Minocycline Add-on To Risperidone For Treatment Of Patients With Schizophrenia

Objective:It is difficult to improve negative symptoms and cognitive impairments in schizophrenia. Some previous pilot studies have shown that minocycline, a semi-synthetic second-generation tetracycline, is effective in treating for negative and/or cognitive symptoms in schizophrenia. The mechanism of minocycline treating for schizophrenia is still unknown and is speculated to be concerned with immune. The present study, a16-week randomized, double blind, placebo controlled trial, was designed to examine the efficacy and safety of minocycline for the treatment of negative symptoms, cognitive impairments and mechanism in patients with schizophrenia.Methods:(1) Subject:Ninety-two subjects who met DSM-IV study criteria whose course of the disease lesser than five years were recruited in the study. The patients were randomizedly divided into minocycline group (46cases,100mg per capsule, one capsule, twice a day) and placebo group (46cases, one capsule, twice a day). (2) Assessments of symptom:The efficacy was assessed by the change in negative symptoms assessed by the Scale for the Assessment of Negative Symptoms (SANS), the change in the Positive and Negative Syndrome Scale (PANSS), the change in the Scale for the Assessment of Positive Symptoms (SAPS), the change in the Clinical Global Impressions Severity Scale (CGI-S), and was assessed by the negative symptoms response rate, defined as the percentage of subjects with a50%or greater reduction in total SANS scores. The data were collected at baseline, at weeks4,8,12, and16, and at the end of treatment.(3) Assessments of cognition:Cognitive function were measured at baseline and at the end of study respectively. The cognitive test battery assessed eight cognition domains including11tests, eight of which from MATRICS Consensus Cognitive Battery (MCCB). The six cognition domains, attention/vigilance, working memory, reasoning and problem solving, speed of information processing, visual learning and memory, verbal learning and memory, were assessed by eight tests including the Continuous Performance Test-Identical Pairs (CPT-IP), Spatial Span, Mazes, Trail Making Test (TMT), Symbol Coding Test, Verbal Fluency, Brief Visuospatial Memory Test-Revised (BVMT-R), and Hopkins Verbal Learning Test-Revised (HVLT-R). In addition, theWisconsin Card Sorting Test (WCST-64), Grooved Pegboard Test (GPT) and Stroop Color-Word Task were used to further assess reasoning.(4) Assessment of immune factor:Immune factor were measured at baseline and at the end of study respectively. Serum TNF-α, DL-1β concentration were measured by quantitative enzyme-linked immunosorbent assay (elisa) using a commercially available kit (Bender MedSystems GmbH Campus Vienna Biocenter2A-1030Vienna, Austria, Europe), Serum S100B concentration were determined by elisa kit (Abnova). Serum NO concentration were measured by Nitric Oxide Detection Kit (nitrate reductase)(Nanjing jiancheng Bioengineering Institute). Each concentration was measured in duplicate.Seventy-nine (minocycline group:39cases; placebo group:40cases) patients completed the first visit. Among these, sixty-three patients (minocycline group:30cases; placebo group:33cases) completed the16-week trial. All data of seventy-nine patients were input SPSS19.0soft in order to make further stastical analysis.Results:(1) The effect of minocycline for treatment of negative symptoms in schizophrenia:Subjects receiving minocycline had greater improvements on SANS total scores (t=14.939P<0.001) and PANSS negative subscale scores (t=15.043P<0.001) when compared with those receiving the placebo. Rates of treatment response in the minocycline group (43.6%) were significantly higher than those in the placebo group (10.0%) after16weeks of treatment. (2) The effect of minocycline for treatment of cognitive symptoms in schizophrenia:There was no significant difference between the seven cognitive domains (P>0.05), except for the attention domain (t=0.672, P=0.044).(3) The effect of minocycline for treatment of immune factor in schizophrenia:There was no significant difference between the concentration of IL-1β, TNF-α, S100B (P>0.05). The decline of NO in minocycline group was more in placebo group(P<0.05).Conclusion:The addition of minocycline to atypical antipsychotic drugs in early schizophrenia had significant efficacy on negative symptoms but had a slight effect on the attention domains of patients with schizophrenia. Minocycline displayed simultaneously reduce the NO concentration in the schizophrenia, but it is to improve the negative symptoms by inhibiting the action to achieve the concentration of NO needs further studies to confirm.