Effectiveness of Ashwagandha in Schizophrenia Patients on Risperidone

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.

• Risperidone 4mg/day (Drug): Risperidone is administered as standard antipsychotic therapy according to clinical practice guidelines for the treatment of schizophrenia.
• Ashwagandha (Drug), also known as Withania somnifera: Standardized extract of Ashwagandha (Withania somnifera) 1000mg/day administered as an adjunctive therapy in combination with risperidone during the study period
• Placebo (Other): Placebo administered alongside risperidone, matched in appearance to the Ashwagandha preparation, used as a control condition.

Primary outcomes

• Change in serum Interleukin-1beta levels [Baseline to week 8]: The primary outcome is the change in serum Interleukin-1beta levels measured to evaluate the anti-inflammatory effect of the intervention

Secondary outcomes

• Change in Positive and Negative Syndrome Scale (PANSS) total score [Baseline to week 8]: 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.
• Change in Positive and Negative Syndrome Scale subscale scores (positive, negative, general psychopathology) [Baseline to week 8]: 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.
• Correlation between change in serum Interleukin-1beta levels and change in Positive and Negative Syndrome Scale (PANSS) total score [Baseline to week 8]: 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.

Sex: Male, ages: 20 Years to 45 Years

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)

• Masnaeni Awaliah, MD, Principal investigator, Hasanuddin University