Is inhalation antipsychotic safe and useful? Annals Gen psych. 2015.April.

 12.06.2015

Controlling acute agitation early on is important to avoid serious and harmful consequences. Oral and IM medications are the main pharmacological routes available now to achieve this. Inhalation route is another possibility opened with the licensing of the first inhalation antipsychotic medication.

Loxapine is a typical antipsychotic in use since 1970’s. It is  widely used in France and Canada. Inhalation form is approved  ( US & EU) for acute treatment of agitation in adults with schizophrenia / bipolar disorder. Maximum plasma concentration is achieved in approximately 2 minutes. Half-life for the 5- and 10-mg doses is approximately 6 hours.

Dina Popovic, Philippe Nuss and Eduard Vieta review efficacy and safety of  loxapine in this article.

Loxapine is structurally similar to clozapine. It has actions on D2 as well as 5 HT 2A receptors. It has atypical characteristics. A 2007 Cochrane review showed that loxapine  ( oral) is as effective as other typical and atypical antipsychotics. As expected,  EPS is the main side effect of medications like loxapine. There have been no trials assessing the efficacy of the oral or intramuscular formulation of loxapine in acute treatment of manic episode, but is still widely prescribed in the treatment of mania.

Effect on  acute agitation ( inhalation loxapine)

In two phase III studies (one in subjects with schizophrenia, the other in subjects with bipolar disorder) inhaled loxapine doses of 5 and 10 mg were both superior to placebo 10 min after administration. Pooled data suggest  that NNT  is  comparable to that observed for intramuscular administration of other antipsychotics.

Interestingly,  no clinically relevant extrapyramidal side effects or akathisia have emerged following administration of loxapine 10 mg or 5 mg. There is no apparent QT prolongation . Most common adverse event was short-term dysgeusia.

 Active airways disease (asthma and chronic obstructive pulmonary disease)  is a contraindication due to the risk of bronchospasm .

Limitations:  Data sets available are small .  The inhaler is single use only . The recommended use of  10 mg administration ( only a single dose  in 24 hrs) raises the issue of further medication choices if agitation is not controlled. Screening for chest conditions  ( including auscultation ) may be difficult when patients are agitated. 

Comments: If  the favourable side effects profile is established in large data sets, loxapine inhalation may be a preferred  option in early stages of agitation in cooperative patients.  This is particularly the case as ECG is  recommended/ required before administering  haloperidol, which is   commonly used to control agitation.

 Summary of the article:

Revisiting loxapine: a systematic review. Popovic D, Nuss P, Vieta E. Ann Gen Psychiatry. 2015 Apr 1;14:15. doi: 10.1186/s12991-015-0053-3

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