Ditan Qingnao Formula for treating negative symptoms of schizophrenia with marrow-deficiency and phlegm-obscuring pattern: a randomized double-blind controlled trial

To evaluate the clinical efficacy and safety of Ditan Qingnao Formula in treating negative symptoms of schizophrenia with marrow-deficiency and phlegm-obscuring pattern, and to explore its mechanism.

A randomized, double-blind, placebo-controlled trial was conducted at Beijing Huilongguan Hospital from September 20, 2023, to July 30, 2024. A total of 134 patients with schizophrenia with predominant negative symptoms were randomly allocated (1:1) to either the Ditan Qingnao Formula or placebo groups using dynamic block randomization. The Ditan Qingnao Formula group received Ditan Qingnao Formula granules, whereas the placebo group received traditional Chinese medicine (TCM) placebo granules, each sachet containing 7 g of granules. One sachet was administered orally twice daily (morning and evening) for a 6-week intervention period. The primary outcome measure was the Marder Negative Symptom Scale (MNSS) score, and secondary outcome measures included the Positive and Negative Symptome Scale (PANSS, including total, Negative Symptom Subscale, Positive Symptome Subscale and General Psychopathology Subscale), TCM syndrome, and Personal and Social Performance Scale (PSPS) scores. Vital signs and hematological indicators were also collected for safety analysis and mechanism research. Modified intention-to-treat (131 cases) and per-protocol set (121 cases) analyses were employed. All statistical analyses were performed using RStudio software.

After 6 weeks of treatment, the MNSS score in the Ditan Qingnao Formula group was lower than that in the placebo group with superior improvements in PANSS total, Negative Symptom Subscale, General Psychopathology Subscale, TCM syndrome, and PSPS scores (all P<0.05). No serious adverse events were reported, and the overall incidence of adverse events was low during the trial. At week 4, the Ditan Qingnao Formula group exhibited significant reductions in MNSS (β = -0.099, t = -4.05, P < 0.01), PANSS total (β = -0.076, t = -4.07, P < 0.01), and TCM syndrome scores (β = -0.102, t = -2.17, P<0.05), indicating an improvement in negative symptoms. By week 6, the PSPS score had increased markedly (β = 0.081, t = 3.33, P < 0.01). After 6 weeks of treatment, compared with baseline, the Ditan Qingnao Formula group showed a significant decrease in pro-inflammatory cytokines interleukin (IL)-1β and IL-17 (both P<0.05) and a concurrent increase in anti-inflammatory cytokines IL-4 and IL-10 (both P<0.05). IL-1β level was significantly lower in the Ditan Qingnao Formula group than in the placebo group (P<0.05).

Ditan Qingnao Formula improves negative symptoms and social functioning in schizophrenia with favorable safety, potentially through neuroinflammatory modulation mechanisms.