<p>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</p>

Abstract

Agitation is a common and serious symptom of bipolar mania and schizophrenia, and can be defined as excessive motor and verbal activity. If left unrecognized and untreated, agitation can evolve into aggression, resulting in potential patient and staff injury. An ideal treatment for agitation would have a rapid onset, cause calmness without sedation, and be tolerable, efficacious, and non-coercive, while managing the underlying condition. A novel approach for the treatment of agitation is inhaled loxapine. Inhaled loxapine is rapidly absorbed into the systemic circulation through the alveoli, resulting in a near immediate onset of action. The efficacy of inhaled loxapine was established in an extensive clinical development program that included persons with schizophrenia and bipolar mania. Additionally, inhaled loxapine has comparable efficacy to intramuscular ziprasidone, olanzapine, haloperidol, aripiprazole, and lorazepam, with the added benefit of being non-painful and non-traumatizing. Inhaled loxapine carries a bolded black box warning for bronchospasm, and as a result, in the US, requires enrollment in a Risk Evaluation and Mitigation Strategy program, and is contraindicated in those with pulmonary disease. Additionally, the use of inhaled loxapine can be associated with dysgeusia and throat irritation. Inhaled loxapine requires some degree of patient cooperation, and therefore may not be appropriate for all agitated patients.

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder

“…7,21 Although the FDA has approved non-IM formulations of loxapine (inhaled) and dexmedetomidine (sublingual) for the treatment of agitation associated with schizophrenia or bipolar disorder, both must be administered under the supervision of a health care professional. 35,36 While IM formulations predominate in the treatment of acute agitation, unmet medical needs remain. In particular, there is a need for treatment options that can be used quickly in the community setting to help avoid progression to aggression.…”

“…Overall, inhaled loxapine is rapidly absorbed, with quick onset of action and comparable efficacy to IM ziprasidone, olanzapine, haloperidol, aripiprazole, and lorazepam, but can cause pulmonary adverse effects. 35 Clinical development of the formulation included a phase 2 trial and phase 3 trial in adult patients with schizophrenia and a phase 3 trial in adult patients with bipolar mania. 35 The 2 phase 3 randomized, double-blind, multisite, placebo-controlled, parallel-group trials each enrolled > 300 participants who received inhaled loxapine 5 mg, 10 mg, or placebo.…”

The Management of Psychomotor Agitation Associated with Schizophrenia or Bipolar Disorder: A Brief Review

“…In a majority of studies reporting safety outcomes in patients with schizophrenia or BD, inhaled loxapine was well tolerated and did not produce excessive sedation [ 53 , 54 , 55 ]. The most commonly reported adverse effects were mild to moderate and included dysgeusia, throat soreness, and sedation [ 50 , 51 , 52 , 56 ].…”

Agitation in schizophrenia: origins and evidence-based treatment

“…Inhaled loxapine remains available as a fast-acting intervention to manage agitation associated with schizophrenia, as reviewed in an article examining its safety, efficacy, and acceptability to patients [36 ▪ ]. This is not a new intervention, having been approved by the US FDA in 2012, but because of cost and restrictions on use due to a Risk Evaluation and Mitigation Strategy program focused on pulmonary monitoring, it has not been widely adopted.…”