Clinical Summary
Clinical Summary: Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study
Patients with schizophrenia or schizoaffective disorder often remain burdened by negative symptoms, general psychopathology, and stress during symptom exacerbations despite ongoing antipsychotic treatment. This trial tests whether adding standardized Withania somnifera extract can improve those harder-to-treat symptom domains without adding major tolerability problems.
Design
a random-assignment, double-blind, placebo-controlled study
N
Sixty-six randomized patients (n = 33 per group) provided efficacy data.
Population
Male or female outpatients aged 18 to 75 years, of any race, with DSM-IV-TR schizophrenia or schizoaffective disorder
Duration
12 weeks
Key Findings
- Beginning at 4 weeks and continuing to the end of treatment, WSE produced significantly greater reductions in PANSS negative, general, and total symptoms compared to placebo, with Cohen d: 0.83, 0.76, 0.83, respectively.
- PSS scores improved significantly with WSE treatment compared to placebo, with Cohen d: 0.58, and time to significant separation favoring WSE began at Visit 4 (ie, at 4 weeks of treatment) and was sustained throughout the remainder of the 12-week study.
- WSE-treated subjects were significantly more likely to achieve ≥ 20% improvements in PANSS negative, general, and total symptom scores, with the NNT ranging from 3 for negative symptoms to 4 for general and total symptoms.
- Antipsychotic treatment escalation was less frequent with WSE: 2 (6.1%) WSE-treated subjects had their antipsychotic drug dosage increased versus 9 (27.3%) placebo-assigned subjects who either had their antipsychotic drug dosage increased (n = 8) or had a second antipsychotic drug added (n = 1) (Fisher exact P = .044).
- In the post hoc subgroup with moderate severity PANSS negative symptom scores, mean ± SD change in PANSS negative symptom subscores was 4.22 ± 2.86 with WSE versus 0.25 ± 2.14 with placebo (t19 = 3.65, P = .002), with Cohen d = 1.61, 95% CI = 0.61 to 2.6.
Clinical Bottom Line
Adjunctive standardized Withania somnifera extract at 1,000 mg/d improved negative symptoms, general psychopathology, total symptoms, and stress over 12 weeks in outpatients with schizophrenia or schizoaffective disorder experiencing a recent exacerbation. The benefit emerged by 4 weeks and was accompanied by minimal safety concerns in this trial.
Practice Implications
- Consider adjunctive standardized Withania somnifera for patients with schizophrenia or schizoaffective disorder who have ongoing negative symptoms, general psychopathology, and stress despite antipsychotic treatment during a recent exacerbation.
- Set expectations that benefit was not immediate: significant separation from placebo began at 4 weeks and continued through 12 weeks.
- Monitor for mild to moderate transient adverse events that were more common with WSE, especially somnolence (21.1%), loose stool/diarrhea (18.1%), and epigastric discomfort/stomach pain (9.1%).
- Do not use biomarker change to judge response in routine practice based on this study, because hsCRP, S100B, and IL-6 changes were not significantly different between treatments.
