How to Use Adjunctive Ashwagandha in Schizophrenia Exacerbation
How can clinicians add standardized Withania somnifera extract to antipsychotic treatment for outpatients with schizophrenia or schizoaffective disorder during a recent symptom exacerbation?
Some outpatients with schizophrenia or schizoaffective disorder continue to have negative symptoms, general psychopathology, and stress despite ongoing antipsychotic treatment during an active exacerbation. This study provides a specific add-on regimen and patient selection approach for standardized Withania somnifera extract in that setting.
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Confirm that the patient matches the studied population
Use this approach only for adult outpatients aged 18 to 75 years with DSM-IV-TR schizophrenia or schizoaffective disorder. The study required PANSS total score of at least 60 plus active positive symptom severity, defined as a score of at least 5 on any 1 positive symptom item or at least 4 on any 2 items of the positive symptom cluster or unusual thought content. The symptom exacerbation had to have lasted at least 2 weeks but no more than 1 year, and patients had to be receiving antipsychotic medication for at least 4 weeks.
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Exclude patients with the study's main contraindications
Do not apply this regimen to patients with a positive pregnancy test, pregnancy, breastfeeding, unstable medical disorders, known allergy to standardized Withania somnifera extract, or a clinical situation requiring imminent psychiatric hospitalization. The trial also excluded patients receiving antibiotics, antiviral or antiparasitic medications, immunosuppressive therapy, daily NSAIDs, or aspirin doses above 81 mg/day. Positive tests for illicit drugs were exclusionary, although marijuana and alcohol use were allowed case by case in the study.
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Continue antipsychotic treatment as the foundation
Add the extract to ongoing antipsychotic therapy rather than using it instead of antipsychotic medication. In the trial, psychiatrists were permitted to increase the antipsychotic dose or add a second antipsychotic if clinically needed during the exacerbation, but switching to another antipsychotic led to study discontinuation. Mood stabilizer and antidepressant dose changes, and addition of sedative-hypnotics, were also allowed.
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Start the standardized extract and titrate to the target dose
Use a standardized extract of Withania somnifera given as 250 mg twice daily for the first week, for a total of 500 mg/day. At week 2, titrate to 500 mg twice daily, for a target dose of 1,000 mg/day, and maintain that dose for the remainder of the 12-week treatment period unless tolerability requires a lower dose. The study used identical capsules and a standardized product to improve consistency.
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Monitor adherence and reassess symptoms across the 12 weeks
The study used pill counts and pill reconciliation at each visit to assess adherence. Including screening, there were 6 visits over 12 weeks, with PANSS and Perceived Stress Scale assessments performed at every visit. Track negative symptoms, general psychopathology, total symptom burden, and perceived stress specifically, because those were the domains in which benefit was demonstrated.
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Set response expectations around the 4-week mark
Do not expect immediate separation from placebo. In this trial, significant between-group improvement favoring standardized Withania somnifera extract began at 4 weeks and continued through week 12 for PANSS negative, general, and total symptoms and for perceived stress. Positive symptoms improved numerically more with the extract but were not significantly different from placebo.
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Watch for the adverse effects seen more often in the trial
Monitor for mild to moderate transient somnolence, loose stool or diarrhea, and epigastric discomfort or stomach pain, which were more common with standardized Withania somnifera extract. Somnolence occurred in 21.1%, loose stool or diarrhea in 18.1%, and epigastric discomfort or stomach pain in 9.1% of the active-treatment group. Weight, vital signs, laboratory measures, and ECG findings were generally stable and not significantly different from placebo over 12 weeks.
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Do not use inflammatory biomarkers to judge clinical response
The study measured hsCRP, S100B, and cytokines, but these changes were not significantly different from placebo and did not correlate with symptom improvement. hsCRP and S100B declined numerically in the active-treatment group, yet between-group differences were not significant. Based on this trial, routine clinical response assessment should rely on symptom and stress measures rather than biomarker change.
Clinical Considerations
- This was an early 12-week study with 66 patients in the efficacy analysis, so the findings require replication.
- The evidence applies best to outpatients with recent symptom exacerbation rather than to chronically stable patients with persistent symptoms.
- Benefit was shown for negative symptoms, general psychopathology, total symptoms, and perceived stress, but not for positive symptoms.
- The study did not establish the optimal upper and lower dose range for standardized Withania somnifera extract.
Bottom Line
For outpatients with schizophrenia or schizoaffective disorder in a recent exacerbation despite antipsychotic treatment, adjunctive standardized Withania somnifera extract titrated to 1,000 mg/day over 12 weeks improved negative symptoms, general psychopathology, total symptoms, and stress, with benefit emerging by 4 weeks.
