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Loxapine: New Inhaled Antipsychotic Safe?

February 4, 2012 · Jim Amos

There’s a new rapidly acting formulation of the antipsychotic loxapine for the treatment of agitation in patients with bipolar disorder or schizophrenia. The patient self-administers the drug by inhaling it through a handheld device called a “Staccato” [1]. It can calm agitation in as little as 10 minutes, reportedly.

The Food and Drug Administration (FDA) advisory panel “narrowly recommended” approval of the drug provided a Risk Evaluation and Mitigation Strategy (REMS) proposed by the FDA be used and provided only one dose in 24 hours be administered.

There was opposition. Some members on the advisory panel had safety concerns about the risk for bronchospasm with the inhaled agent. Some patients with asthma or obstructive pulmonary disease had reductions in pulmonary function when treated with Loxapine. Under some circumstances, when it is challenging to get an accurate medical history from the patient or difficult to train an agitated patient how to use the inhaler device properly or to safely monitor them for respiratory-related adverse effects, the device could lead to pulmonary toxicity.

My major concern as a psychiatric consultant is the non-FDA approved or off-label use to which inhaled Loxapine might be put. I can see this happening with delirious patients misidentified as being “psychotic” or misdiagnosed with a primary psychiatric disorder in the emergency room or in the general hospital. Haldol and other antipsychotics were originally developed for those with schizophrenia and bipolar disorder. However, antipsychotics were quickly diverted for quelling agitation in delirious patients–some of them with the very kind of pulmonary diseases which Loxapine could exacerbate and which could lead to a vicious cycle of worsening medical illness and worsening delirium.

We could say that because the delirious patient is hospitalized, this would be the ideal place to use the inhaled antipsychotic because respiratory function can be closely monitored and problems like bronchospasm can be quickly dealt with.

Are all delirious patients in the hospital? No, many delirious patients are at home, nursing homes, or other long-term care facilities. Rarely, they’ll even be on general psychiatry units, the places where the capability of providing safe, effective, and timely emergency medical treatment can be near nonexistent. Even those with a clear psychiatric indication for the drug who are on inpatient psychiatric units who might benefit from the drug may not get it because of worry about the respiratory side effect.

I’m not saying there are no risks to using injectable antipsychotics to calm severe agitation, including cardiac arrhythmias–but do we need another agent carrying yet another risk for a medical complication?

In the end, a risk/benefit analysis must be done to determine if the potential risk of injury during a violent outburst from a psychotic (or delirious?) patient outweighs the risk  for respiratory problems due to inhaled Loxapine.

1. Mechcatie, E. (2012). FDA Panel Recommends Loxapine for Approval. Clinical Psychiatry News, IMNG Medical Media. 40.
If approved, the drug would be the first inhaled treatment for agitation in schizophrenia or bipolar.

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Posted In: Blogging, Delirium, Mental Health, Psychiatry, Psychosomatic Medicine
Tagged: inhalded antipsychotic, inhaled loxapine, loxapine, postaday, Staccato device

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