Haloperidol

Clinical question 2b:

What is the effect of haloperidol in the treatment of nausea and/or vomiting in patients in the palliative phase of cancer, heart failure, COPD, MS, ALS or renal failure?

Recommendation

Haloperidol is recommended for the treatment of nausea and vomiting in the palliative phase as an alternative for metoclopramide or domperidone, especially if there is another indication for this agent (such as hallucinations or (starting) delirium).

Introduction

Haloperidol is a butyrophenone derivate with a antipsychotic and a small sedating effect. It blocks both dopaminergic (D2) and alpha1-adrenergic receptors and presumably also the dopamine receptors in the chemoreceptor trigger zone. It has a strong central antidopaminergic and a weak central anticholinergic action.

Haloperidol is registered in the Netherlands as medication for nausea and vomiting (excluding vomiting due to travel sickness), if other agents fail or are contraindicated.

In the follwing text, the role of haloperidol in the prevention and treatment of nausea and vomiting as a result of chemotherapy will not be discussed.

Literature discussion

During the literature search, four systematic reviews [Critchley 2001; Davis 2010; Glare 2004; Perkins 2010], one study [Hardy 2010] and a protocol of the Cleveland Clinic [Gupta 2012] were found.
Critchley conducted a systematic review of the antiemetic effect of haloperidol, droperidol or butyrophenone in patients with an advanced stage of cancer [Critchley 2001]. Patients undergoing chemotherapy were excluded. Critchley found four case studies and two case reports. Critchley concluded that, based on this literature, a statement could not be made on the effect of haloperidol for nausea and vomiting in patients with an advanced stage of cancer [Critchley 2001].

Glare conducted a systematic review of the effect of antiemetics in patients with an advanced stage of cancer [Glare 2004]. Two systematic reviews, seven randomised controlled trials and twelve studies or case series were found. Glare concluded that haloperidol may be effective in the treatment of nausea with advanced cancer [Glare 2004].

Perkins conducted a systematic review of the antiemetic effect of haloperidol in the palliative care of patients with nausea and vomiting [Perkins 2010]. No randomised controlled trials or other articles were found that provided information on the effectiveness of haloperidol for nausea or vomiting in the palliative phase. Perkins concluded that there are no randomised studies that provide information on haloperidol as antiemetic in the palliative phase [Perkins 2010].

Davis conducted a systematic review of antiemetics in patients with an advances stage of cancer [Davis 2010]. He also did not find evidence for the effectiveness of haloperidol.

Hardy conducted a clinical study that included 42 patients with cancer who suffered from nausea and/or vomiting that was unrelated to chemotherapy [Hardy 2010]. Nausea and/or vomiting were both measured using a 0-4 point scale. Patients were treated with haloperidol at two dosage levels: 1) 1.5 orally once daily or 1.5 mg s.c./24 hours, or 2) 1.5 mg orally twice daily or 3 mg/24 hours. Patients were treated for five days. On day two, 33 patients were evaluable for response, on day 5 twenty-three patients. Responses on day two and five were seen in 61% and 74%, respectively, of all evaluable patients. If the non-evaluable patients were included, the response percentages were 47% and 40%, respectively. The researchers concluded that haloperidol has some effectiveness in the treatment of nausea and vomiting.

Gupta wrote "The Cleveland Clinic Protocol" for the treatment of patients with nausea and vomiting in the ‘Harry R Horvitz Center for Palliative Medicine' [Gupta 2012]. Gupta concluded that on the basis of practice-based medicine within the palliative expertise centre of the Cleveland Clinic, it is recommended to use haloperidol (1 mg orally twice daily or 5 mg/24 hours s.c. or i.v.) as second choice after metoclopramide.

There are indications that haloperidol is an effective antiemetic in patients with an advanced stage of cancer.
Hardy 2010

In daily practice, haloperidol is used often and with good effect in the treatment of nausea and vomiting.
Haloperidol has a more limited mode of action compared to metoclopramide and domperidone because it is only a dopamine-antagonist and not a prokinetic agent. It is not rational to use haloperidol in patients who do not respond sufficiently to metoclopramide or domperidone in adequate doses.

Haloperidol can be used for multiple symptoms in the terminal phase at the same time, such as confusion, which is common in the last week before death [Klinkenberg 2004].