Abstract
Background
Metabolic syndrome (MetS) is a major side-effect of antipsychotic and antidepressant medications that increases risk for cardiac and neurological disorders and hinders long-term adherence to treatment. Integrated Yoga and Ayurveda (IYA) intervention can potentially aid in counteracting these side effects.
Objective
To evaluate the efficacy and safety of Integrated Yoga and Ayurveda (IYA) intervention in psychotropic associated metabolic syndrome (MetS) in patients with severe mental disorders
Materials and Methods
A single-arm exploratory observational trial was conducted in an outpatient setting at a major tertiary mental healthcare hospital in South India. The study included 29 consenting patients(11 females and 18 males) with severe mental disorders (SMDs) stable on anti-psychotic and antidepressant medications diagnosed with MetS (NCEP-ATP III criteria). A 45-day IYA intervention comprising an Ayurveda herbal formulation (Triphala choorna 6 gm per dose) with warm water twice daily and a 10-min specific yoga program was administered. Assessments were performed at the baseline and after 45 days for the following variables: anthropometry, blood pressure, lipid profile, fasting blood sugar, and safety profile consisting of Renal Function and Liver Function tests. Seventeen patients completed the study. Data on changes in anthropometry and biochemical markers was analyzed using paired samples t-test.
Results
A statistically significant reduction was observed in the following variables: body weight (p < 0.001), BMI (p < 0.001), Total cholesterol (p < 0.05), and triglycerides (p < 0.05). None of the patients reported any side effects of IYA. Clinical assessment at the end of 45 days did not reveal any worsening of psychotic symptoms.
Conclusion
IYA may serve as a safe and potentially effective adjuvant in addressing MetS in patients with SMDs who are on psychotropics.
Keywords: Integrated yoga and ayurveda, Metabolic syndrome, Triphala
1. Introduction
Psychotic disorders are associated with substantial mortality and morbidity. They affect individuals in the most productive years of their lives and are an important cause of social and financial burden [1]. Schizophrenia is a chronic and severe mental illness characterized by disorganized thoughts and behavior (positive symptoms), social withdrawal (negative symptoms), cognitive deficits, and socio-occupational dysfunction. It was ranked among the top 15 leading causes of disability worldwide in 2016 [2]. Depression is one of the most prevalent and debilitating psychiatric disorders and a major contributor to the global burden of diseases [3]. World Health Organization states that depression is the second-leading cause of disability in the world and is projected to rank first by 2030 [4]. It is also associated with high rates of suicidal behavior and mortality [5]. Bipolar disorder, also known as bipolar affective disorder, is marked by recurring episodes of mania or hypomania alternating with depression. It ranks among the top 10 leading causes of disability globally [6].
Antipsychotic medications are effective in managing psychotic symptoms and thereby improving the quality of life of patients. First-generation antipsychotics (FGAs) are effective against the positive symptoms of schizophrenia [7]. However, they may lead to a variety of extrapyramidal symptoms (EPS) (e.g., tremors, slurred speech, akathisia, and dystonia) [8]. Atypical or second-generation antipsychotics (SGAs) cause less EPS, but are significantly associated with reduced insulin sensitivity and metabolic syndrome (MetS) [9]. As a result of the reduction in activity due to the disorder itself as well as the adverse effects of the medications, the prevalence of metabolic syndrome is high in schizophrenia. A meta-analysis of 77 publications reported an overall rate of 32.5 % (95 % CI = 30.1 %–35 %) [10]. Weight gain, dyslipidemia, and impaired glucose metabolism are the major problems associated with metabolic syndrome in patients on SGA [9].
Antidepressant medications are the first-line treatment option for depression. Selective serotonin reuptake inhibitors (SSRIs) remain the gold-standard treatment for depression [11]. Nausea, fatigue, GI disturbances, sexual dysfunction, and weight gain are common side effects associated with antidepressant medications [12]. Commonly prescribed antidepressants are classified for their adverse cardiometabolic effects as high (Amitriptyline, Citalopram, Mirtazapine etc.) medium (escitalopram, sertraline, and fluoxetine) and low-risk [11]. Weight gain associated with Tricyclic Antidepressants (TCAs) is positively correlated with both dosage and duration of treatment, and is most pronounced with amitriptyline [13].
Mood stabilizers are the primary treatment for Bipolar Affective Disorder (BPAD) [6]. Weight gain appears to be the most prominent side effect of lithium and valproate. Valproate has been proven to be associated with weight gain in up to 50 % of its users [13].
As per the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria, MetS is defined by the presence of three or more of the following five criteria: increased waist circumference (males: ≥90 cm and for females: ≥80 cm), hypertriglyceridemia≥150 mg/dl (1.7 mmol/l), low HDL (males <40 mg/dl (1 mmol/l) and for females <50 mg/dl (1.3 mmol/l), elevated blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg or drug treatment for hypertension), and elevated blood sugar (fasting blood sugar ≥100 mg/dl (5.6 mmol/l) or drug treatment for diabetes mellitus) [14]. Among these, waist size was the most useful predictor of metabolic syndrome in antipsychotic-associated weight gain [10].
Both pharmacological and behavioral interventions have been said to be effective in treating psychotropics-induced weight gain [15]. Metformin has the most evidence for efficacy and is the most commonly used pharmacological agent in the management of psychotropic-induced weight gain, while topiramate, sibutramine, aripiprazole, and reboxetine have also been found to be reasonably effective [16]. However, a significant proportion of patients do not obtain benefit from conventional pharmacotherapy, and these medications also produce their own significant adverse effects, particularly topiramate and sibutramine [17]. Evidence suggests holistic lifestyle interventions like Ayurveda and Yoga may serve better in managing a multi-factorial lifestyle disorder such as MetS. A study incorporating Ayurveda and Yoga in the management of obesity reported that Ayurveda and Yoga showed promise as a low-cost alternative to traditional weight loss interventions with potential added benefits associated with sustainable holistic lifestyle modification and positive psychosocial changes. [18]. Plant-based formulations have been shown to reduce cardiovascular risk in obese adolescents by reducing inflammation, reducing weight and lipid profile, and regulating adipokines [19]. Triphala is a polyherbal compound that is commonly used in clinical practice. A systematic review of five RCTs demonstrated that adding Triphala to the dietary regimen of patients with obesity led to a statistically significant reduction in the body mass index and waist circumference compared to the controls [20]. A controlled trial with 12 months of follow-up reported that Triphala had a protective role in impaired glucose tolerance (IGT) and was useful as an adjuvant in managing T2DM [21]. Similarly, a systematic review of seven randomized controlled trials of yoga in patients with metabolic syndrome revealed evidence for beneficial effects in reducing waist circumference and systolic blood pressure [22].
Previously, in a pilot trial, we explored the effect of 5 months of adjuvant yoga therapy in managing anti-psychotic induced side effects in patients with chronic schizophrenia. We observed that yoga as an add-on helped reduce extra-pyramidal symptoms but did not significantly change the body mass index [23]. The current preliminary study aims to assess the safety and potential utility of an Integrated Yoga and Ayurveda (IYA) intervention on clinical signs and symptoms of MetS as an adjuvant to anti-psychotic medications through a single-arm prospective exploratory study.
2. Methodology
2.1. Study design
The study was conducted in the out-patient setting of the Department of Integrative Medicine, National Institute of Mental Health and Neurosciences, Bengaluru, from January to June 2022. The Human Ethics Committee for research in AYUSH and Integrative Medicine of NIMHANS approved the protocol in conformity with the Declaration of Helsinki. The trial was registered under CTRI as a prospective pre-post single arm observational study (Registration number: CTRI/2021/12/038515). All patients gave voluntary, written, informed consent before entering the study. Twenty-nine patients diagnosed with metabolic syndrome (NCEP-ATP III criteria) on stable dose of antipsychotic medications for the past 2 months were recruited.
2.2. Objectives
Primary objective.
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•
To evaluate the efficacy and safety of Integrated Yoga and Ayurveda (IYA) intervention in psychotropic associated metabolic syndrome (MetS) in patients with severe mental disorders
Secondary objective.
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•
To measure the changes in anthropometric and biochemical parameters in psychotropic associated metabolic syndrome (MetS) in patients with severe mental disorders
2.3. Sample size
There are no previous studies examining the effect of Ayurveda intervention in Antipsychotic induced metabolic syndrome. The sample size was estimated using the standard principles and methods [24]. As the study was a pilot study, considering a medium effect size of 0.5, a minimum of 30 patients were considered to detect a two-tailed difference of α – 0.05 with an estimated 90 % power.
2.4. Inclusion criteria
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1.
Patients with metabolic syndrome (as per NCEP-ATP III criteria).
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2.
Patients on psychotropic medication with BMI >24.9 and waist circumference ≥90 (male) ≥80 (female).
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3.
Patients on a stable dose of psychotropic medication for the past 8 weeks.
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4.
Patients in the age group of 18–45 years.
2.5. Exclusion criteria
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1.
Patients with persistent and uncontrolled thyroid dysfunctions.
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2.
Patients on medications for metabolic syndrome from alternative medical systems.
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3.
Patients with conditions where Kapalabhati are contraindicated, e.g., hypertension, seizure disorder, low back ache, glaucoma, recent abdominal surgery, hernia, etc.
2.6. Intervention
Intervention arm: Triphala churna [25] 6 g twice daily after food with warm water for 45 days was given to the patients. Triphala churna was procured from (Indian Medical Practitioners Co-operative Pharmacy and Stores Ltd (IMPCOPS), Chennai) a GMP-certified Ayurveda pharmacy. A 10-min yoga module for ameliorating metabolic syndrome was designed and taught by a trained yoga therapist to all individuals who had consented to the study. The video was shared with the patient, and they were advised to practice the yoga module twice daily for at least 5 days a week under the supervision of a family member. The yoga practice included two rounds of Kapalbhati with 30 strokes each (3 min), two rounds of Bhastrika with 20 strokes each (2 min), and 27 cycles of right nostril breathing (5 min). Compliance with the medicine and yoga practices was ensured through telephonic follow-ups every 2 weeks. Those with at least 80 % compliance were considered for the final analysis.
2.7. Assessments
The demographic and clinical information (history of presenting illness as well as any other medical illness, family & personal history, nutritional & lifestyle-related history) were collected with the help of a structured case record format. The safety of the IYA intervention was assessed by asking about any side effects to be reported by the patient or the caregiver that they attribute to the IYA intervention. Clinical assessments and the metabolic side effects associated with psychotropic usage were assessed at the baseline and post-intervention (after 45 days) by an independent psychiatrist. Anthropometric measurements such as weight, height, waist and hip circumference, and body mass index (BMI) were measured at baseline and after 45 days of treatment. Fasting blood sugar and Lipid profile were also assessed at baseline and the end of 45 days of treatment.
2.8. Statistical analysis
Statistical analysis was performed using the statistical package for social science software (SPSS 24.0) using the following tests. The outcome variables data was checked for normality using the Shapiro-Wilk test. The outcome variables Weight, BMI, Hip circumference, waist circumference, and total cholesterol (TC) were normally distributed, and they were analyzed with paired t-tests. Triglyceride data were not normally distributed and analyzed using the Wilcoxon signed Ranks test.
3. Results
A total of 53 patients were screened, out of which 35 patients met the inclusion criteria, and among them 29 consented to the study (Fig. 1). The sociodemographic details of the patients are provided in Table 1 Of the 29 patients, 23 patients were diagnosed with Schizophrenia/psychosis, two patients each had BPAD and Major depressive disorder, and one patient each was diagnosed with OCD and schizoaffective disorder. All patients reported weight gain after taking medication, dyslipidemia was observed in 17, diabetes in 5 patients and hypertension in 3 patients. 22 patients were not doing any type of vigorous physical activity as a part of their lifestyle whereas 7 patients reported physical activity 1–2 times in week (see Table 2).
Fig. 1.
CONSORT flow chart.
Table 1.
Demographic details of the patients.
| Gender | Age | Number | |
|---|---|---|---|
| Male Female |
18 11 |
20–30 31–40 41 and above 34.4 (±9.29) ∗∗ |
10 14 05 |
| Education | Employment status | ||
| Illiterate Below SSLC SSLC completed PU completed Graduates Post graduates |
5 2 4 3 11 4 |
Employed Unemployed Students |
21 4 4 |
| Socio economic status | Marital Status | ||
| Upper Middle Lower |
7 17 5 |
Married Unmarried |
18 11 |
∗∗ Mean age.
Table 2.
Details of treatment.
| Sl. No. | Class of Drugs | Pharmacological agent | N | Dose/day | n |
|---|---|---|---|---|---|
| 01 | Antipsychotics | Olanzapine | 09 | 2.5 mg | 01 |
| 7.5 mg | 02 | ||||
| 10 mg | 03 | ||||
| 20 mg | 03 | ||||
| Risperidone | 08 | 2 mg | 03 | ||
| 4 mg | 03 | ||||
| 6 mg | 02 | ||||
| Lurasidone | 02 | 40 mg | 02 | ||
| Clozapine | 02 | 100 mg | 01 | ||
| 450 mg | 01 | ||||
| Haloperidol | 02 | 2 mg | 02 | ||
| Quetiapine | 01 | 200 mg | 01 | ||
| Amisulpride | 01 | 600 mg | 01 | ||
| Ziprasidone | 01 | 40 mg | 01 | ||
| 02 | Antidepressants | Fluoxetine | 05 | 20 mg | 02 |
| 40 mg | 02 | ||||
| 60 mg | 01 | ||||
| Escitalopram | 03 | 20 mg | 03 | ||
| Sertraline | 01 | 300 mg | 01 | ||
| Desvenlafaxine | 01 | 50 mg | 01 | ||
| Clomipramine | 01 | 75 mg | 01 | ||
| 03 | Mood stabilizers | Lithium | 01 | 600 mg | 01 |
| Sodium valproate | 02 | 250 mg | 01 | ||
| 500 mg | 01 | ||||
| Lamotrigine | 01 | 100 mg | 01 | ||
| 04 | Benzodiazepines | Clonazepam | 01 | 1 mg | 01 |
3.1. Anthropometry and blood pressure
Of the 17 patients who completed the study, 13 had a significant reduction in weight and BMI. Ten patients obtained reduction in waist and hip circumference. Overall paired t-test (n = 17) revealed significant reductions in body weight and BMI. Though there was a change in waist/hip circumference, systolic and diastolic blood pressure as well, statistically the results were non-significant.
3.2. Lipid profile
Among the 17 patients, 8 had reduction in total cholesterol and triglycerides. Three patients showed reduction in Fasting Blood Sugar (FBS). Overall paired t-test (n = 17) revealed significant reductions in total cholesterol and triglycerides. Though there was a trend towards change in LDL, it was not significant statistically.
4. Discussion
Metabolic side effects are common in patients on psychotropic medications, particularly second-generation antipsychotics. [26]. Severe mental disorders require long term adherence to medication and metabolic syndrome is one among the major reasons for poor medication adherence which eventually results in relapse [27]. Addressing metabolic issues could potentially improve the adherence to psychotropic medication regime. Studies support the effectiveness of Ayurveda herbs and therapies and yoga practices in MetS. An effective management of the same can ensure drug adherence and thereby prevent relapse. There are studies in support of the effectiveness of Ayurveda polyherbal formulations and therapies and yoga practices in MetS. The pattern of diagnosis and class of drugs show a temporal relationship between the anti-psychotic medications and metabolic side effects. Srudies suggest the rate of metabolic syndrome in patients with schizophrenia were at least twice as high compared to others [28]. In the present study 83 % of the patients were diagnosed with schizophrenia/psychosis and 92 % of the patients were on second generation antipsychotics among them 41 % of the patients were on olanzapine. Weight gain, obesity, dyslipidemia and impaired glucose metabolism are the major metabolic side effects associated with second generation antipsychotic medications [9]. Studies suggest highest risk of metabolic liability of antipsychotics associated with Chlorpromazine, quetiapine, olanzapine and clozapine and moderate risk for risperidone. [29]. Hence in this study the efficacy of IYA on MetS was studied.
Triphala is a polyherbal formulation widely used in clinical practice. It is the combination of dried fruits of Phyllanthus emblica Linn., Terminalia chebula Retz., and Terminalia bellerica Roxb in equal quantities. Acording to Ayurveda it possesses Kapha dosha (Humour dominant with unctuousness), Medo dhatu (Adipose tissue) hara (pacifying) properties and is widely advised in the management of sthoulya (obesity) and prameha (disorders characterized by excessive urination including diabetes mellitus). Pathological state of Kapha dosha and Meda dhatu is the hallmark in metabolic disorders such as sthoulya and prameha. In the light of recent researches triphala is known for its antidiabetic, hypolipidemic and anti-obesogenic properties [30]. Controlled clinical studies with 12 months follow up suggest effectiveness of triphala in controlling impaired glucose tolerance (IGT) and effective in the treatment of T2DM [21]. An add-on triphala to atorvastatin 10 mg for three months has been reported to show significant (p < 0.0001) reduction in total cholesterol and cholesterol/HDL ratio compared to control [31].
In this study, reduction in FBS was seen in three patients and there was a significant decrease in weight and BMI, Total cholesterol and triglycerides (p < 0.05). Although some changes were observed in waist circumference, hip circumference, LDL, systolic blood and diastolic blood pressure as well, the results were not statistically significant. Table 3, Table 4, Table 5 Studies report that the average intervention duration of triphala in metabolic disorders ranges between 4 weeks and 6 months. In the current study triphala was given for a duration of 45 days. Administering triphala for longer duration may have brought a statistically significant change in waist circumference, hip circumference, LDL, systolic blood and diastolic blood pressure. In the current study palatability of the triphala was a major concern for drug compliance. The adverse events observed during the trial period were loose motion in 6 patients, nausea in 3 patients, vomiting in 2 patients, and gastritis and abdominal bloating in 1 subject respectively. Previous studies on triphala also report similar adverse events [20,32]. A retrospectively analyzing the koshta (Bowels), found that patients with krura koshta (Caustic bowels) had bloating and gastritis and mridu koshta (mild bowels) reported loose motions.
Table 3.
Changes in weight, BMI, hip circumference, waist circumference and lipid profile.
| Baseline (Mean ± SD) | After 45 days of intervention (Mean ± SD) | |
|---|---|---|
| Weight (Kg) | 90.75 ± 20.65 | 87.75 ± 20.33 |
| BMI (Kg/m2) | 32.51 ± 5.17 | 31.46 ± 5.29 |
| HC (cm) | 114.25 ± 8.84 | 113.95 ± 8.85 |
| WC (cm) | 108.44 ± 11.94 | 110.95 ± 8.38 |
| Total cholesterol (mg/dL) | 187.50 ± 16.09 | 179.63 ± 12.26 |
| Triglycerides (mg/dL) | 214.63 ± 50.10 | 192.63 ± 33.94 |
Table 4.
Showing the paired t-test results of weight, BMI, hip circumference, waist circumference and lipid profile.
| Paired Samples Test | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Paired differences | t | df | Sig. (2-Tailed) | Cohen's d effect size | ||||||
| Mean | Std. Deviation | Std. Error mean | 95 % Confidence interval of the difference | |||||||
| Lower | Upper | |||||||||
| Pair 1 | weight - weight-post | 2.0556 | 2.0428 | 0.4815 | 1.0397 | 3.0714 | 4.269 | 17 | 0.001 | 0.15 |
| Pair 2 | BMI - BMI-post | 0.7567 | 0.7165 | 0.1689 | 0.4004 | 1.1130 | 4.481 | 17 | 0.001 | 0.20 |
| Pair 3 | HC – HC-post | 0.2000 | 0.4435 | 0.1017 | −0.0137 | 0.4137 | 1.966 | 18 | 0.065 | 0.03 |
| Pair 4 Pair 5 |
TC - TC-post WC –WC post |
7.8750 0.24333 |
5.5146 0.56395 |
1.9497 0.13292 |
3.2647 −0.03711 |
12.4853 0.52378 |
4.039 1.831 |
7 17 |
0.005 0.085 |
0.51 0.24 |
Table 5.
Showing the Wilcoxon signed Ranks test results of triglycerides.
| Ranks | ||||
|---|---|---|---|---|
| N | Mean Rank | Sum of Ranks | ||
| Triglycerides - post - triglycerides | Negative ranks | 8d | 4.50 | 36.00 |
| Positive ranks | 0e | 0.00 | 0.00 | |
| Ties | 0f | |||
| Total | 8 | |||
| d. Triglycerides - post < triglycerides | ||||
| e. Triglycerides - post > triglycerides | ||||
| f. Triglycerides - post = triglycerides | ||||
| Triglycerides post - triglycerides | ||||
| Z | −2.521b | |||
| Asymp sig (two tailed) | 0.012 | |||
a. Wilcoxon Signed Ranks Test.
b. Based on positive ranks.
A meta-analysis by Mizuno et al., on pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia reported that concomitant metformin showed a mean difference of −3.17 kg (95 % CI: −4.44 to −1.90 kg) compared to placebo. It significantly decreased fasting blood glucose and lipid levels [33]. The main mechanism of weight loss may be by reduction of insulin resistance and suppression of appetite [34]. A meta-analysis of four randomized, double-blinded, placebo-controlled trials indicates that topiramate was effective for managing antipsychotic-related weight gain, showing a mean weight loss difference of 3.95 kg (95 % CI, 1.77 to 16.12) compared to placebo, although the results were highly heterogeneous (I2 = 86 %) [35]. It promotes weight loss by stimulating lipoprotein lipase, inhibiting carbonic anhydrase and lipogenesis, suppressing appetite, and increasing satiety [36]. In this study, we found that triphala was effective in countering weight gain and dyslipidemia associated with psychotropic use. The results were comparable with conventional management strategies though the study had a small sample size and a shorter duration of intervention. A major advantage of triphala was the absence of any significant adverse effects, worsening of psychiatric symptoms, and improvement in energy level, appetite and bowel clearance reported by the patients.
The scope of yoga in metabolic syndrome is well explored and yoga-based interventions have been found effective in addressing the associated physical and psychological components. [[37], [38]]. A validated yoga module for obesity, DM, and dyslipidemia for Indian population has been trialed, which includes sithilikarana vyayama (relaxation practices), asana (postures), pranayama (breathing practices), suryanamaskara and dhyana (meditation) [[39], [40], [41]]. Considering the low motivation among patients with severe mental disorders, practicability, feasibility and to ensure daily practice, this study used a tailor-made module comprising of fast breathing practices and right nostril breathing for a duration of 10 min. The practices were easy to learn and repeat which did not required any additional training. Studies also report an average duration of yoga intervention ranging from 8-12 weeks in management of metabolic disorders. [22]
5. Strengths and limitations of the study
5.1. Strengths
The recruitment of stable psychiatric patients on regular medication and the use of standardized assessments for metabolic syndrome represent significant methodological strengths of this study. The implementation of a standardized Integrative Yoga Ayurveda (IYA) protocol with Triphala as the key intervention ensures treatment fidelity and reproducibility for future research.
5.2. Limitations
Several limitations warrant consideration when interpreting our findings. The small sample size (n = 30) restricts the generalizability of the results, while the high dropout rate (33 %) impacts the completeness of data. Palatability issues with Triphala emerged as the primary reason for discontinuation, highlighting an important challenge for clinical applications of this intervention.
While our results showed statistically significant reductions in body weight and BMI (P < 0.05), we acknowledge that statistical significance does not necessarily equate to clinical significance. In our study, the mean reduction in BMI was 0.75 kg/m2 over the 45-day intervention period. This magnitude of BMI reduction, while statistically significant, falls below the threshold typically considered clinically meaningful for metabolic syndrome management. Current clinical guidelines suggest that a reduction of at least 1–2 kg/m2 in BMI or 5–7 %of initial body weight is necessary to achieve substantial improvements in metabolic parameters (Magkos et al., 2016[42]). It's important to consider that the modest duration of our intervention (45 days) likely limited the magnitude of BMI reduction achieved. Longer interventions of 3-6 months typically demonstrate more substantial and clinically meaningful weight reductions. Additionally, psychiatric patients on psychotropic medications face unique challenges in weight management due to medication-induced metabolic alterations, making even modest improvements potentially valuable in this specific population (Correll et al., 2015[43]). The primary aim of this pilot study was to assess feasibility and preliminary efficacy rather than definitive clinical outcomes. While the observed BMI reduction (0.75 kg/m2) may have limited immediate clinical impact, it suggests a positive trajectory that could potentially achieve clinical significance with longer intervention duration or modified formulation approaches to improve adherence.
An inherent selection bias may exist among those who completed the full protocol, as these participants potentially would have had stronger pre-existing beliefs in Ayurvedic approaches or higher baseline motivation levels. This form of attrition bias could have influenced our reported outcomes.
The absence of a control group further limits our ability to attribute the observed changes specifically to the IYA intervention rather than to other factors such as regression to the mean, natural fluctuations in metabolic parameters, or non-specific therapeutic effects. Future research should address these limitations through larger sample sizes, control group designs, improved formulation palatability, and pre-specified assessments of both statistical and clinical significance.
Additionally, we acknowledge that lifestyle behaviors such as nutrition and exercise patterns can significantly influence metabolic parameters and could potentially confound intervention outcomes. To address this concern, participants were explicitly instructed to maintain their pre-study dietary habits and physical activity levels throughout the intervention period, with no additional dietary or lifestyle modifications advised beyond the Triphala intervention itself.
Nevertheless, we recognize that unintentional behavioral changes may have occurred simply through study participation (the Hawthorne effect), potentially influencing our results. This limitation has been acknowledged in our revised limitations section, and we recommend that future studies incorporate monitoring of dietary intake and physical activity using validated instruments to better control for these potential confounding variables.
6. Learning and future recommendations
Triphala in the form of a capsule or tablet would help to minimize the palatability issues and improve the drug compliance. Increasing the duration of intervention from 45 days to 8–12 weeks could improve the outcomes. Add-on shodhana (bio purificatory) procedures like Virechana (medically induced purgation) and later adding triphala for a specific duration can produce better sustained effects on metabolic parameters. Moreover, understanding the synergistic effects of Triphala's components could significantly enhance therapeutic applications for metabolic syndrome. Network pharmacology studies, such as that conducted by Dongre and Majumdar (2024)[44] on Chandraprabha Vati for metabolic syndrome, offer valuable methodological frameworks for future research on Triphala. While existing network pharmacology studies have primarily focused on Triphala's anticancer properties, applying similar approaches to investigate its effects on metabolic parameters could elucidate crucial multi-target mechanisms of action. Such studies would help identify key bioactive compounds and their molecular targets within metabolic pathways, potentially revealing how Triphala's constituents work synergistically to address the complex pathophysiology of metabolic syndrome. A yoga module can also be added with practices of mild to moderate intensity physical activities without exceeding a total duration of 15 min. Future research integrating both network pharmacology findings and clinical interventions could provide deeper insights into optimizing Triphala formulations for metabolic syndrome management.
7. Conclusions
Metabolic syndrome (MetS) is a major side-effect of psychotropic medications that hinders long-term adherence to treatment. This study evaluated the efficacy of an integrated yoga and ayurveda intervention (IYA) on MetS in patients on psychotropic medications and found promise in reducing metabolic parameters without exacerbation of psychiatric symptoms and disturbing the pharmacological action of psychotropic medications. Hence, IYA may serve as a safe and potentially effective adjuvant in addressing MetS in patients with SMDs.
Author contributions
Santhosh Chandrasenan (SC): Data curation, Writing-original draft. Umesh Chikkanna (UC) & Kishore Kumar Ramakrishna (KKR): Conceptualization, Methodology, Data curation, Writing-review & editing, Supervision. Hemant Bhargav (HB) & Nishitha Jasti (NJ): Conceptualization, Methodology, Data curation, Writing-original draft, Supervision. Shivarama Varambally (SSV): Conceptualization, Methodology, Data curation, Writing-review & editing, Visualization, Supervision. Amritha Meena Suresh (AMS): Conceptualization, Writing-review & editing, Supervision.
Declaration of generative AI in scientific writing
During the preparation of this work, the author(s) have not used any generative AI and AI-assisted technologies in the writing process of the manuscript.
Funding sources
None. No incentives were given to the participants to increase compliance/adherence.
Acknowledgements
This work was supported by the Centre for Excellence in Research (CoE) grant titled “Yoga and Ayurveda in Neuroscience: Translational Research Accelerator program (YANTRA)” [grant number 3988] under the Ayurswasthya Yojana of Ministry of AYUSH, Government of India.
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