Examining the safety, efficacy, and patient acceptability of inhaled loxapine for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults

References

• Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26(1):42–49. doi:10.1016/j.genhosppsych.2003.08.00214757302
   PubMed Web of Science ®Google Scholar
• Garriga M, Pacchiarotti I, Kasper S, et al. Assessment and management of agitation in psychiatry: expert consensus. World J Biol Psychiatry. 2016;17(2):86–128. doi:10.3109/15622975.2015.113200726912127
   PubMed Web of Science ®Google Scholar
• Citrome L. Addressing the need for rapid treatment of agitation in schizophrenia and bipolar disorder: focus on inhaled loxapine as an alternative to injectable agents. Ther Clin Risk Manag. 2013;9:235–245. doi:10.2147/TCRM.S3148423723707
   PubMed Web of Science ®Google Scholar
• Citrome L, Volavka J. Violent patients in the emergency setting. Psychiatr Clin North Am. 1999;22(4):789–801.10623971
   PubMed Web of Science ®Google Scholar
• Martinez-Raga J, Amore M, Di Sciascio G, et al. 1st international experts’ meeting on agitation: conclusions regarding the current and ideal management paradigm of agitation. Front Psychiatry. 2018;9:54. doi:10.3389/fpsyt.2018.0005429535649
   PubMed Web of Science ®Google Scholar
• Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012;13(1):26–34. doi:10.5811/westjem.2011.9.686622461918
   PubMedGoogle Scholar
• Zimbroff DL, Marcus RN, Manos G, et al. Management of acute agitation in patients with bipolar disorder: efficacy and safety of intramuscular aripiprazole. J Clin Psychopharmacol. 2007;27(2):171–176. doi:10.1097/JCP.0b13e318033bd5e17414241
   PubMed Web of Science ®Google Scholar
• Zeller SL, Citrome L. Managing agitation associated with schizophrenia and bipolar disorder in the emergency setting. West J Emerg Med. 2016;17(2):165–172. doi:10.5811/westjem.2015.12.2876326973742
   PubMedGoogle Scholar
• Citrome L. Handbook of Treatment-resistant Schizophrenia. London, UK: Springer Healthcare; 2013.
   Google Scholar
• 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(1):61–68. doi:10.1111/acps.1226224606117
   PubMed Web of Science ®Google Scholar
• Ng AT, Zeller SL, Rhoades RW. Clinical challenges in the pharmacologic management of agitation. Prim Psychiatry. 2010;17(8):46–52.
   Google Scholar
• Currier GW, Medori R. Orally versus intramuscularly administered antipsychotic drugs in psychiatric emergencies. J Psychiatr Pract. 2006;12(1):30–40.16432443
   PubMedGoogle Scholar
• 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(3):318–325. doi:10.1111/j.1742-1241.2011.02890.x22226343
   PubMed Web of Science ®Google Scholar
• Popovic D, Nuss P, Vieta E. Revisiting loxapine: a systematic review. Ann Gen Psychiatry. 2015;14:15–015-0053–3. eCollection 2015. doi:10.1186/s12991-015-0053-3
   Web of Science ®Google Scholar
• Allen MH, Feifel D, Lesem MD, et al. Efficacy and safety of loxapine for inhalation in the treatment of agitation in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011;72(10):1313–1321. doi:10.4088/JCP.10m06011yel21294997
   PubMed Web of Science ®Google Scholar
• Lesem MD, Tran-Johnson TK, Riesenberg RA, et al. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011;198(1):51–58. doi:10.1192/bjp.bp.110.08151321200077
   PubMed Web of Science ®Google Scholar
• Kwentus J, Riesenberg RA, Marandi M, 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(1):31–40. doi:10.1111/j.1399-5618.2011.00975.x22329470
   PubMed Web of Science ®Google Scholar
• Noymer P, Myers D, Glazer M, et al. The Staccato system: inhaler design characteristics for rapid treatment of CNS disorders. Resp Drug Deliv. 2010;1:11–20.
   Google Scholar
• Citrome L. Aerosolised antipsychotic assuages agitation: inhaled loxapine for agitation associated with schizophrenia or bipolar disorder. Int J Clin Pract. 2011;65(3):330–340. doi:10.1111/j.1742-1241.2010.02615.x21199198
   PubMed Web of Science ®Google Scholar
• Spyker DA, Munzar P, Cassella JV. Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers. J Clin Pharmacol. 2010;50(2):169–179. doi:10.1177/009127000934786619915181
   PubMed Web of Science ®Google Scholar
• Spyker DA, Voloshko P, Heyman ER, Cassella JV. Loxapine delivered as a thermally generated aerosol does not prolong QTc in a thorough QT/QTc study in healthy subjects. J Clin Pharmacol. 2014;54(6):665–674. doi:10.1002/jcph.25724375070
   PubMed Web of Science ®Google Scholar
• Dinh KV, Myers DJ, Noymer PD, Cassella JV. In vitro aerosol deposition in the oropharyngeal region for Staccato loxapine. J Aerosol Med Pulm Drug Deliv. 2010;23(4):253–260. doi:10.1089/jamp.2009.081420528148
   PubMed Web of Science ®Google Scholar
• Currier G, Walsh P. Safety and efficacy review of inhaled loxapine for treatment of agitation. Clin Schizophr Relat Psychoses. 2013;7(1):25–32. doi:10.3371/CSRP.CUWA.03251323538290
   PubMedGoogle Scholar
• Kapur S, Zipursky R, Remington G, Jones C, McKay G, Houle S. PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophrenia. Am J Psychiatry. 1997;154(11):1525–1529. doi:10.1176/ajp.154.11.15259356559
   PubMed Web of Science ®Google Scholar
• Seeman P. Targeting the dopamine D2 receptor in schizophrenia. Expert Opin Ther Targets. 2006;10(4):515–531. doi:10.1517/14728222.10.4.51516848689
   PubMed Web of Science ®Google Scholar
• Singh AN, Barlas C, Singh S, Franks P, Mishra RK. A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes. J Psychiatry Neurosci. 1996;21(1):29–35.8580115
   PubMed Web of Science ®Google Scholar
• Javitt DC, Duncan L, Balla A, Sershen H. Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action. Mol Psychiatry. 2005;10(3):275–287. doi:10.1038/sj.mp.400155215278098
   PubMed Web of Science ®Google Scholar
• Galen US, Inc. Adasuve (Loxapine Inhalation Powder) Package Insert. Souderton, PA, USA: Galen US, Inc.; 2017.
   Google Scholar
• Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY. D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology (Berl). 1995;120(3):365–368.8524985
   PubMed Web of Science ®Google Scholar
• Chakrabarti A, Bagnall A, Chue P, et al. Loxapine for schizophrenia. Cochrane Database Syst Rev. 2007;4:CD001943. doi:10.1002/14651858.CD001943.pub2
   Web of Science ®Google Scholar
• de Berardis D, Fornaro M, Orsolini L, et al. The role of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders: a clinical review. Int J Mol Sci. 2017;18(2). doi:10.3390/ijms18020349
   Web of Science ®Google Scholar
• Meltzer HY, Matsubara S, Lee JC. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390–392.2576319
   PubMedGoogle Scholar
• Stockmeier CA, DiCarlo JJ, Zhang Y, Thompson P, Meltzer HY. Characterization of typical and atypical antipsychotic drugs based on in vivo occupancy of serotonin2 and dopamine2 receptors. J Pharmacol Exp Ther. 1993;266(3):1374–1384.8103793
   PubMed Web of Science ®Google Scholar
• Midha KK, Hubbard JW, McKay G, Hawes EM, Hsia D. The role of metabolites in a bioequivalence study 1: loxapine, 7-hydroxyloxapine and 8-hydroxyloxapine. Int J Clin Pharmacol Ther Toxicol. 1993;31(4):177–183.8500919
   PubMed Web of Science ®Google Scholar
• Wong YC, Zuo Z. Brain disposition and catalepsy after intranasal delivery of loxapine: role of metabolism in PK/PD of intranasal CNS drugs. Pharm Res. 2013;30(9):2368–2384. doi:10.1007/s11095-013-1080-x23739987
   PubMed Web of Science ®Google Scholar
• Zeller S, Zun L, Cassella JV, Spyker DA, Yeung PP. Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses. BJ Psych Open. 2017;3(6):285–290. doi:10.1192/bjpo.bp.117.005363
   Google Scholar
• Citrome L. Comparison of intramuscular ziprasidone, olanzapine, or aripiprazole for agitation: a quantitative review of efficacy and safety. J Clin Psychiatry. 2007;68(12):1876–1885.18162018
   PubMed Web of Science ®Google Scholar
• San L, Estrada G, Oudovenko N, et al. 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. Eur Neuropsychopharmacol. 2018;28(6):710–718. doi:10.1016/j.euroneuro.2018.03.01029724638
   PubMed Web of Science ®Google Scholar
• McDowell M, Nitti K, Kulstad E, et al. Clinical outcomes in patients taking inhaled loxapine, haloperidol, or ziprasidone in the emergency department. Clin Neuropharmacol. 2019. doi:10.1097/WNF.0000000000000325
   Web of Science ®Google Scholar
• Cassella JV, Spyker DA, Yeung PP. A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers. Int J Clin Pharmacol Ther. 2015;53:963–971. doi:10.5414/CP20245726501204
   PubMed Web of Science ®Google Scholar
• Gross N, Greos LS, Meltzer EO, et al. Safety and tolerability of inhaled loxapine in subjects with asthma and chronic obstructive pulmonary disease–two randomized controlled trials. J Aerosol Med Pulm Drug Deliv. 2014;27(6):478–487. doi:10.1089/jamp.2013.111424745666
   PubMed Web of Science ®Google Scholar
• Roberts J, Gracia Canales A, Blanthorn-Hazell S, Craciun Boldeanu A, Judge D. Characterizing the experience of agitation in patients with bipolar disorder and schizophrenia. BMC Psychiatry. 2018;18(1): 104-018-1673-3. doi:10.1186/s12888-018-1673-3
   Web of Science ®Google Scholar
• Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2: 12–7525-2–12. doi:10.1186/1477-7525-2-12
   Google Scholar
• Jorgensen TR, Emborg C, Dahlen K, Bogelund M, Carlborg A. The effect of the medicine administration route on health-related quality of life: results from a time trade-off survey in patients with bipolar disorder or schizophrenia in 2 Nordic countries. BMC Psychiatry. 2016;16: 244-016-0930-6. doi:10.1186/s12888-016-0930-6
   Web of Science ®Google Scholar
• Kahl KG, Negt P, Wollmer A, Jung S, Kruger TH. Inhaled loxapine for acute treatment of agitation in patients with borderline personality disorder: a case series. J Clin Psychopharmacol. 2015;35(6):741–743. doi:10.1097/JCP.000000000000040226448403
   PubMed Web of Science ®Google Scholar
• Roncero C, Ros-Cucurull E, Grau-Lopez L, Fadeuilhe C, Casas M. Effectiveness of Inhaled Loxapine in dual-diagnosis patients: a case series. Clin Neuropharmacol. 2016;39(4):206–209. doi:10.1097/WNF.000000000000015327015036
   PubMed Web of Science ®Google Scholar
• Sztrymf B, Chevrel G, Bertrand F, et al. Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation. Crit Care. 2010;14(3):R86. doi:10.1186/cc901520459867
   PubMed Web of Science ®Google Scholar
• Jaffe R, Siniscalchi M, Cruz-Luna N, Cosgrove D. Inhaled loxapine for ECT pretreatment for agitation. J Ect. 2016;32(2):146. doi:10.1097/YCT.000000000000027626439438
   PubMed Web of Science ®Google Scholar
• Selim S, Riesenberg R, Cassella J, et al. Pharmacokinetics and safety of single-dose inhaled loxapine in children and adolescents. J Clin Pharmacol. 2017;57(10):1244–1257. doi:10.1002/jcph.93228510296
   PubMed Web of Science ®Google Scholar