Haloperidol for the treatment of nausea and vomiting in palliative care patients

Haloperidol is often used to help control nausea (feeling sick) or vomiting (being sick), both of which are common problems for patients with serious life-threatening illnesses. Haloperidol can be given by mouth or by injection. There has been some research looking at how this drug works in nausea and vomiting caused by surgery and when trying to prevent nausea and vomiting caused by anti-cancer treatments.

This is an update of the original review published in 2009 for which no studies met the inclusion criteria. For this update, in a search of the published literature in November 2014 we found one moderate quality randomised controlled trial which compared ABH (Ativan®, Benadryl®, Haldol®) gel, containing haloperidol and two other medications, to placebo.

The trial showed no difference between ABH gel and placebo. However it has previously been shown that haloperidol is not absorbed after applying ABH gel, so this result is not surprising. We identified a trial of haloperidol for nausea and vomiting in patients with cancer, with initial results presented at a conference. This suggests that haloperidol is effective in 65% of patients, but the results were not fully published at the time of our review. A further trial has opened in Australia, comparing haloperidol with another medication used for nausea, methotrimeprazine (levomepromazine).

Authors' conclusions: 

Since the last version of this review, we found one new study for inclusion but the conclusion remains unchanged. There is incomplete evidence from published RCTs to determine the effectiveness of haloperidol for nausea and vomiting in palliative care. Other than the trial of ABH gel vs placebo, we did not identify any fully published RCTs exploring the effectiveness of haloperidol for nausea and vomiting in palliative care patients for this update, but two trials are underway.

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Background: 

Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed to relieve these symptoms. This is an updated version of the original Cochrane review published in Issue 2, 2009, of Haloperidol for the treatment of nausea and vomiting in palliative care patients.

Objectives: 

To evaluate the efficacy and adverse events associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients.

Search strategy: 

For this updated review, we performed updated searches of CENTRAL, EMBASE and MEDLINE in November 2013 and in November 2014. We searched controlled trials registers in March 2015 to identify any ongoing or unpublished trials. We imposed no language restrictions. For the original review, we performed database searching in August 2007, including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. Handsearching complemented the electronic searches (using reference lists of included studies, relevant chapters and review articles) for the original review.

Selection criteria: 

We considered randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting, for inclusion. The studies had to be conducted with adults receiving palliative care or suffering from an incurable progressive medical condition. We excluded studies where nausea or vomiting, or both, were thought to be secondary to pregnancy or surgery.

Data collection and analysis: 

We imported records from each of the electronic databases into a bibliographic package and merged them into a core database where we inspected titles, keywords and abstracts for relevance. If it was not possible to accept or reject an abstract with certainty, we obtained the full text of the article for further evaluation. The two review authors independently assessed studies in accordance with the inclusion criteria. There were no differences in opinion between the authors with regard to the assessment of studies.

Main results: 

We considered 27 studies from the 2007 search. In this update we considered a further 38 studies from the 2013 search, and two in the 2014 search. We identified one RCT of moderate quality with low risk of bias overall which met the inclusion criteria for this update, comparing ABH (Ativan®, Benadryl®, Haldol®) gel, applied to the wrist, with placebo for the relief of nausea in 22 participants. ABH gel includes haloperidol as well as diphenhydramine and lorazepam. The gel was not significantly better than placebo in this small study; however haloperidol is reported not to be absorbed significantly when applied topically, therefore the trial does not address the issue of whether haloperidol is effective or well-tolerated when administered by other routes (e.g. by mouth, subcutaneously or intravenously). We identified one ongoing trial of haloperidol for the management of nausea and vomiting in patients with cancer, with initial results published in a conference abstract suggesting that haloperidol is effective for 65% of patients. The trial had not been fully published at the time of our review. A further trial has opened, comparing oral haloperidol with oral methotrimeprazine (levomepromazine) for patients with cancer and nausea unrelated to their treatment, which we aim to include in the next review update.