Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia

Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.

Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of ultra-resistant schizophrenia. The subjects are the patients with ultra-resistant schizophrenia who have responded poorly to clozapine treatment. They keep their original clozapine treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. The efficacies of NMDAE plus AIFA and NMDAE plus placebo will be compared.

Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE) for both primary and secondary outcomes . All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

• Change of Positive and Negative Syndrome Scale (PANSS) [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of scale for the Assessment of Negative Symptoms (SANS) total score [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Chang of positive subscale of PANSS [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of negative subscale of PANSS [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of general Psychopathology subscale of PANSS [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of clinical Global Impression [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of global Assessment of Functioning [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of hamilton Rating Scale for Depression [Срок оценки: week 0, 2, 4, 6, 9, 12]
• Change of quality of Life Scale [Срок оценки: week 0, 2, 4, 6, 9, 12]