Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study.

BACKGROUND: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. METHODS: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. CONCLUSIONS: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability.

Validation of the Russian Version of the Positive and Negative Syndrome Scale (PANSS-Ru) and Normative Data.

Objective: The Positive and Negative Syndrome Scale (PANSS) is widely used to assess psychopathology. The Russian version (PANSSRu) has not been validated, and normative data for the Russian-speaking population currently do not exist. The aims of this study were to 1) complete linguistic validation for the PANSSRu, 2) perform psychometric validation of the Russian translation, and 3) present norms for the Russian and Belarusian population. Design: Validation and norms of the PANSS-Ru occurred in three stages-Stage I: linguistic validation; Stage II: psychometric validation of the translated version for 40 inpatients with schizophrenia and other psychoses; and Stage III: norms for 533 census-matched inpatients, outpatients, and healthy control subjects. Results: The rating criteria (PANSS-Ru), interview guide (SCI-PANSSRu), informant questionnaire (IQ-PANSS-Ru), and scoring form (PANSS QuikScore-Ru) were linguistically and psychometrically validated. Convergent validity between the PANSS subscale scores and total score with the Clinical Global Impressions-Severity Scale (CGI-S) were moderate (r=0.41-0.60) to high (r=0.61-0.80). Cronbach's α (0.88) verified internal consistency, and intra-class correlation coefficient (ICC) comparisons had a range of 0.83. Percentile normative data collected from 533 subjects are presented. Conclusion: This is the largest population-based study providing linguistic and psychometric validation of the PANSS-Ru. Normative data can provide clinicians with a benchmark of psychopathology and inform the efficacy of treatment interventions.

Identification of 5-hydroxytryptamine receptor gene polymorphisms modulating hyperprolactinaemia in antipsychotic drug-treated patients with schizophrenia.

OBJECTIVES: Hyperprolactinaemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 subtype receptors in the pituitary gland. Although dopamine is considered the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by the secretagogues thyrotrophin releasing hormone, vasoactive intestinal polypeptide and serotonin (5-hydroxytryptamine; 5-HT). METHODS: We describe the association between HPRL and a set of 29 SNPs from 5-HT receptor genes HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6 in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) who were treated with classical and/or atypical antipsychotic drugs. RESULTS: None of the studied autosomal markers were found to be associated with HPRL. However, a significant association was established between various HTR2C polymorphisms and HPRL. CONCLUSIONS: This study revealed an association between HPRL and X-chromosome haplotypes comprised of the rs569959 and rs17326429 polymorphisms.