Effectiveness and tolerability of warm-supplementing kidney yang added to risperidone in improving cognitive impairment in patients with schizophrenia: An 8-week, multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Certain herbal medicines have been reported to be effective in the treatment of psychiatric conditions, and combination treatment with drugs and herbal medicines has been reported to be useful in enhancing treatment efficacy and reducing recovery time and adverse events (AEs).

OBJECTIVE: The purpose of this study was to investigate the effectiveness and tolerability of warm-supplementing kidney yang (WSKY) added to risperidone in improving cognitive impairment and negative symptoms (ie, cognitive function) in patients with schizophrenia.

METHODS: This 8-week, multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in patients who met the clinical classification for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were recruited from 3 centers (including inpatient and outpatient clinics) and were evenly randomized to receive WSKY or placebo added to risperidone for 8 weeks. Primary assessments were conducted at weeks 2, 4, and 8. A clinical response was defined as a ≥50% reduction score (from baseline) on the Positive and Negative Syndrome Scale (PANSS), a ≥30% reduction score (from baseline) on the Scale for the Assessment of Negative Symptoms (SANS), or a ≥50% reduction score (from baseline) on the Hamilton Rating Scale for Depression (HAM-D-17). Cognitive function was assessed using the Wisconsin Card Sorting Test (WCST) at baseline and end point. Extrapyramidal AEs were assessed weekly using the Abnormal Involuntary Movement Scale (AIMS) and the Rating Scale for Extrapyramidal Side Effects (RSESE). AEs were assessed by patient interviews conducted at each clinic visit and also by the Treatment Emergent Symptoms Scale (TESS) scores.

RESULTS: One-hundred twenty patients (62 males, 58 females; mean [SD] age, 34.4 [9.4] years; range, 18-45 years; baseline mean [SD] PANSS score, 88.7 [12.3]) were included in this study. Risperidone- and WSKY-treated patients had statistically significant improvements at end point in the number of completed categories (P = 0.019), perseverative responses (P = 0.041), perseverative errors (P = 0.040), and total errors (P = 0.049) on the WCST compared with placebo. The improvements in the PANSS, SANS, and HAM-D-17 scores were not significantly different between the 2 groups at week 8 for observed case and last-observation-carried-forward (LOCF) analyses. The response rates (LOCF) for the PANSS scores in the WSKY and placebo groups were 55.0% and 35.0%, respectively (P = 0.028), while the SANS scores were 63.3% and 45.0% (P = 0.044) and the HAM-D-17 were 35.0% and 45.0% (P = 0.264). There were no significant between-group differences in scores on the AIMS, RSESE, or TESS.

CONCLUSIONS: The results of this study suggest that WSKY added to risperidone significantly improved cognitive function in these patients, as measured by the number of completed categories, perseverative responses, perseverative errors, and total errors on the WCST compared with placebo. The response rates in the WSKY group for the PANSS and SANS scores were significantly higher compared with placebo. All treatments were generally well tolerated.