121 - Transdermal

Transdermal

Schizophrenia and related psychoses CHAPTER 1 ­haloperidol had a shorter time to peak levels (15 minutes) and a bioavailability comparable to oral routes of administration. Similar findings have been reported with droperidol.6 Intravenous Intravenous haloperidol is often used off-­label to manage acute behavioural disturbance or agitation and psychosis in patients with delirium in a general hospital setting. However, antipsychotics are probably not effective in delirium. A large clinical trial (n = 566) showed no evidence that either IV haloperidol or ziprasidone provided benefit over placebo in patients with delirium in intensive care.7 Other studies have reported similar findings.8 In respect to toxicity, a systematic review found that IV haloperidol did not cause greater QT prolongation than placebo, but close ECG monitoring is officially advised for IV haloperidol.9 Doses between 5 and 10mg are typically recommended but doses in the literature have ranged from 50 to 1500mg (over hours to days).9 A review of observational studies reported effectiveness of off-­label IV olanzapine.10 Bolus doses from 2.5 to 10mg (maximum dose of 30mg/day) have apparently been safely administered. IV droperidol is used off-­label to manage acute behavioural disturbance. Low-­ dose IV prochlorperazine (a piperazine phenothiazine)11 has been used in migraine.12 Sublingual Asenapine is the only commercially available antipsychotic designed for sublingual use. When used sublingually, the bioavailability of asenapine is 35%, compared with only 2% when taken orally.13 Other drugs may be absorbed sublingually but this has not been investigated. Dexmedetomidine is used sublingually in acute agitation.14,15 Buccal Buccally administered drugs are absorbed through the lining of the cheek. Compared with sublingual use, buccal administration results in somewhat slower absorption.13 There are no commercially available preparations licensed for buccal use and there has been little clinical investigation into this route of administration for antipsychotics. Prochlorperazine is available in the UK as a buccal tablet16 but it is indicated for the treatment of nausea and vomiting associated with migraines.17 Prochlorperazine is now rarely used for psychiatric indications and the dose needed for an antipsychotic effect (75–100mg a day) is much greater than that used for nausea. Transdermal Asenapine is available in the USA as a daily transdermal patch (Secuado) for treatment of adults with schizophrenia. Blonanserin (Lonasen) is commercially available as a daily transdermal patch in China, Japan and South Korea. Transdermal drug delivery minimises fluctuations in plasma drug concentrations and allows for lower doses (by bypassing first-­pass metabolism) and possibly reduced systemic adverse effects. At the time of writing, proof of concept clinical trials of once-­weekly aripiprazole transdermal patch had been successfully conducted.18 Chlorpromazine, haloperidol, olanzapine, prochlorperazine, quetiapine and risperidone have been developed as transdermal delivery systems but are not commercially available.19,20