Treatment Response and GWAS Risk Allele rs2514218 (C) of the Dopamine D2 Receptor Gene in Inpatients with Schizophrenia.

INTRODUCTION: The pathophysiological mechanisms of acute schizophrenia are largely unknown, but it is widely accepted that dopamine D2 receptors (DRD2s) are involved in psychosis treatments for schizophrenic patients. We suggest that genetic variation in these receptors may play a role in patients' responses to commonly used antipsychotics, particularly D2-blockers. METHODS: This study included adult patients with ICD-10 diagnoses of schizophrenia and current acute psychosis who were treated with antipsychotics. All patients underwent genotyping for DRD2 rs2514218 polymorphism. The definition of overall treatment response was based on changes in treatment scheme: no changes indicated a good response, and changes indicated a limited response. RESULTS: There were 275 inpatients (38.1% of whom were female; mean age = 32.7 years, SD = 11.1 years) who met the inclusion criteria. Of the participants, 99 were good responders (34% of whom were female), and 176 were limited responders (40% of whom were female). No differences in demographic, premorbid, or disease characteristics were found. The number of patients that were homozygous for the risk allele was significantly greater in the limited response group than in the good response group. CONCLUSION: Our findings suggest that the risk variant at the DRD2 locus can be used as an indicator for patients' responses to antipsychotics without direct DRD2-blocking, thereby shortening the time needed for drug selection.

Safety and efficacy of aviandr in patients with generalized anxiety disorder: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, pilot study.

Generalized anxiety disorder (GAD) is associated with an imbalance in the functioning of the stimulating neurotransmitter systems in human's brain. We studied the safety and therapeutic efficacy of aviandr, the new noradrenergic and specific serotonergic antidepressant, for GAD patients in the phase II, double-blind, placebo-controlled, randomized, multicenter, pilot trial at 17 clinical sites of the Russian Federation. 129 eligible patients were 18 years and older and met the criteria for GAD diagnosis. The patients were randomly assigned (1:1:1) to receive oral aviandr at daily dose of 40 mg (cohort 1, n = 41) or 60 mg (cohort 2, n = 43) or placebo (cohort 3, n = 43) for 8 weeks. The patients were assessed by the Hamilton anxiety scale (HAM-A), Hamilton Depression Scale (HAM-D), Clinical Global Impression Scale (CGI-S), Visual Analogue Scale and vital signs. At week 8, the decreases of the HAM-A score were achieved in 53∙7%, 47∙7% and 16∙3% in cohorts 1, 2 and 3, respectively. Changes of HAM-A, HAM-D, CGI-S, and CGI-I scores in aviandr-treated patients were superior to placebo (p < 0∙001). The psychic components of anxiety decreased on the first day, throughout the 8 weeks of treatment and on a follow-up week after aviandr discontinuation. Aviandr (40 mg daily dose) reduced drowsiness compared to baseline, was safe, well-tolerated and did not cause serious or severe adverse events or signs of withdrawal syndrome within one week after treatment completion. Aviandr at both 40 and 60 mg daily doses demonstrated therapeutic efficacy in GAD patients over placebo.

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.