Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses
Scott Zeller, Leslie Zun, James V Cassella, Daniel A Spyker, Paul P Yeung, Scott Zeller, Leslie Zun, James V Cassella, Daniel A Spyker, Paul P Yeung
Abstract
Background: Efficacy of inhaled loxapine 5 or 10 mg in treating agitation was shown using the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) in two Phase III randomised, double-blind, placebo-controlled trials in 344 agitated patients with schizophrenia and 314 patients with bipolar I disorder (Clinicaltrials.gov: NCT00628589, NCT00721955).
Aims: To examine the five individual items comprising the PANSS-EC and the percentage of patients achieving a clinical response (reduction of ≥40%) in PANSS-EC (Response-40) for these two studies.
Method: Response-40 was examined at the primary end-point (2 h) and over time.
Results: Response-40 and each PANSS-EC item score were statistically significant v. placebo at 2 h and at each assessment time point for both doses.
Conclusions: Inhaled loxapine produced rapid improvement in agitated patients with schizophrenia or bipolar I disorder, achieving Response-40 at the first assessment (10 min post dose). These results highlight the effectiveness of loxapine across all components of agitation as measured by the PANSS-EC.
Declaration of interest: S.Z. is a member of the speakers bureau for Grupo Ferrer. L.Z. has been a speaker and grant recipient for Teva Pharmaceuticals. J.V.C. and D.A.S. were employees of Alexza Pharmaceuticals during execution of the studies, and are currently paid consultants for and have received stock and/or stock options from Alexza Pharmaceuticals. P.P.Y. is a full-time employee and receives stock options from Teva Pharmaceuticals.
Copyright and usage: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
Figures
References
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). APA, 2013.
- Alderfer BS, Allen MH. Treatment of agitation in bipolar disorder across the life cycle. J Clin Psychiatry 2003; 64 (suppl 4): 3–9.
- Hankin CS, Bronstone A, Koran LM. Agitation in the inpatient psychiatric setting: a review of clinical presentation, burden, and treatment. J Psychiatr Pract 2011; 17: 170–85.
- Marder SR. A review of agitation in mental illness: treatment guidelines and current therapies. J Clin Psychiatry 2006; 67 (suppl 10): 13–21.
- Nordstrom K, Allen MH. Alternative delivery systems for agents to treat acute agitation: progress to date. Drugs 2013; 73: 1783–92.
- Bourdinaud V, Pochard F. Survey of management methods for patients in a state of agitation at admission and emergency departments in France [in French]. Encephale 2003; 29: 89–98.
- Adasuve [prescribing information]. Alexza Pharmaceuticals, 2013.
- European Medicines Agency. Adasuve (loxapine) Inhalation Powder: EU Summary of Product Characteristics. ().
- Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, et al. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry 2011; 198: 51–8.
- Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, et al. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord 2012; 14: 31–40.
- Citrome L. Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. Int J Clin Pract 2012; 66: 318–25.
- Montoya A, Valladares A, Lizan L, San L, Escobar R, Paz S. Validation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) in a naturalistic sample of 278 patients with acute psychosis and agitation in a psychiatric emergency room. Health Qual Life Outcomes 2011; 9: 18.
- Emsley R, Rabinowitz J, Torreman M. The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophr Res 2003; 61: 47–57.
- Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res 2005; 79: 231–8.
- Pratts M, Citrome L, Grant W, Leso L, Opler LA. A single-dose, randomized, double-blind, placebo-controlled trial of sublingual asenapine for acute agitation. Acta Psychiatr Scand 2014; 130: 61–8.
- Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry 2007; 68: 1876–85.
- Cassella J, Fishman R, Spyker D. Inhaled loxapine rapidly improves acute agitation in schizophrenic patients. Presented at: American Psychiatric Association 162nd Annual Meeting, 16–21 May 2009, San Francisco, California, USA Available at: .
- Spyker DA, Munzar P, Cassella JV. Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers. J Clin Pharmacol 2010; 50: 169–79.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). APA, 2000.
- Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76.
- Kay SR. Significance of the positive-negative distinction in schizophrenia. Schizophr Bull 1990; 16: 635–52.
- Dinh K, Myers DJ, Noymer PD, Cassella JV. In vitro aerosol characterisation of Staccato® Loxapine. Int J Pharm 2011; 403: 101–8.
Source: PubMed