Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated patients outside the hospital setting: protocol for a phase IV, single-arm, open-label trial

IntroductionThere is a need for fast-acting, non-injection antiagitation treatments that are well tolerated and can be used outside of healthcare facilities. In phase II/III trials, an inhaled formulation of loxapine (ADASUVE®), a well-established, first-generation antipsychotic agent, provided rapid control of mild to moderate agitation in the hospital setting. The present study was designed to investigate the safety and efficacy of inhaled loxapine when self-administered outside the hospital setting.Methods and analysisThis phase IV, multicentre, single-arm, open-label clinical trial is being conducted in five countries in Europe: Spain, Germany, Norway, Romania and Austria. The aim is to include approximately 500 patients with schizophrenia or bipolar disorder who previously received and responded well to inhaled loxapine in the hospital setting. Eligible patients will be followed up for 6 months from baseline. They will be given a 10 mg dose of inhaled loxapine to self-administer outside the hospital setting to treat an agitation episode, should one occur. Patients will also be given a short-acting beta-agonist bronchodilator for treatment of possible severe respiratory side effects. The primary endpoint is incidence of serious adverse events (AEs) and respiratory AEs of special interest related to use of inhaled loxapine outside the hospital setting. Secondary endpoints include incidence of other AEs, Clinical Global Impression-Improvement scores up to 2 hours after self-administration of inhaled loxapine, time to improvement of agitation, patient satisfaction with treatment, treatment outcomes according to agitation severity and concordance between the patient (or a family member/caregiver) and the physician in scoring of agitation severity and the decision to self-administer inhaled loxapine.Ethics and disseminationThe protocol received ethics committee approval in the participating countries between January and August 2016. The results of this study will be disseminated through one or more scientific papers.Trial registration numberEudraCT2015-003331-36;NCT02525991; Pre-results.

Inhaled Loxapine for The Treatment of agitation in Borderline Personality Disorder

Introductioninhaled loxapine has shown efficiency in the treatment of the mild-moderate agitation syndrome of schyzophrenia and mania patients. Its rapid response and calming effect non-sedative allow to hypothesize reasonable efficiency and tolerability in borderline personality disorder diagnosed patients.aimsanalyze the efficiency and tolerability of inhaled loxapine as a pharmacological approach in the treatment of agitation in borderline personality disorder (BPD) clinical diagnosed patients.Materials and methodan application was administered for every agitation episode in BPD patients treated with inhaled loxapine in the emergency room or the psychiatric ward, which included B aRS and CGI-S scales for the evaluation of each episode and its severity, before and after its use. Other secondary measures of efficiency were taken into account, such as requirement of physical restrain.Resultsin the majority of evaluated episodes inhaled loxapine decreased notably initial B aRS and CGI-S values and no serious clinical side effects attributable to this medication were observed.Conclusionin our sample, inhaled loxapine was efficiency and well tolerated pharmacological intervention for agitation in BPD patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Treatment of acute psychotic agitation: gaps in the evidence base

SummaryTreatment of psychotic agitation is an area that is very poorly evidenced, principally because research evidence from patients with moderate agitation may not generalise to the more severely agitated patients. There is a significant gap between current treatment recommendations and what is seen in clinical practice. There are also big differences in clinical practice between different units treating seemingly similar patient groups. This commentary considers possible reasons for these findings and also discusses non-pharmacological interventions, which probably contribute more to the management of psychotic agitation than does the choice of one antipsychotic drug over another.

Respiratory differences associated with culture aeration in Azotobacter vinelandii

Respiratory oxygen uptake of nitrogen-fixing Azotobacter vinelandii cells was altered by culturing at different levels of culture agitation (aeration). Cells were grown at low agitation or moderate agitation and with three different carbon substrates. The low-agitation cultures had much lower dissolved-oxygen concentrations than moderate-agitation cultures at the stage of growth at which they were studied. The respiration systems of cells from the moderate-agitation cultures had lower apparent affinities (higher Ks (O2) values) for oxygen than cells grown at low agitation. The higher Ks (O2)) values were dependent on the presence of Ca2+ and (or) Mg2+ in the medium. In low-agitation cultures, the oxygen concentrations were below the Ks (O2 values and the respiration rates in the cultures were therefore well below the maximal respiration (Vmax) rates. The oxygen concentrations in moderate-agitation cultures were above the Ks (O2) values and the culture respiration rates were much higher. The culture oxygen concentration relative to the Ks (O2) had a much greater effect on culture respiration rate than did the Vmax. It is proposed that changes in the respiration system resulting from culture agitation (aeration) reflect an "oxygen-sensing mechanism" that regulates respiration. This would provide at least a partial explanation for the increased respiration rates with increased culture oxygen concentration in A. vinelandii.Key words: Azotobacter, oxygen, respiration, nitrogen fixation.