Effectiveness of Ashwagandha in Schizophrenia Patients on Risperidone (WSE-SCZ)

The Effectiveness of Ashwagandha Extract as an Adjuvant Therapy in Reducing Interleukin-1β Levels and Positive and Negative Syndrome Scale (PANSS) Scores in Schizophrenia Patients Receiving Risperidone

This study aims to evaluate the effectiveness of Ashwagandha (Withania somnifera) extract as an adjuvant therapy in patients with schizophrenia who are receiving risperidone. Schizophrenia is a chronic mental disorder associated with neuroinflammation and immune dysregulation, including increased levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β).

In this study, patients diagnosed with schizophrenia are given standard treatment with risperidone, with or without additional Ashwagandha extract. The primary outcomes are changes in Interleukin-1β levels and clinical symptoms assessed using the Positive and Negative Syndrome Scale (PANSS).

The study aims to determine whether Ashwagandha extract supplementation can reduce inflammation and improve clinical symptoms in patients with schizophrenia. The findings support the use of Ashwagandha extract as a complementary therapy to enhance treatment outcomes in schizophrenia.

Study Overview

• Status: Completed
• Conditions: Neuroinflammation; Schizophrenia Patients
• Intervention / Treatment: Drug: Risperidone 4mg/day; Other: Placebo; Drug: Ashwagandha

Detailed Description

This randomized controlled trial was conducted at South Sulawesi Mental Hospital (RSKD Dadi), South Sulawesi Province, Makassar, Indonesia.

Schizophrenia is a chronic and severe psychiatric disorder characterized by disturbances in perception, cognition, emotion, and behavior. In addition to neurotransmitter imbalances, increasing evidence suggests that neuroinflammation and immune dysregulation play important roles in the pathophysiology of schizophrenia. Elevated levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), have been associated with disease severity and symptom progression.

Risperidone, an atypical antipsychotic, is commonly used as a first-line treatment for schizophrenia and is effective in reducing positive symptoms. However, many patients continue to experience residual symptoms, particularly negative and cognitive symptoms. Therefore, adjunctive therapies targeting alternative pathways, such as inflammation, are being explored to improve treatment outcomes.

Ashwagandha (Withania somnifera) is a traditional medicinal plant with known anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical and clinical studies suggest that Ashwagandha may modulate immune responses, reduce pro-inflammatory cytokines, and improve cognitive and behavioral functions. These properties make it a potential candidate as an adjunctive therapy in schizophrenia.

This study is designed to evaluate the effectiveness of Ashwagandha extract as an adjuvant to risperidone therapy in patients with schizophrenia. Participants diagnosed with schizophrenia are allocated to receive either standard treatment with risperidone alone or risperidone in combination with Ashwagandha extract. The primary outcomes of the study include changes in serum IL-1β levels and clinical symptom severity measured using the Positive and Negative Syndrome Scale (PANSS).

Data are collected at baseline and after the intervention period. Statistical analysis is conducted to compare changes in IL-1β levels and Positive and Negative Syndrome Scale (PANSS) scores between groups. The study aims to determine whether the addition of Ashwagandha extract provides additional benefits in reducing inflammation and improving clinical outcomes compared to standard therapy alone.

The results of this study are expected to contribute to the understanding of the role of immunomodulatory interventions in schizophrenia and to support the development of complementary therapeutic strategies for improving patient outcomes.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • South Sulawesi
    • Makassar, South Sulawesi, Indonesia, 90245
      • South Sulawesi Mental Hospital (RSKD Dadi)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male patients diagnosed with schizophrenia based on ICD-10/PPDGJ III criteria
• Aged 20-45 years
• Duration of illness ≤ 5 years
• Patients who have passed the acute phase (Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) < 15)
• Receiving risperidone 4 mg/day
• Willing to participate and provide written informed consent

Exclusion Criteria:

• Presence of organic comorbid diseases
• History of substance abuse (NAPZA) within the last 1 year, except caffeine and nicotine
• Use of anti-inflammatory drugs, antibiotics, or antioxidant agents
• Intellectual disability (mental retardation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Risperidone in combination with a placebo; Participants receive standard antipsychotic therapy with risperidone 4mg/day in combination with a placebo as a control condition for 8 weeks	Drug: Risperidone 4mg/day; Risperidone is administered as standard antipsychotic therapy according to clinical practice guidelines for the treatment of schizophrenia.; Other: Placebo; Placebo administered alongside risperidone, matched in appearance to the Ashwagandha preparation, used as a control condition.
Experimental: Risperidone in combination with Ashwagandha extract; Participants receive antipsychotic therapy with risperidone 4mg/day in combination with Ashwagandha (Withania somnifera) extract 1000mg/day as an adjuvant therapy for 8 weeks	Drug: Risperidone 4mg/day; Risperidone is administered as standard antipsychotic therapy according to clinical practice guidelines for the treatment of schizophrenia.; Drug: Ashwagandha; Standardized extract of Ashwagandha (Withania somnifera) 1000mg/day administered as an adjunctive therapy in combination with risperidone during the study period; Other Names: Withania somnifera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum Interleukin-1beta levels	The primary outcome is the change in serum Interleukin-1beta levels measured to evaluate the anti-inflammatory effect of the intervention	Baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Positive and Negative Syndrome Scale (PANSS) total score	Change in total Positive and Negative Syndrome Scale (PANSS) score from baseline to Week 8. The PANSS total score ranges from 30 to 210, with higher scores indicating more severe schizophrenia symptoms. A reduction in score indicates clinical improvement.	Baseline to week 8
Change in Positive and Negative Syndrome Scale subscale scores (positive, negative, general psychopathology)	Assessment of changes in Positive and Negative Syndrome Scale (PANSS) subscale scores from baseline to Week 8. The PANSS includes positive symptom, negative symptom, and general psychopathology subscales. Higher scores indicate more severe psychopathology, and reductions in scores indicate improvement.	Baseline to week 8
Correlation between change in serum Interleukin-1beta levels and change in Positive and Negative Syndrome Scale (PANSS) total score	Correlation between changes in serum Interleukin-1 beta levels and changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to Week 8 using correlation analysis (e.g., Pearson or Spearman correlation coefficient). The PANSS total score ranges from 30 to 210, with higher scores indicating more severe schizophrenia symptoms.	Baseline to week 8

Collaborators and Investigators

• Sponsor: Hasanuddin University
• Investigators: Principal Investigator: Masnaeni Awaliah, MD, Hasanuddin University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Actual): January 30, 2026
• Study Completion (Actual): January 31, 2026

Study Registration Dates

• First Submitted: May 2, 2026
• First Submitted That Met QC Criteria: May 2, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Schizophrenia; Interleukin-1beta; PANSS; Ashwagandha; Withania somnifera
• Additional Relevant MeSH Terms: Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroinflammatory Diseases; Schizophrenia; Inflammation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrimidinones; Risperidone; Ashwagandha
• Other Study ID Numbers: UH25040276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to privacy and confidentiality concerns, as well as institutional and ethical restrictions on data sharing. Only aggregated data will be reported in publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No