Objective: To describe the efficacy and safety of inhaled loxapine, a new formulation of an older antipsychotic being developed for the treatment of agitation associated with schizophrenia or bipolar disorder.
Data Sources: A literature search was conducted by querying http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search terms ‘loxapine’ AND ‘agitation’, ‘inhaled loxapine’, ‘staccato loxapine’. The manufacturer was asked to provide copies of posters presented at national and international meetings, and to provide any copies of papers currently in press.
Study Selection: All available reports of studies were identified.
Data Extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports.
Data Synthesis: Inhaled loxapine is delivered using a handheld device that produces a thermally generated condensation aerosol free of excipients or propellants. Time to maximum plasma concentration is approximately 2 min. In two phase III studies (one in subjects with schizophrenia, the other in subjects with bipolar disorder) inhaled loxapine 5 and 10 mg were both superior to placebo as early as 10 min after administration, as measured using the Positive and Negative Syndrome Scale excited component. Pooling together data from three efficacy studies, NNT for response for inhaled loxapine 5 or 10 mg vs. placebo were 4 (95% CI 3–5) and 3 (95% CI 3–4), respectively, with response defined as achieving a Clinical Global Impressions – Improvement score of 1 or 2 at 2 h postdose. This effect size is in the range observed for intramuscular administration of other antipsychotics for agitation associated with schizophrenia or bipolar disorder. There were no clinically relevant signals for the emergence of extra-pyramidal side effects or akathisia. The most commonly encountered adverse event appears to be dysgeusia (distorted taste sense or bad taste), with a NNH vs. placebo of 10 (95% CI 7–22) or 12 (95% CI 8–26), for loxapine 10 or 5 mg, respectively.
Conclusions: Inhaled loxapine appears efficacious and tolerable for the treatment of agitation associated with schizophrenia or bipolar disorder. Although simple to self-administer, inhaled loxapine requires a degree of cooperation from the recipient and thus will not be a substitute for an injection during psychiatric emergencies when the patient is actively refusing medication treatment. The efficacy and safety of inhaled loxapine in elderly patients and in outpatient care settings remain to be established.