Agitation (excessive motor or verbal activity) can be associated with
schizophrenia or bipolar
mania, and can further escalate into aggressive behavior and potentially lead to
injuries in patients and staff. Medications used to treat agitation include
antipsychotics and
benzodiazepines, usually administered intramuscularly when rapid action is desired.
Loxapine, a first-generation
antipsychotic, has recently been reformulated into an inhaled
powder that allows for direct administration to the lungs, resulting in rapid absorption into the systemic circulation. Administered via a single-use device, inhaled
loxapine was tested in randomized controlled trials in agitation associated with
schizophrenia or bipolar
mania; doses of 5 mg and 10 mg were found to be efficacious, with an apparent dose response. In the Phase III studies, number needed to treat versus placebo for a ≥40% reduction from baseline on the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC) at 2 hours was three for patients with
bipolar disorder, and five for 5 mg and four for 10 mg for patients with
schizophrenia, with effect sizes comparable to what has been observed in analogous studies of
intramuscular injection of
antipsychotics or
lorazepam. Separation from placebo on the PANSS-EC was as early as 10 minutes postinhalation, the first time point where this was measured.
Dysgeusia was the most commonly encountered spontaneously reported adverse event. Adverse events related to extrapyramidal symptoms and
akathisia were relatively rare. Spirometry studies identified the potential for
bronchospasm particularly in persons with
asthma. Because of concerns over pulmonary safety, inhaled
loxapine is restricted to use in hospitals and patients need to be prescreened for the presence of
pulmonary disease, as well as monitored for signs and symptoms of
bronchospasm for 1 hour postdose administration, as per a Food and Drug Administration-mandated Risk Evaluation and Mitigation Strategy.