Efficacy and safety of loxapine for inhalation in the treatment of agitation in
patients with schizophrenia: a randomized, double-blind, placebo-controlled
trial.
Author(s): Allen MH, Feifel D, Lesem MD, Zimbroff DL, Ross R, Munzar P, Spyker DA, Cassella
JV.
Affiliation(s): University of Colorado Depression Center, Aurora, CO 80045, USA.
michael.allen@ucdenver.edu
Publication date & source: 2011, J Clin Psychiatry. , 72(10):1313-21
OBJECTIVE: The objective of this study was to assess the efficacy and safety of
inhaled loxapine in the treatment of agitation in patients with psychotic
disorders.
METHOD: In this randomized, double-blind, placebo-controlled study, 129 agitated
patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) were
randomized to receive in a clinical or hospital setting a single inhalation of 5
or 10 mg of loxapine or placebo administered using the Staccato loxapine for
inhalation device. The inhalation device delivered thermally generated drug
aerosol to the deep lung for rapid absorption. The primary efficacy measure was
change on the Positive and Negative Syndrome Scale-excited component (PANSS-EC) 2
hours following treatment. Secondary outcomes included the Clinical Global
Impressions-Improvement scale (CGI-I), Behavioral Activity Rating Scale (BARS),
and time to first rescue medication. The study was conducted between September
2006 and January 2007.
RESULTS: Differences were statistically significant (P < .05) between placebo and
both 5-mg and 10-mg doses on the CGI-I and the CGI-I responder analyses at 2
hours and in time to first rescue medication, and they were statistically
significant (P < .05) between placebo and 10-mg loxapine on the PANSS-EC 20
minutes after administration continuing through 2 hours and in change from
baseline BARS. Three serious adverse events occurred at least 6 days after
treatment, but none were judged related to study treatment. The most common
adverse events were sedation and dysgeusia (22% and 17%, respectively, in the
10-mg group, and 14% and 9%, respectively, in the placebo group).
CONCLUSIONS: Inhaled loxapine was generally safe and well tolerated and produced
rapid improvement in agitated patients with psychotic disorders. Statistically
significant differences in efficacy were found for the 10-mg dose compared with
placebo, with results suggesting 5 mg may be effective. The delivery of loxapine
by inhalation may provide a rapid, well-tolerated option for treating acute
psychotic agitation that allows patients to avoid the aversive effects and loss
of autonomy often associated with use of intramuscular medications. Further
investigation of this new loxapine formulation is warranted.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00369577.
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