PLACID study: A randomized trial comparing the efficacy and safety of inhaled loxapine versus intramuscular aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder.

The aim of the study was to investigate the efficacy and safety of inhaled loxapine compared with the intramuscular (IM) antipsychotic aripiprazole in acutely agitated patients with schizophrenia or bipolar I disorder. PLACID was an assessor-blind, parallel-group trial conducted in 23 centres in the Czech Republic, Germany, Spain, and Russia. Patients (aged 18-65 years) diagnosed with schizophrenia or bipolar I disorder experiencing acute agitation (Clinical Global Impression [CGI]-Severity score ≥ 4) while hospitalized or attending an emergency room were randomized to receive up to two doses of inhaled loxapine 9.1 mg or IM aripiprazole 9.75 mg (≥ 2 h between doses) during the 24-h study period. The primary efficacy endpoint was time to response (CGI-Improvement score 1 [very much improved] or 2 [much improved]). The primary analysis included randomized patients who provided informed consent (full analysis set [FAS]); the safety analysis included all patients who received study medication. The FAS comprised 357 patients (enrolled December 2, 2014 - October 31, 2016). The between-treatment difference in median time to CGI-Improvement response was 10 min (95% CI 0.0-30.0); p = 0.0005) in favour of inhaled loxapine (median [95% CI]: 50 min [30.0-50.0] vs 60 min [50.0-90.0] with IM aripiprazole); the difference was significant at 10 min (responders: 14% [loxapine] vs 4% [aripiprazole]; p = 0.001). There were no safety issues. Inhaled loxapine reduced agitation faster than IM aripiprazole, supporting its use as a first-line option for managing acute agitation in patients with schizophrenia or bipolar disorder.

Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis.

Dysbindin-1 is a relatively ubiquitous protein in the brain which is involved in the modulation of synaptic homeostasis. The dysbindin-1 gene (DTNBP1) has been associated with schizophrenia and bipolar disorder diagnoses. However, its contribution to the severity of the clinical and neurocognitive expression of these disorders remains controversial. We aimed to explore the association between DTNBP1 and the phenotypes which are more directly linked with the underlying biology, such as age at onset and neurocognitive impairment. The present family sample comprised 894 Caucasian individuals: 268 patients affected by functional psychosis [58% with illness onset before 18 years, mean age at onset (SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single nucleotide polymorphisms were genotyped in all individuals and their transmission disequilibrium was tested in relation to: (i) the risk for psychosis; (ii) patients' age at onset; and (iii) familial neurocognitive performance (including IQ estimation and executive functioning). In early-onset families a 5-marker haplotype encompassing exons 2-4 and the surrounding introns was significantly over-transmitted to cases, while in adult-onset families two haplotypes corresponding to the region between introns 4 and 7 were over-transmitted to cases. Estimated IQ was associated with the rs760666 marker in the whole sample, whereas a significant association between executive functioning and the rs2619522 marker appeared in early-onset families. Our findings confirm the role of the dysbindin-1 gene in the risk for functional psychosis and show a differential haplotypic risk pattern in families with early as opposed to adult onset in the affected offspring.