Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

UNLABELLED: The serotoninergic system as a target for add-on treatment seems to be a promising approach in patients with schizophrenia. OBJECTIVE: To clarify if selective 5HT-6 antagonist AVN-211 (CD-008-0173) adds clinical and cognitive effects to stable antipsychotic treatment. METHODS: A randomized, double-blind, placebo-controlled, add-on, 4r-week trial in 47 schizophrenia patients (21 patients receiving study drug and 26 receiving placebo) who were stabilized on antipsychotic medication was performed. Seventeen patients from the study drug group and 25 patients from the placebo group completed the trial. Treatment effects were measured using clinical rating scales and attention tests. RESULTS: With no differences at baseline, there was a significant difference between the groups in Positive and Negative Syndrome Scale (PANSS) positive subscale score (p = 0.058) in favor of patients in the treatment group at the endpoint. The PANSS positive subscore (p = 0.0068) and Clinical Global Impression-Severity (CGI-S) (p = 0.048) score significantly changed only in the treatment group. Only in the placebo group were significant changes in Calgary Depression Rating Scale (CDRS) total score registered. The indices of attention tests at endpoint did not show differences between the groups, with the exception of the scope of change in the results of the subtest VIII of the Wechsler Adult Intelligence Scale (WAIS), which showed difference between the groups (p = 0.02) and was significantly larger in the treatment group. Only inside the study drug group, significant changes in selectivity and continuous attention were observed regarding total correct responses (p = 0.0038) and reaction time (p = 0.058) in the Continuous Attention Task (CAT) test. CONCLUSION: Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.

Double-blind placebo-controlled randomized efficacy and safety trial of add-on treatment of dimebon plus risperidone in schizophrenic patients during transition from acute psychotic episode to remission.

BACKGROUND: There is evidence that blockade of 5-HT 6 receptors can improve cognitive dysfunction in schizophrenic patients. A number of antagonists of 5-HT6 receptors are in development as cognitive enhancers. One of the agents with relatively strong 5-HT6 activity is dimebon. We tested the hypothesis that this 5-HT6 antagonist administered in the early stage of stabilization after an acute episode can improve both neurocognitive and clinical symptoms in schizophrenia. A phase II study of dimebon as add-on to risperidone therapy was conducted. SUBJECTS AND METHODS: 56 male subjects with paranoid schizophrenia were included in the study. All the patients demonstrated therapeutic response to risperidone as treatment of the acute psychotic episode. After 4 weeks of stability patients were randomized into two groups with placebo or dimebon add-on treatment in a 1 to 1 ratio for 8 weeks. PANSS, CGI-S, CSDS and NSA-16 were used as clinical measures of symptom severity. Different aspects of memory, psycho-motor coordination and executive functioning were assessed with a battery of cognitive tests. Clinical and cognitive assessment was performed twice: after a patient was randomized and 2 months later. RESULTS: Severity of negative symptoms (by NSA-16) were significantly lower in the dimebon group then in the placebo group (p=0.036). Patients in the dimebon group demonstrated improvement in more cognitive dimensions than patients in the placebo group, including working memory, attention, psycho-motor coordination and planning. CONCLUSION: Dimebon as add-on therapy to antipsychotic treatment in the period of stabilization after an acute episode can improve some aspects of clinical and cognitive status in schizophrenic patients.