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Yes, adjunctive standardized Withania somnifera extract improved negative symptoms, general psychopathology, total PANSS symptoms, and perceived stress, but not positive symptoms, over 12 weeks. In 66 outpatients with schizophrenia or schizoaffective disorder experiencing a recent symptom exacerbation, the ashwagandha group had significantly greater reductions than placebo beginning at 4 weeks and continuing through study end. Reported effect sizes favored ashwagandha for PANSS negative symptoms (Cohen d = 0.83), PANSS general symptoms (d = 0.76), PANSS total symptoms (d = 0.83), and Perceived Stress Scale scores (d = 0.58), while improvement in PANSS positive symptoms did not reach statistical significance (d = 0.48).

The strongest signal was for negative symptoms, with additional benefit for general psychopathology and total symptom burden. Compared with placebo, adjunctive Withania somnifera extract significantly improved PANSS negative, general, and total scores, while positive symptoms were not significantly different between groups. In a post hoc subgroup with at least moderate baseline negative symptom severity, PANSS negative symptom change was 4.22 b1 2.86 with ashwagandha versus 0.25 b1 2.14 with placebo (t19 = 3.65, P = .002), with a large effect size of Cohen d = 1.61 (95% CI, 0.61 to 2.6).

Separation from placebo began at 4 weeks. Mixed-model repeated-measures analyses showed that improvements favoring standardized Withania somnifera extract over placebo in PANSS negative, general, and total symptoms, as well as perceived stress, first appeared at Visit 4, which corresponded to 4 weeks of treatment. These between-group differences were then sustained through the remainder of the 12-week trial.

Yes, perceived stress improved significantly more with adjunctive Withania somnifera extract than with placebo. Stress was measured with the Perceived Stress Scale, and the between-group effect size favored ashwagandha with Cohen d = 0.58. The improvement became significantly different from placebo by 4 weeks and remained so through week 12.

Yes, antipsychotic treatment escalation was less frequent in the ashwagandha group. During the 12-week study, 2 of 33 patients (6.1%) receiving standardized Withania somnifera extract had their antipsychotic dose increased, compared with 9 of 33 patients (27.3%) assigned to placebo, including 1 placebo-treated patient who had a second antipsychotic added (Fisher exact P = .044). The study reports this difference while also noting that positive symptom scores themselves were not significantly different between groups.

The study used standardized Withania somnifera extract titrated to 1,000 mg/day as an add-on to ongoing antipsychotic treatment. Participants started at 250 mg twice daily for the first week, then increased to 500 mg twice daily from week 2 onward, unless tolerability required a lower dose. Treatment lasted 12 weeks.

The trial enrolled adult outpatients aged 18 to 75 years with DSM-IV-TR schizophrenia or schizoaffective disorder who were in a recent symptom exacerbation despite antipsychotic treatment. Entry required a PANSS total score of at least 60 plus active positive symptom severity criteria, and the exacerbation had to have lasted at least 2 weeks but no more than 1 year. The efficacy sample included 66 patients, 33 assigned to standardized Withania somnifera extract and 33 to placebo.

Adverse events were described as mild to moderate and transient, with somnolence, loose stools or diarrhea, and epigastric discomfort reported more often with ashwagandha. In the Withania somnifera group, somnolence occurred in 21.1%, loose stool/diarrhea in 18.1%, epigastric discomfort/stomach pain in 9.1%, and dry mouth, hyperactivity, rash, and weight gain each in 6.1%. There were no statistically significant between-group differences for adverse events reported in at least 5% of either group.

No significant between-group safety differences were reported for body weight, vital signs, or laboratory measures. Over 12 weeks, mean weight gain was 2.4 lb in the standardized Withania somnifera group versus 1.72 lb with placebo, and systolic blood pressure, diastolic blood pressure, pulse, and temperature changes did not differ significantly between treatments. The article also states that laboratory measures and ECG findings were generally unremarkable and remained stable.

Inflammatory markers moved in a favorable direction with ashwagandha, but the differences were not statistically significant. High-sensitivity C-reactive protein declined by a mean of 1.08 (SD 6.98) mg/L in the Withania somnifera group and increased by 1.55 (SD 5.58) mg/L with placebo (P = .25). S100B declined by 12.98 (SD 112.89) pg/mL with ashwagandha and increased by 27.54 (SD 145.41) pg/mL with placebo (P = .72), and no correlations were found between biomarker changes and changes in PANSS scores.

No, this trial did not demonstrate a statistically significant biomarker mechanism for the clinical improvement. Although the rationale for standardized Withania somnifera extract was based on anti-inflammatory and immunomodulatory properties, hsCRP, S100B, and IL-6 did not differ significantly from placebo, and changes in these markers did not correlate with symptom change. The authors also noted that IL-2, IL-4, and IFN-b3 were detectable in only a minority of participants, which limited testing of the hypothesized Th1/Th2 rebalancing mechanism.

This was a 12-week randomized, double-blind, placebo-controlled adjunctive trial in outpatients already taking antipsychotic medication. Patients were assigned 1:1 to standardized Withania somnifera extract or matching placebo, and efficacy analyses included 66 patients who had at least one pre- and post-randomization PANSS assessment. The primary outcome was change from baseline to endpoint in PANSS total and PANSS positive, negative, and general symptom scores, with secondary outcomes including perceived stress, CGI improvement, inflammatory markers, medication changes, and safety measures.

The findings come from an early, relatively small 12-week study and need replication. The trial included 66 patients in the efficacy analysis, enrolled a specific population with recent symptom exacerbation rather than stable chronic illness, and had limited cytokine detectability, which prevented a full test of the proposed immune mechanism. The authors also note that longer studies could assess functional outcomes, cognitive benefits in more stable patients, and the optimal upper and lower dose range of standardized Withania somnifera extract.