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.