Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

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Journal of Ayurveda and Integrative Medicine

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Efficacy of ayurveda medications, Brahmi vati and Saraswatarista, in

generalized anxiety disorder- a randomized controlled trial
Varsha B. Gonugade a , Sameeran S. Chate b, Basavaraj R. Tubaki c,*, Rajat Thakur c
a
Department of Kayachikitsa, BVVS Ayurved Medical College & Hospital Bagalkot, Karnataka, India. 587101
b
Department of Psychiatry, J N Medical College, A Constituent Unit of KLE Academy of Higher Education & Research, Belagavi, Karnataka, India, 590016
c
Department of Kayachikitsa, Shri BMK Ayurveda Mahavidyalaya, A Constituent Unit of KLE Academy of Higher Education & Research, Belagavi, Karnataka, India,
590003

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Ayurvedic intervention (Brahmi Vati with Saraswatarista) is explored for their possible role in
Generalized anxiety disorder management of Generalized Anxiety Disorder (GAD), a common psychiatric disorder.
Brahmi vati Objective: The objective of the study was to evaluate the efficacy of Brahmi Vati and Saraswatarista in GAD.
Saraswatarista
Methods: Study is a randomized controlled clinical trial. Patients (n = 50) of GAD (Diagnostic and Statistical
Escitalopram
Ayurveda
Manual of Mental Disorders (DSM-5 criteria), 18–60 years of age, either sex participated in the study. Partici­
Randomized controlled trial pants were randomly divided into two groups. Group A, received escitalopram 10 mg/day for first 10 days
followed by 20 mg/day for next 50 days. Group B, received Ayurvedic intervention (Brahmi Vati 500 mg thrice a
day (TID) and Saraswatarista 10 ml TID) for 60 days. Assessments were with clinical parameters like Hamilton
Anxiety Rating Scale (HARS), GAD 7 scale (GAD 7), Beck Depression Inventory scale (BDI), Epworth sleepiness
scale (ESS), Pittsburgh Sleep Quality Index (PSQI), WHO Quality of Life- BREF (WHOQOL-BREF), Clinical Global
Improvement scale (CGI) and UKU-Side effect scale (UKU). These clinical assessments were measured on every
15th day during the intervention. Haemoglobin, liver function test (LFT), serum creatinine, serum urea were
assessed before and after the study.
Results: Study results indicate that both the groups were comparable in HARS, GAD7, BDI, WHOQOL-Bref and
CGI-Severity. Group B was better in PSQI (standard mean difference = 0.87, 95% CI: 0.28, 1.43), ESS (standard
mean difference = 1.42, 95% CI: 0.78, 2.02), CGI [global improvement (standard mean difference = 0.82, 95%
CI: 0.23,1.28) and efficacy index (standard mean difference = 0.97, 95% CI: 0.37,1.54)] and had better adverse
events profile (standard mean difference = 0.79, 95% CI: 0.21, 1.36). Both the groups had a good safety profile
assessed through liver and renal profiles.
Conclusion: Ayurveda interventions has additional advantages likes improvements in sleep profile, lesser adverse
events and better global improvement in management of GAD.
CTRI Registration Number is CTRI/2020/09/027750.

1. Introduction rate of remission and recovery [3].

Epidemiological study [4] on general population across 26 countries
Anxiety disorders are the most common mental illnesses worldwide showed that the lifetime prevalence of GAD in 12-month, 30-day were
and are associated with high comorbidity and mortality [1]. Generalized 3.7%, 1.8% and 0.8% across the globe respectively. GAD affects women
Anxiety Disorder (GAD) is one of the prevalent, severe, and incapa­ twice as frequently as it does men. Risk factors include low socioeco­
citating illnesses that is frequently misdiagnosed and undertreated. The nomic status, widowed, separated, divorced, middle age, comorbid
core feature of GAD is worry which is excessive, chronic, pervasive, and psychiatric disorders [5], history of substance abuse [6], trauma [7] and
is associated with physical, psychological symptoms that interferes with family history of GAD [8]. GAD symptomatology varies in severity. GAD
daily life [2]. It is marked by chronic course, high comorbidity, with low is associated with sleep disturbance in 60–70% of the patients [9]. A

Peer review under responsibility of Transdisciplinary University, Bangalore.

* Corresponding author.
E-mail address: ayurbasavaraj@[Link] (B.R. Tubaki).

[Link]
Received 2 November 2023; Received in revised form 28 June 2024; Accepted 5 July 2024
0975-9476/© 2024 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciences and Technology and World Ayurveda
Foundation This is an open access article under the CC BY-NC-ND license ([Link]
V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

systematic review [10]assessed humanistic and economic outcomes 2.2. Patients

among GAD patients and reported gross derangement in quality of life
affecting psychosocial functioning, role function, work productivity and Patients attending the out patient department of KLE’s Shri B M K
more disability days. Ayurveda Hospital Karnataka, India were recruited in the study.
GAD is diagnosed correctly in one third of the cases [11], 60 % of Reporting was as per CONSORT statement guidelines [22].Patients (n =
those diagnosed are not treated [12]. GAD is managed through various 50) diagnosed as Generalized Anxiety Disorder as per Diagnostic and
pharmacological agents. First line psychopharmacological agents are Statistical Manual of Mental Disorders (DSM-5) criteria [23] were
selective serotonin reuptake inhibitor (SSRI) and selective norepineph­ recruited from outpatient department of the Institute.
rine reuptake inhibitor (SNRI) and second line are buspirone, benzo­
diazapines, pregabalin and second generation antipsychotics [13]. A 2.2.1. Inclusion criteria
systematic review showed the efficacy of escitalopram over placebo with Patients of 18–60 years age of either sex. Patients with predominant
a good acceptability [14]. Few of the demerits with the current phar­ anxiety and worry for more than 6 months and meeting the other DSM-5
macological interventions include, a four-week wait for symptom alle­ diagnostic criteria for GAD were included in the study.
viation, lack of response, incomplete remission, lingering symptoms,
side effects, dependence, tolerance, and relapse risk [15]. Various fac­ 2.2.2. Exclusion criteria
tors including adverse effects are responsible for treatment seeking in Patients with lakshanas of Unmad (co-morbid psychiatric disorders);
complementary and alternative systems and anxiety forms the strongest on psychotropic drugs four weeks prior to study; substance abuse like
factor [16]. alcohol etc.; significant depression (BDI >17); other medical complica­
Ayurveda is one of the most ancient systems of medicine and has tions like hypertension, diabetes mellitus; pregnant and lactating
documented various treatment modalities for the management of psy­ women were excluded from the study.
chiatric disorders. ‘Chittodwega’ [17] mentioned in ayurvedic literature
resembles manifestations of GAD. It is primarily caused by derangement 2.2.3. Screening methods
of manasika doshas i.e., Rajas and Tamas. Brahmi Vati [18] and Sar­ Study brochures, pamplets, information were displayed at the
aswatarista [19] are together used by ayurvedic experts for the man­ prominent places of the hospital, institute, and in the camps conducted
agement of mental illnesses like GAD. A study [20] has showed that by the institute. Information brochures were circulated in various social
Brahmi Vati was effective in GAD. Escitalopram is one among SSRIs media platforms connecting physicians, rural health workers, patients
approved by United States Food and Drug Administration authority for and care givers visiting psychiatric unit of the hospital. VBG and BRT
the management of GAD [16]. Brahmi vati is a herbo mineral compound was responsible for these activities and personally communicated to all
formulation and has various ingredients like Brahmi (Bacoppa monnieri the information seekers. Patients meeting the diagnostic criteria of GAD
(L.) Pennell), Shankhapushpi (Convolvulus pluricaulis Choisy), Vacha (DSM-5) were screened to enrol 50 patients in the study. Patients were
(Acorus calamus), Swarnamakshika (Chalcopyrite), Rasa sindoora (Red recruited in the study were subjected to thorough examination and
sulphide of mercury) and Jatamamsi (Nardostachys jatamamsi. DC) etc. systematic data recording was done. Laboratory investigations including
[Table no 4 (supplementary data)]. Saraswatarista is an herbo-mineral haemoglobin, liver function test, serum creatinine and serum urea were
hydro alcoholic formulation with 22 ingredients. Ingredients are carried out in the clinical laboratory of the institute at baseline in all the
Brahmi, shatavari (Asparagus racemosus Willd), vidarika (Pueraria tuberosa patients.
(Willd.)DC), Amrita (Tinospora cordifolia Willd.), Vacha (Acorus calamus
Linn.), Ashwagandha (Withania somnifera (L.)Dunal) etc. [Table no 5 2.2.4. Intervention
(supplementary data)]. Brahmi Vati and Saraswatarista on co adminis­ All the patients were randomly divided into two interventional
tration has shown favourable outcome in our clinical settings. Hence this groups: Group A and Group B. Group A received Tab escitalopram 10
study was planned to compare the efficacy of Brahmi Vati along with mg/day for first 10 days, followed by 20 mg/day for next 50 days along
Saraswatarista in management of GAD. with water after food. Group B received Brahmi Vati 500 mg thrice a day
(TID) and Saraswatarista 10 ml TID after food with water for 60 days.
2. Materials and methods Dosage of the drugs were as per the classical text books of Ayurveda [21,
22].
2.1. Research design Ingredients of Brahmi vati and Saraswatarista were purchased from
reliable suppliers. All raw ingredients were authenticated at the Ministry
The study was a randomised controlled parallel group design. of AYUSH-approved Ayurveda, Siddha, and Unani (ASU) drug testing
Randomization was done using a block design with 25 blocks of 2. facility, Central Research Facility (CRF), Karnataka Lingayat Education
Online software (Random Number Generator software) was used for society (KLE) Shri B M Kankanwadi (BMK) Ayurveda Mahavidyalaya
random sequence generation. The sequences were created by the prin­ Belagavi. Each raw material and completed product underwent a qual­
cipal investigator and sealed. Allocations concealment was through itative analysis in accordance with API (Ayurvedic Pharmacopeia of
sealed opaque envelopes and were investigators blind. An impartial India) standards. Saraswatarista was prepared in the GMP certified KLE
assistant from the research unit who was not involved in patient allo­ Ayurveda pharmacy, Belagavi, Karnataka. Standard operating proced­
cation unsealed the envelopes one by one after each patient gave their ures were used in preparation of saraswatarista. Escitalopram was pro­
consent for the study and baseline assessment. The patients allocation in cured from Intas Pharmaceuticals Ltd. Ahmedabad Gujarat India (Batch
control and intervention groups were in the 1:1 ratio. Randomization, No. N2003251) complying the standard procedures. Duration of inter­
distribution, and administration of study-related materials were carried vention was 60 days with follow-up on every 15th day during treatment.
out by an independent research team. Adherence charts and counting of Patients were explained the nature and design of the study and
unused medications were noted to score the adherence. Assessment informed consent was obtained. The study was approved by the Insti­
through clinical assessment tools was conducted on every 15th day. tutional Ethics Committee (Protocol Id- BMK/19/PG/KC/3). CTRI
Laboratory parameters were evaluated at pre and post study. Registration Number is CTRI/2020/09/027750. Data collection was
Sample size calculation was based on a previous study [21]. And from February 2021 to June 2022. Patients were urged to follow the
calculation was through the primary outcome of this study (Standard treatment plan throughout the study and notify the researchers on
deviations were 3.23 and 4.28 in two groups, estimated effect size was development of any untoward events. A drug compliance chart was used
0.79). Total sample was 50, 25 in each arm with 5% alpha error, 80% to evaluate drug compliance and was given to the patient at each
power. appointment. It was instructed to fill it on daily basis, periodically send

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V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

it to the investigator (VBG) and submit the compliance chart during the assessments were foreign matter, ash values, water and alcohol extrac­
follow up visit. Unused drugs during the follow up visits were collected tive values and loss on drying. Rasa sindhur (reddish brown colour, taste
and cross checked with the adherence chart. less, odour less, test for mercury-present, test for sulphur-present),
swarna makshika bhasma (dark brown colour, taste less, loss on dry­
2.3. Criteria for assessment ing- 0.1%, acid soluble ash- 20.85%, qualitative test for iron-present).
Finished product details are furnished. Macroscopic description is,
2.3.1. Primary outcome measure tablet form, reddish brown colour and odourless. Physicochemical
Hamilton Anxiety Rating Scale (HARS) [24]. Is a 14 item clinician standards are loss on drying at 110 Centigrade was 3.05%, ash value was
administered clinical scale to asses the severity of anxiety. Scores of less 23.18%, acid insoluble ash was 14.02%, water soluble extractive was
than 17 indicates mild anxiety, moderate from 18 to 24 and severe 29.12%, alcohol soluble extractive was 25.44%, disintegration time was
anxiety is above 25. 20 min. Microbial test report (total bacterial count- 07 cfu/ml, total
fungal count- 01 cfu/ml), bacteria like [Link], [Link], [Link], S.
2.3.2. Secondary outcome measure abony were absent. Impression of the sample was of standard quality.
The secondary outcomes measures were GAD 7 scale [25] (Is a self
reported seven item measure that evaluates main manifestations of 3.1.2. Saraswatarista
GAD. Low anxiety ranges from 0 to 4, mild anxiety from 5 to 9, moderate Qualitative analysis of each raw herbal drugs were macroscopic
anxiety from 10 to 14, and severe anxiety above 15). Beck’s Depression assessment (part, color, taste, odour). Physico chemical assessments
Inventory scale (BDI) [26] (is a self-reported, 21-item rating scale used were foreign matter, ash values, water and alcohol extractive values,
to assess depressive symptoms. Total score of 0–13 is minimal depres­ loss on drying, organoleptic characters were -liquid form, dark brown
sion, 14–19 is mild, 20–28 is moderate and 29–63 is severe depression), colour, fragrant odour and bitter taste. Physico chemical standards are
Epworth sleepiness scale (ESS) [27] (Is a 8 item scale measuring the day specific gravity 1.10 g, total solids were 25.98% W/V, reducing sugars
time sleepiness. Scores 0–5 is lower normal, 6–10 higher normal, 11–12 were 12.5%, alcohol content was 10% V/V and pH value was 3.57.
mild excessive, 13–15 moderate excessive, 16–24 is severe excessive Microbial test report (total bacterial count- 09 cfu/ml, total fungal
daytime sleepiness), Pittsburgh Sleep Quality Index (PSQI) [28] (Is a 19 count- 03 cfu/ml), bacteria like [Link], [Link], [Link], [Link]
item self rated questionnaire assessing sleep quality and sleep distur­ were absent. Impression of the sample was of standard quality.
bance. Scores above 5 suggest of sleep disturbance), World health
organisation (WHO) Quality of Life- BREF (WHOQOL-BREF) [29] (Is a 3.2. Patient profile
26 item self reported questionnaire assessing quality of life in domains
like physical health, psychological health, social relationships, and Sixty five patients meeting the diagnostic criteria (DSM-5) of GAD
environment), Clinical Global Improvement scale (CGI) [30] (Is a 3 item were screened. Not meeting the criteria were 10 due to significant co­
observer rated clinical tool assessing severity of symptoms, treatment morbidity like depression, concomitant disease like diabetes mellitus.
response and efficacy of treatments), UKU-side effect scale [31] (Is a 48 Five patients meeting the criteria declined to participate in the study.
items global assessment of side effects for psychotrophic drugs assessing Reasons were apprehensions related to clinical trial, unable to comply
in domains like psychic, autonomic, neurological and others). Haemo­ with the protocol like frequency of visits, regularly filling the drug
globin, serum creatinine, serum urea, liver function tests (total bilirubin, compliance forms etc. A total of 50 patients participated in the study. No
direct bilirubin, aspartate amino transferase, alanine amino transferase, patient dropped out of the study. The base line features like mean age (p
alkaline phosphatase, total protein and albumin, albumin/globulin = 0.37), gender (p = 0.22), educational status (p = 0.94), marital status
ratio) were the blood parameters. All the clinical assessment scales were (p = 0.30), diet status (p = 0.55), Shareerika prakurti (p = 0.60),
evaluated at baseline, 15th, 30th, 45th, and 60th day. Blood assessments manasika prakurti (p = 0.66), weight (p = 0.63), BMI (p = 0.59),
were done at base line and 60th day of interventions. duration of illness (p = 0.66), systolic blood pressure (p = 0.61), dia­
stolic blood pressure (p = 0.48) were comparable between the groups
2.4. Statistical methods except socio-economic status (p = 0.006). Most of the base line clinical
features like HARS (p = 0.93), GAD7 (p = 0.79), BDI (p = 0.50), PSQI (p
SPSS Version 25.0 (IBM Corporation, Chicago, Illinois, United States) = 0.11), WHOQOL-Bref (p = 0.16), CGI severity (p = 0.33) were com­
was used for the statistical analysis. By the χ2 test, the homogeneity parable between the groups except ESS (p = 0.01) (Table 1) (Fig. 1).
between groups was assessed. A two-way repeated measure analysis of Blood parameters including haemoglobin, liver function test, serum
variance (rmANOVA) with a Bonferroni post-hoc test was used to creatinine and serum urea were comparable between the groups at
compare the groups at different time intervals. Two time points within baseline.
the same group were compared using the paired t-test. The independent
sample t-test was used to compare the groups at a given time point. By 3.3. Primary outcome
comparing pre- and post-treatment changes, the treatment outcome was
evaluated. The treatment effect was measured by the outcome from HARS Assessments showed that outcomes were comparable between
baseline to the 60th day of the intervention and the effect size was both the groups (p = 0.08). Both the groups showed significant
calculated using the partial Eta Square method. Effect size measure­ improvement in HARS at all the five time points (p < 0.001). Effect size
ments were interpreted as follows: 0–0.2 minimal, 0.2–0.5 small, was minimal (standard mean difference = 0.06, CI: 0.50, 0.61). [Table 2
0.5–0.8 medium, and above 0.8 high effect size [32]. Reporting values is (supplementary data),].
done as mean ± standard deviation. Statistical significance was set at p
< 0.05. 3.4. Secondary outcomes

3. Results 3.4.1. Between group comparison

Between group comparison of outcomes in PSQI (p = 0.003), CGI-G
3.1. Characterization of medicines (p = 0.006), CGI-E (p = 0.001) and UKU (p = 0.005) showed significant
difference and outcomes of group B were better than group A. In pa­
3.1.1. Brahmi vati rameters of GAD7 (p = 0.33), BDI (p = 0.05), WHOQOL-Bref (p = 0.11)
Qualitative analysis of each raw ingredients of the herbal drugs were and CGI-Severity no significant difference in outcomes were observed
macroscopic assessment (part, color, taste, odour). Physico chemical between groups. ESS (p < 0.001) showed significant difference between

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V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

Table. 1 3.4.3. Effect size

Patient profile at baseline. Effect size showed large effect in PSQI (standard mean difference =
Clinical profile Group A (n Group B (n p 0.87, 95% CI: 0.28, 1.43), ESS (standard mean difference = 1.42, 95%
= 25) = 25) CI: 0.78, 2.02), CGI- Global improvement (standard mean difference =
Age (Yrs) 33.52 ± 30.96 ± 0.37 0.82, 95% CI: 0.23,1.28) and CGI-Efficacy index (standard mean dif­
11.22 8.69 ference = 0.97, 95% CI: 0.37,1.54)]. And was of medium effect in UKU
Gender Male 14 6 0.22
side effect scale (standard mean difference = 0.79, 95% CI: 0.21, 1.36).
Female 11 19 Effect size was small in GAD7 (standard mean difference = 0.33, 95% CI:
Socioeconomic Higher class 6 14 0.006 − 0.23, 0.88), WHOQOL-Bref (standard mean difference = 0.45, 95% CI:
Status Middle class 15 8 − 0.11, 1.01), BMI (standard mean difference = 0.22, 95% CI: − 0.34,
Lower class 4 3
0.77), DBP (standard mean difference = 0.20, 95% CI: − 0.36, 0.77) and
Diet Vegetarian 8 10 0.55
Non vegetarian 17 15 minimal in HARS (standard mean difference = 0.06, 95% CI: − 0.50,
Education status Primary 5 5 0.94 0.61),BDI (standard mean difference = 0.05, 95% CI: − 0.51, 0.60), SBP
High school 8 7 (standard mean difference = 0.09, 95% CI: − 0.46, 0.65), CGI-S (stan­
Graduate 12 13 dard mean difference = 0, 95% CI: − 0.55, 0.55) and weight (standard
Marrital Status Married 11 10 0.30
Unmarried 12 15
mean difference = 0, 95% CI: − 0.55, 0.55).
Widow 2 0
Shareerika Vata 2 0 0.60 3.4.4. Adverse effects
Prakurti Kapha Vata 3 3 Mild adverse effects noted in 13 patients of group A. UKU side effect
Pitta Kapha 3 3
scale assessment showed autonomic side effects 2 (giddiness), psychic
Vata Kapha 2 1
Vata Pitta 15 18 side effects 2 (sleepiness, lethargy, fatigue). Group B showed adverse
Manasika Prakurti Rajasika 21 23 0.66 effects in 3 patients and they were psychic side effects 2 (sleepiness) and
Tamasika 4 2 other forms was 1 (reduced appetite). Chi square test comparing number
Base line HARS 23.56 ± 23.40 ± 0.93 of adverse events between group showed significant higher adverse
characteristics 6.12 6.84
GAD7 14.96 ± 15.12 ± 0.79
events in group A than group B (p = 0.006). UKU global assessment
2.03 2.22 showed physician and patient assessment scores as 2 in psychic side
BDI 12.84 ± 13.40 ± 0.50 effects. In other form of side effects, physician assessment was 1 and
3.14 2.71 patient assessment was 2. Adverse events were mild to moderate cate­
ESS 5.44 ± 7.28 ± 0.01
gory and occurred during the different time points of the interventions,
3.01 1.84
PSQI 10.44 ± 8.92 ± 0.11 not affected the functioning of the patients and needed no additional
3.33 3.44 intervention.
WHOQOL-Bref 91.28 ± 88.52 ± 0.16 Comparison of groups in terms of different time points showed that
6.93 6.81 group B produced significant effects from 30th day of intervention, as
CGI-S 3.48 ± 3.64 ± 0.33
0.59 0.57
CGI-G showed changes at 30th day (p = 0.04), 45th day (p < 0.001) and
Weight (Kgs) 57.92 ± 59.17 ± 0.63 60th day (p = 0.001). Due to adverse events related to sleep and day
9.68 9.04 time drowsiness, significant differences were noted from 15th day on­
BMI 22.68 ± 23.2 ± 0.59 wards. PSQI showed significant difference at 15th day (p = 0.05), 30th
3.06 3.72
day (p < 0.001), 45th day (p < 0.001) and 60th day (p < 0.001). ESS
Systolic Blood 122.8 ± 121.6 ± 0.61
pressure (mm of Hg) 10.21 6.24 showed changes at 30th day (p = 0.01), 45th day (p = 0.007) and 60th
Diastolic Blood 79.60 ± 78.8 ± 0.48 day (p = 0.02). CGI-E showed changes in all time points, 15th day (p =
pressure (mm of Hg) 4.54 3.77 0.03), 30th day (p = 0.001), 45th day (p < 0.001) and 60th day (p <
Duration of illness (Yrs, mean ± SD) 2.44 ± 2.2 ± 1.7 0.66 0.001).
2.05
Laboratory parameters like haemoglobin, total bilirubin, direct
Study completed 25 25 ​
bilirubin, AST, ALT, Total protein, albumin, AG ratio, alkaline phos­
Data are expressed in Mean and/or standard deviations (S.D.). HARS-Hamilton phatase, serum creatinine, serum urea were within normal limit in both
Anxiety Rating scale, GAD7- Generalized Anxiety disorder 7 scale, BDI- Beck’s the groups, pre and post intervention (Table 3, supplementary data).
Depression Inventory scale, ESS-Epworth sleepiness scale, PSQI- Pittsburgh
Sleep Quality Index, WHOQOL-BREF- WHO quality of life -BREF, CGI- Clinical
Global Impression scales, BMI-Body Mass Index. UKU- UKU Side effect scale. 4. Discussion

The study demonstrated that the effect of Ayurveda interventions

groups, however ESS scores increased in group A and trend of decrease
(Brahmi vati and Saraswatarista) were comparable to escitalopram.
were noted in group B.
Both the interventions produced comparable outcomes in anxiety,
depression, quality of life and disease severity (HARS, GAD7, BDI,
3.4.2. Within group comparison
WHOQOL-Bref and CGI-Severity). Ayurveda interventions showed
Within group assessment showed that in both the groups significant
significantly better outcome improvements compared to escitalopram in
improvements were noted in most of the time points in GAD7 (p <
night sleep, global improvement and efficacy index (PSQI, CGI-G and
0.001), BDI (p < 0.001), PSQI (p < 0.001), WHOQOL-Bref (p < 0.001),
CGI-E). Escitalopram showed significant worsening of adverse events
CGI-S (p < 0.001). CGI-G scores showed significant improvements on
profile and day time sleepiness (UKU and ESS) compared to ayurveda
45th day [group A (p = 0.007), group B (p < 0.001)] and 60th day (p <
group. However Ayurveda groups showed trends of decrease in day time
0.001) in both the groups. CGI-E scores showed significant improve­
sleepiness and lesser adverse events profile. Mild adverse events were
ments on all time points of group B and in group A, it was only at 45th
more frequent in escitalopram group (13 patients) compared to ayur­
day (p = 0.008) and 60th day (p < 0.001). ESS and UKU scores showed
veda group (3 patients). Both the interventions showed good safety
significant increase in all time points of group A and no such changes
profile as liver function tests, serum creatinine, serum urea and hae­
were observed in group B. (Table 2, Supplementary data).
moglobin levels were within the normative ranges at both pre and post
assessments.
Review of patient profile in the study showed that more patients

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V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

Fig. 1. Subject flow chart through the study.

were middle age (32.24 yrs),female gender (60%), mean duration of (60th day) in both the groups.
illness was 2.32 yrs, weight (58.54 kgs), BMI (22.94), moderate (HARS- Similar to our study, a flexible dose of escitalopram (10–20 mg/day)
23.4) to severe anxiety (GAD7-15), mild to moderate depression for 8 weeks showed to be safe, effective and well tolerated in patients of
(13.12), severity was mildly ill (CGI-S- 3.56), normal day time sleepiness GAD [33]. A study [34] with a pooled data from double blind placebo
(ESS- 6.36) and disturbed night sleep (PSQI -9.68). controlled trials with 850 patients showed that escitalopram (10 mg/day
Effect of escitalopram and ayurveda interventions were comparable in first 4 week and 20 mg/day in next 4 weeks) was effective and well
in primary outcome (HARS). Both the groups had comparable im­ tolerated in GAD and observed side effects were nausea, ejaculation
provements in few of the secondary outcomes like GAD7, BDI, disorder, fatigue, insomnia, decreased libido, and anorgasmia. Most
WHOQOL-Bref and CGI-Severity. Within group comparison showed that common adverse effect was fatigue or somnolence in our study and
both groups produced significant and similar improvements in HARS, similar finding is also reported [35].
GAD7, BDI, WHOQOL-Bref and CGI-Severity. Ayurveda interventions A clinical study showed that Brahmi vati was effective in patients of
produced better outcomes in PSQI, CGI-G and CGI-E. Escitalopram GAD and it decreased anxiety and depression, improved disturbed sleep
showed significant higher adverse events profile (UKU) compared to and quality of life and was comparable to Manasamitra vataka (a com­
ayurveda group. Adverse event profile in escitalopram showed signifi­ pound herbo mineral ayurveda formulation available in tablet form)
cant worsening at different time points. Day time sleepiness scores (ESS) [23]. These findings are similar to our current study. Another study [36]
were significantly high in escitalopram group and it worsened at showed that Brahmi vati reduced anxiety and improved sleep profiles in
different time points, though they were in the normative ranges. Systolic patients of essential hypertension. Saraswatarista has various ingredients
and diastolic blood pressures were within the normative ranges in both with anxiolytic, nootropic, antioxidant properties and produced
the groups during the entire study and showed no significant changes. decreased immobility in forced swim test and absence of general stim­
Weight and BMI showed no significant changes with both the in­ ulation in open field test, suggestive of antidepressant activity [37] in
terventions. Liver function tests, serum creatinine, serum urea and animal model. Brahmi has stress-relieving and antioxidant properties. It
haemoglobin levels were within normative ranges in both the inter­ also lowers lipid peroxidation in the rat prefrontal cortex, hippocampus
ventional groups. Ayurveda group showed better global improvements and striatum and helps in the repair of abnormalities in neurotrans­
(CGI-GI) and efficacy (CGI-E), this could be due to better adverse effect mission and has antidepressant properties [38]. Shankhpushpi has
profiles in ayurveda group. Effect size was large in ESS, PSQI, CGI-GI, anxiolytic, antidepressant, antioxidant, hypolipidemic, tranquillizing,
CGI-E and medium in UKU side effect scale favouring Ayurveda group. antistress, immunomodulatory and analgesic activity [39]. Increase in
Anxiety levels decreased from moderate-severe (HARS, GAD7) to mild brain monoamine and GABA neurotransmitter, anxiolytic effects were
category. Depression (BDI) reduced from mild to moderate category to noted with Jatamamsi (Nardostachys jatamansi) [40]. Guduchi (Tinospora
minimal depression in both the groups. Day time sleepiness scores were cordifolia) counteracts the depressive-like behaviour in mice and
within the normative ranges in both the groups. Night sleep disturbance decreased the brain’s monoamine oxidase activity, which led to higher
reduced from disturbed levels to normal ranges in ayurveda group and concentrations of brain monoamines [41]. Other studies have also
remained disturbed in escitalopram group. Clinical global impressions- demonstrated the effect of Ayurveda interventions in GAD. A study [26]
severity scores reduced from mild to border line ill category in both showed that effect of Manasamitra vataka was comparable to clonaze­
the groups. Clinical global impressions-global improvements progressed pam in GAD with comorbid social phobia and it reduced anxiety,
from minimally improved (15th day) to much improved scores (60th depression and improved quality of life. It also showed that add on effect
day) in both the groups. Clinical global impressions-efficacy index of shirodhara (ayurveda therapy of oil dripping on forehead) with Brahmi
progressed from minimal (15th day) to moderate therapeutic effect taila (Ayurveda medicated oil) was helpful in reduction of daytime

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V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

Table. 2
Effects on outcome variables.
Sr Parameter Interven Baseline 15th day 30th day 45th day 60th day Outcome difference P value Effect
No tion (0–60day) size

​ Primary Outcomes ​
1. HARS A 23.56 ± 6.12 21.16 ± 15.84 ± 12.16 ± 10.08 ± 4.25 13.68 ± 3.76 0.84 0.06
5.12 4.26 3.97
B 23.40 ± 6.84 20.84 ± 16.36 ± 12.08 ± 9.72 ± 4.24 13.48 ± 3.30
5.98 5.43 5.16
​ Secondary outcomes ​
2. GAD-7 A 14.96 ± 2.03 12.20 ± 8.92 ± 1.71 7.12 ± 1.88 5.84 ± 1.65 8.68 ± 1.62 0.30 0.33
1.96
B 15.12 ± 2.22 12.76 ± 9.80 ± 2.12 7.68 ± 2.08 6.44 ± 1.61 9.12 ± 1.36
2.26
3. BDI A 12.84 ± 3.14 11.64 ± 10.00 ± 6.88 ± 1.90 5.16 ± 2.43 7.8 ± 2.48 0.87 0.05
2.86 2.45
B 13.40 ± 2.71 12.60 ± 10.88 ± 7.32 ± 2.21 5.60 ± 1.63 7.68 ± 2.77
2.60 2.30
4. ESS A 5.44 ± 3.01 8.56 ± 3.07 9.08 ± 2.52 8.84 ± 2.32 8.40 ± 2.38 − 2.96 ± 2.30 <0.001 1.42
B 7.28 ± 1.84 7.56 ± 2.14 7.20 ± 2.08 7.04 ± 1.95 6.92 ± 1.89 0.36 ± 1.18
5. PSQI A 10.44 ± 3.33 10.40 ± 8.88 ± 3.15 8.04 ± 2.86 8.04 ± 3.02 2.4 ± 1.87 0.003 0.87
3.14
B 8.92 ± 3.44 8.64 ± 3.23 6.20 ± 2.53 5.20 ± 2.24 4.64 ± 1.98 4.28 ± 2.42
6. WHO-QOL- A 91.28 ± 6.93 92.32 ± 96.32 ± 99.52 ± 101.08 ± − 8.36 ± 2.94 0.11 0.45
BREF 7.00 7.10 7.30 7.04
B 88.52 ± 6.81 89.60 ± 92.08 ± 95.04 ± 96.88 ± 5.61 − 9.80 ± 3.39
6.49 6.36 6.25
7. CGI-S A 3.48 ± 0.59 3.12 ± 0.44 2.60 ± 0.58 2.24 ± 0.44 2.16 ± 0.37 1.32 ± 0.47 1 0
B 3.64 ± 0.57 3.32 ± 0.56 2.80 ± 0.50 2.64 ± 0.57 2.32 ± 0.48 1.32 ± 0.47
8. CGI-GI A – 3.08 ± 0.28 2.84 ± 0.37 2.36 ± 0.49 1.92 ± 0.49 0.8 ± 0.5 0.006 0.82
B – 3.20 ± 0.41 3.00 ± 0.00 2.84 ± 0.37 2.40 ± 0.50 1.16 ± 0.37
9. CGI-E A – 9.16 ± 0.80 8.04 ± 1.74 5.64 ± 1.50 5.16 ± 0.80 2.72 ± 1.86 0.001 0.97
B – 9.96 ± 1.67 9.68 ± 1.03 8.36 ± 2.38 7.24 ± 2.35 4±0
10. UKU A – 0.28 ± 0.45 0.52 ± 0.50 0.48 ± 0.50 0.48 ± 0.50 − 0.48 ± 0.50 0.005 0.79
B – 0 0.04 ± 0.20 0.12 ± 0.33 0.12 ± 0.33 − 0.12 ± 0.33
​ Clinical assessment ​
11. Weight (Kgs) A 57.92 ± 9.68 57.83 ± 9.7 57.91 ± 58.06 ± 58.11 ± 9.84 − 0.19 ± 5.96 1 0
9.61 9.82
B 59.17 ± 9.04 59.27 ± 59.42 ± 59.37 ± 59.37 ± 9.01 − 0.19 ± 0.71
8.99 8.91 8.97
12. BMI A 22.68 ± 3.06 22.64 ± 22.03 ± 22.08 ± 22.1 ± 5.07 0.58 ± 3.38 0.35 0.22
3.07 5.02 5.05
B 23.2 ± 3.72 23.26 ± 23.29 ± 23.62 ± 23.25 ± 3.71 − 0.05 ± 0.29
3.70 3.67 3.69
13. SBP (mm of A 122.8 ± 121.6 ± 121.6 ± 121.6 ± 122 ± 8.66 0.8 ± 4.93 0.74 0.09
Hg) 10.21 10.27 9.86 8.98
B 121.6 ± 6.24 120 ± 7.63 120.8 ± 118.8 ± 121.2 ± 5.25 0.4 ± 3.51
7.59 7.25
14. DBP (mm of A 79.60 ± 4.54 78.4 ± 4.72 79.2 ± 4.93 78 ± 4.02 78 ± 5.77 1.6 ± 6.88 0.25 0.20
Hg) B 78.8 ± 3.77 77.6 ± 4.35 76.80 ± 78 ± 5.77 79.2 ± 4.93 − 0.4 ± 5.38
4.76

Data are expressed in Mean and/or standard deviations (S.D.). HARS-Hamilton Anxiety Rating scale, GAD7- Generalized Anxiety disorder 7 scale, BDI- Beck’s
Depression Inventory scale, ESS-Epworth sleepiness scale, PSQI- Pittsburgh Sleep Quality Index, WHOQOL-BREF- WHO quality of life -BREF, CGI- S- Clinical Global
Impression - Severity, CGI- GI- Clinical Global Impression – Global Improvement, CGI- EI- Clinical Global Impression – Efficacy Index, BMI-Body Mass Index. UKU- UKU
Side effect scale, SBP- Systolic Blood Pressure, DBP- Diastolic Blood Pressure.

sleepiness. the better picture of the outcomes. Hence warrants multi centric study.
Socio-economic status was not comparable between the groups. Middle
class were more in escitalopram and lower class in Ayurveda group. This
4.1. Strengths of the study
could be limitation as socioeconomic status can effect the disease and
participants through factors like nutrition and environment. Assessment
Strengths of the study are randomized controlled parallel group
through the subjective parameters is the limitations of the study and
design, 60 days of intervention and gold standard control. Gross clinical
assessments through cortisol, electrophysiological parameters would
assessments like anxiety, depression, day time sleepiness, night sleep
have given more strength to the study. Study samples were of middle age
profile, quality of life, adverse effect profile, assessment of global
and further studies are needed to extrapolate to other populations.
improvement and efficacy index were helpful in better global assess­
Detailed assessment of Brahmi Vati and Saraswatarista through other
ments. Safety profile of the drugs assessed through liver function test,
qualitative phytochemical analysis like phytoestrogen assessment,
serum creatinine, serum urea and haemoglobin levels is also note
reverse phase- HPLC analysis, steroid estimation, HPTLC assessment etc
worthy component.
would have been beneficial. Drug to drug interaction between Brahmi
Vati and Saraswatarista needs to be studied. Ayurveda group showed
4.2. Limitations of the study improvement in sleep profile of GAD patients. A study in GAD patients
with sleep disturbance can through a more light on its utility. Addi­
Study has limitations. Though sample size was adequate to demon­ tionally, it is restricted to the regional and cultural populations of the
strate the statistical significance, larger population will help in viewing

6
V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

Table. 3 Declaration of generative AI in scientific writing

Effects on safety variables.
Sl. Outcome variable Intervention Baseline 60th day P Nothing to disclose.
No

1 Hemoglobin (g/dl) A 11.76 ± 12.02 ± 0.08 Author contributions

2.04 1.7
B 11.91 ± 11.8 ±
VBG - Methodology, Writing - Original draft preparation,Visualiza­
1.42 1.46
2 ESR (mm in 60 mints) A 18.1 ± 9.5 15.5 ± 1 tion, Data collection, Writing - Reviewing and Editing.
7.9 BRT - Conceptualization, Methodology, Writing - Original draft
B 17.5 ± 7.5 17.3 ± preparation, Writing -Reviewing and Editing, Statistical analysis.
7.1 SH - Methodology, Writing - Original draft preparation, Visualiza­
3 Total Bilirubin (mg/ A 0.4 ± 0.05 0.4 ± 0.82
tion, Data collection, Writing - Reviewing and Editing.
dL) 0.06
B 0.4 ± 0.03 0.4 ± RT - Visualization, Data collection, Writing - Reviewing and Editing.
0.05
4 Direct Bilirubin (mg/ A 0.1 ± 0 0.1 ± 0 1
Acknowledgements
dL) B 0.1 ± 0 0.1 ± 0.1
5 AST (IU/mL) A 22.9 ± 24.3 ± 0.03
5.08 8.6 We would like to thank the principal, staff and PG scholars of
B 23.3 ± 21.5 ± KAHER’s BMK Ayurveda Mahavidyalaya college and hospital for their
4.32 5.8 support.
6 ALT (IU/mL) A 24.4 ± 6.9 23 ± 5.5 0.33
B 25.9 ± 4.1 22.6 ±
6.4 Appendix A. Supplementary data
7 Albumin (mg/dL) A 4.05 ± 0.1 3.9 ± 0.1 0.01
B 3.9 ± 0.2 4.0 ± 0.1
Supplementary data to this article can be found online at [Link]
8 A/G ratio A 1.2 ± 0.1 1.2 ± 0.1 0.24
B 1.1 ± 0.1 1.1 ± 0.1 org/10.1016/[Link].2024.101033.
9 Total Protein (mg/dL) A 7 ± 0.2 7.1 ± 0.2 0.75
B 7.0 ± 0.2 7.0 ± 0.2
References
10 Alkaline Phosphatase A 119.3 ± 121.9 ± 0.22
(IU/mL) 17.2 13.7
B 121.6 ± 119.7 ± [1] Stein DJ, Scott KM, de Jonge P, Kessler RC. Epidemiology of anxiety disorders:
from surveys to nosology and back. Dialogues Clin Neurosci 2017;19(2):127–36.
16.2 9.6
[Link] PMID: 28867937; PMCID:
11 Serum Creatinine A 0.8 ± 0.1 0.8 ± 0.1 0.40
PMC5573557.
(mg/dL) B 0.8 ± 0.1 0.8 ± 0.8 [2] DeMartini J, Patel G, Fancher TL. Generalized anxiety disorder. Ann Intern Med
12 Serum Urea (mg/dL) A 22.5 ± 4.0 22.3 ± 0.33 2019;170(7):ITC49–64. [Link] PMID:
3.6 30934083.
B 22.6 ± 3.8 22.5 ± [3] Kelly KM, Mezuk B. Predictors of remission from generalized anxiety disorder and
3.4 major depressive disorder. J Affect Disord 2017;208:467–74. [Link]
10.1016/[Link].2016.10.042. PMID: 27863710; PMCID: PMC5515235.
ESR- Erythrocyte sedimentation rate, AST-Aspartate aminotransferase, ALT- [4] Ruscio AM, Hallion LS, Lim CCW, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J, et al.
Alanine transaminase, A/G-Albumin globulin ratio. Cross-sectional comparison of the Epidemiology of DSM-5 generalized anxiety
disorder across the globe. JAMA Psychiatr 2017;74(5):465–75. [Link]
10.1001/jamapsychiatry.2017.0056. PMID: 28297020; PMCID: PMC5594751.
study area. Long term follow up study will be beneficial. [5] Grant BF, Hasin DS, Stinson FS, Dawson DA, June Ruan W, Goldstein RB, et al.
Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV
5. Conclusion generalized anxiety disorder in the USA: results from the National Epidemiologic
Survey on Alcohol and Related Conditions. Psychol Med 2005;35(12):1747–59.
[Link] PMID: 16202187.
Current study showed that ayurveda drugs (Brahmi vati along with [6] Bolton JM, Sareen J. Lifetime mood, anxiety, and drug use disorders are common
saraswatarista) were comparable to escitalopram in management of in the United States population. Evid Base Ment Health 2006;9(4):113. [Link]
org/10.1136/ebmh.9.4.113. PMID: 17065310.
GAD by decreasing anxiety, depression, improving quality of life. Ay­ [7] Brawman-Mintzer O, Monnier J, Wolitzky KB, Falsetti SA. Patients with
urveda drugs showed advantages over escitalopram in improving night generalized anxiety disorder and a history of trauma: somatic symptom
sleep, decreasing day time drowsiness, better adverse effect profile, endorsement. J Psychiatr Pract 2005;11(3):212–5. [Link]
00131746-200505000-00010. PMID: 15920396.
better global improvement and efficacy index. Ayurveda drugs showed a [8] McLaughlin KA, Behar E, Borkovec TD. Family history of psychological problems in
better comprehensive improvements compared to escitalopram. Long generalized anxiety disorder. J Clin Psychol 2008;64(7):905–18. [Link]
term studies are needed to have a better picture of efficacy and adverse 10.1002/jclp.20497. PMID: 18509873; PMCID: PMC4081441.
[9] Papadimitriou GN, Linkowski P. Sleep disturbance in anxiety disorders. Int Rev
events profiles. Further studies are needed to understand the pharma­
Psychiatr 2005;17(4):229–36. [Link]
cokinetic and pharmacodynamic properties of the ayurveda drugs. PMID: 16194794.
[10] Revicki DA, Travers K, Wyrwich KW, Svedsäter H, Locklear J, Mattera MS, et al.
Funding sources Humanistic and economic burden of generalized anxiety disorder in North America
and Europe. J Affect Disord 2012;140(2):103–12. [Link]
jad.2011.11.014. PMID: 22154706.
This research did not receive any specific grant from funding [11] Wittchen HU, Kessler RC, Beesdo K, Krause P, Höfler M, Hoyer J. Generalized
agencies in the public, commercial, or not-for-profit sectors. anxiety and depression in primary care: prevalence, recognition, and management.
J Clin Psychiatry 2002;63(Suppl 8):24–34. PMID: 12044105.
[12] Wang PS, Lane M, Olfson M, Pincus HA, Wells KB, Kessler RC. Twelve-month use of
Conflicts of interest mental health services in the United States: results from the National Comorbidity
Survey Replication. Arch Gen Psychiatr 2005;62(6):629–40. [Link]
10.1001/archpsyc.62.6.629. PMID: 15939840.
The authors declare that they have no known competing financial [13] Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for
interests or personal relationships that could have appeared to influence generalized anxiety disorder in adult and pediatric patients: an evidence-based
the work reported in this paper. treatment review. Expet Opin Pharmacother 2018;19(10):1057–70. [Link]
org/10.1080/14656566.2018.1491966. PMID: 30056792; PMCID: PMC6340395.
[14] Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological
treatments for generalised anxiety disorder: a systematic review and network meta-
analysis. Lancet 2019;393(10173):768–77. [Link]

7
V.B. Gonugade et al. Journal of Ayurveda and Integrative Medicine 15 (2024) 101033

(18)31793-8. Erratum in: Lancet. 2019 Apr 27;393(10182):1698. PMID: [29] The World Health Organization Quality of Life Assessment (WHOQOL).
30712879. Development and general psychometric properties. Soc Sci Med 1998;46(12):
[15] Katzman MA. Current considerations in the treatment of generalized anxiety 1569–85. [Link] PMID: 9672396.
disorder. CNS Drugs 2009;23(2):103–20. [Link] [30] Guy W, editor. ECDEU assessment manual for psychopharmacology. Rockville,
200923020-00002. PMID: 19173371. MD: US Department of Health, Education, and Welfare Public Health Service
[16] Astin JA. Why patients use alternative medicine: results of a national study. JAMA Alcohol, Drug Abuse, and Mental Health Administration; 1976.
1998 May 20;279(19):1548–53. [Link] [31] Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating
PMID: 9605899. scale. A new comprehensive rating scale for psychotropic drugs and a cross-
[17] Trikamji Y, editor. Charaka samhita of charaka, vimana sthana; Roganika sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand
vimanam. second ed. Varanasi: Chaukhabha Sanskrit series; 2017. p. 254 [chapter Suppl 1987;334:1–100. [Link]
6], verse 5. PMID: 2887090.
[18] Pathak R, Sara Sangraha Ayurveda, Prakarana Vati. Vol1,Varanasi. Chaukhamba [32] Cohen J. Statistical power analysis for the behavioral sciences. 2 ed. L. Erlbaum
Publication; 2009. p. 455–6. Associates; 1988.
[19] Mishra B, [Link] Lochan(English translation). Bhaisajya ratnavali of govind [33] Davidson JR, Bose A, Korotzer A, Zheng H. Escitalopram in the treatment of
dasji bhisagratna. Varanasi: Chaukhamba Publications; 2008. p. 1115. generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study.
[20] Khot SG, Tubaki BR, Gonugade VB. Efficacy of Brahmi vati in generalised anxiety Depress Anxiety 2004;19(4):234–40. [Link] PMID:
disorder - randomized double blind comparative clinical trial. J Ayurveda Integr 15274172.
Med 2022;13(2):100552. [Link] PMID: [34] Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with
35325682; PMCID: PMC8943402. escitalopram: pooled results from double-blind, placebo-controlled trials. J Affect
[21] Tubaki BR, Chandrashekar CR, Sudhakar D, Prabha TN, Lavekar GS, Kutty BM. Disord 2005;87(2–3):161–7. [Link] PMID:
Clinical efficacy of Manasamitra Vataka (an Ayurveda medication) on generalized 15982747.
anxiety disorder with comorbid generalized social phobia: a randomized controlled [35] Lenze EJ, Rollman BL, Shear MK, Dew MA, Pollock BG, Ciliberti C, Costantino M,
study. J Alternative Compl Med 2012;18(6):612–21. [Link] Snyder S, Shi P, Spitznagel E, Andreescu C, Butters MA, Reynolds CF 3rd.
acm.2010.0778. PMID: 22784349. Escitalopram for older adults with generalized anxiety disorder: a randomized
[22] Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 Statement: controlled trial. JAMA 2009;301(3):295–303. [Link]
updated guidelines for reporting parallel group randomised trials. BMC Med 2010 jama.2008.977. PMID: 19155456; PMCID: PMC2840403.
Mar 24;8:18. [Link] PMID: 20334633; PMCID: [36] Mishra D, Tubaki BR. Effect of Brahmi vati and Sarpagandha Ghana vati in
PMC2860339. management of essential hypertension - a randomized, double blind, clinical study.
[23] American Psychiatric Association, DSM-5 Task Force. Diagnostic and statistical J Ayurveda Integr Med 2019;10(4):269–76. [Link]
manual of mental disorders: DSM-5™. fifth ed. American Psychiatric Publishing, jaim.2017.04.001. PMID: 29242090; PMCID: PMC6938844.
Inc.; 2013. [Link] 2013. [37] Parekar RR, Jadhav KS, Marathe PA, Rege NN. Effect of Saraswatarishta in animal
[24] Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959;32 models of behavior despair. J Ayurveda Integr Med 2014;5(3):141–7. [Link]
(1):50–5. [Link] PMID: org/10.4103/0975-9476.140469. PMID: 25336844; PMCID: PMC4204283.
13638508. [38] Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Antidepressant activity of
[25] Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing standardized extract of Bacopa monniera in experimental models of depression in
generalized anxiety disorder: the GAD-7. Arch Intern Med 2006 May 22;166(10): rats. Phytomedicine 2002;9(3):207–11. [Link]
1092–7. [Link] PMID: 16717171. 00116. PMID: 12046860.
[26] Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck depression [39] Agarwa P, Sharma B, Fatima A, Jain SK. An update on Ayurvedic herb Convolvulus
inventory: twenty-five years of evaluation. Clin Psychol Rev 1988;(1):77–100. pluricaulis Choisy. Asian Pac J Trop Biomed 2014;4(3):245–52. [Link]
[27] Johns MW. A new method for measuring daytime sleepiness: the Epworth 10.1016/S2221-1691(14)60240-9. PMID: 25182446; PMCID: PMC3868798.
sleepiness scale. Sleep 1991;14(6):540–5. [Link] [40] Razack S, Kandikattu HK, Venuprasad MP, Amruta N, Khanum F, Chuttani K,
14.6.540. Mishra AK. Anxiolytic actions of Nardostachys jatamansi via GABA benzodiazepine
[28] Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh channel complex mechanism and its biodistribution studies. Metab Brain Dis 2018;
Sleep Quality Index: a new instrument for psychiatric practice and research. 33(5):1533–49. [Link] PMID: 29934858.
Psychiatr Res 1989;28(2):193–213. [Link] [41] Dhingra D, Goyal PK. Evidences for the involvement of monoaminergic and
90047-4. PMID: 2748771. GABAergic systems in antidepressant-like activity of tinospora cordifolia in mice.
Indian J Pharmaceut Sci 2008;70(6):761–7. [Link]
474X.49118. PMID: 21369437; PMCID: PMC3040870.