. It is considerable to mention that we didn't aim to talk about the therapeutic effect of Jollab on functional dyspepsia as this was presented in another manuscript, ahead of print meanwhile. Although this performance may be of interest to the physicians, but the sample size should be increased to achieve comprehensive results. On the other side, it is worthy to evaluate the effectiveness of this drink in depressive patients, without considering other accompanied disorders. In this regard, results could be assessed more precisely.
Conclusion
Current study was performed to draw together the evidences on the efficacy and safety of a popular traditional beverage, jollab, used in traditional Persian medicine for psychiatric complications. Results revealed the effectiveness of this medicinal drink in comparison with placebo. Focusing on nutritional and pharmaceutical properties, jollab may be introduced not only as a medication for the studied ailment but also as a pleasant daily drink.
Footnotes
Acknowledgments
This work is a part of Mehdi Pasalar’s PhD dissertation toward the Iranian Board of Traditional Medicine. Authors of this article wish to express their thanks to Shahid Beheshti Medical University, Tehran, Iran to support the work and to Dr. Ali Sahraian for his assistance to choose the appropriate instrument.
Author Contributions
MP introduced the concept of this trial and design, contributed in data gathering and data analysis, prepared the draft, and revised the final version of article. RC introduced the design, contributed in writing the draft and revision of final version of the article. MRF contributed in data gathering and revision of final version of article. MMZ contributed in writing the draft and revision of final version of the article. PJ contributed toward data analysis and revision of final version of the article. The other coauthors contributed toward the guidance, revision, and correction of the article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval
This study was approved by the ethics committee of Shahid Beheshti Medical University, Tehran, Iran.