Haloperidol

To determine the effects of treatments for nausea and vomiting either as a result of the disease or its treatment in adults with cancer and other chronic diseases

Databases reviewed searched were MEDLINE, Embase, and the Cochrane database. Harm alerts from the Food and Drug Administration (FDA) and the United Kingdom regulatory agency also were reviewed.

No separate description of the volume of literature evaluated or the specific evaluation process was provided. The Grading of Recommendations Assessment, Development and Evaluation (GRADES) system was used for rating the evidence, and these results were provided. The literature review was completed as of April 2008.

The study reported on 13 randomized, controlled trials (RCTs), representing more than 14,000 patients with cancer. These included studies of nausea and vomiting as a result of disease or treatment.

Results indicated that 5-HT₃ RAs + dexamethasone was beneficial.

The following were identified as likely to be beneficial.

• 5-HT₃ RAs + corticosteroid with radiotherapy-induced nausea and vomiting
• Aprepitant added to conventional regimens
• Haloperidol
• Metoclopramide for chemotherapy-induced nausea and vomiting (CINV)
• Phenothiazines
• Venting gastrostomies

Cannabinoids were identified as being a tradeoff between benefit and harm.

The following were determined to have unknown effectiveness.

• 5-HT₃ receptor antagonists (RAs) for radiation-induced nausea and vomiting
• Antihistamines
• Antimuscarinics
• Antipsychotics
• Benzodiazepines for CINV

• Although no evidence was identified, and, at this writing, there was a stated drug safety alert on haloperidol, this review identified haloperidol as likely to be beneficial. It is unclear how this can meet this category.
• Results cited tended to focus on vomiting episodes and did not address the symptom of nausea.
• Results were a mix of symptoms from the disease itself or treatment, so differentiation of applicability was not always clear.
• Some aspects of the search strategy were unclear.
• Some interventions stated that no RCTs or systematic reviews were found, so no evidence was provided; however, in other areas, observational studies and consensus opinions were cited as supporting evidence.
• Inclusion and exclusions were not stated.
• No information was included on nonpharmacologic interventions in combination with antiemetic regimens.

To evaluate the efficacy of a topical gel containing lorazepam, diphenhydramine, and haloperidol (ABH), in reducing chemotherapy-induced nausea and vomiting (CINV) among patients with cancer

This article reported on two pilot trials.

Patients in one physician practice were prescribed prophylactic antiemetics according to standard guidelines. They were given a prescription for six prefilled, capped tuberculin syringes of ABH gel when they received emetogenic chemotherapy. The patients were instructed to use the ABH gel when they developed significant nausea or vomiting in the days that followed chemotherapy, with the option to repeat use at six-hour intervals. Patients were instructed to place 0.5 ml of the gel on the palmar aspects of their wrists using the prefilled syringe. After applying the gel, the participants were instructed to rub their wrists together gently for one to three minutes to facilitate transdermal absorption.

In the first trial, an investigator contacted patients by telephone within one month. Patients provided verbal informed consent at this time. The investigator asked patients questions about their progress with ABH gels using a standard questionnaire, developed for the pilot. Patients were asked to rate their CINV and if they believed the gel to cause sedation, skin irritation, or muscle spasms.

In the second trial, after patients provided verbal consent, an investigator used a structured interview by telephone or in person to rate the severity of CINV on a combined scale at 30 minutes and fours hours after applying the ABH gel.

• Trial 1 consisted of 23 adult patients with solid tumor or hematology cancer diagnosis receiving chemotherapy.
• Trial 2 consisted of 10 adult patients with a cancer diagnosis.
• No control for diagnosis or chemotherapy treatment was included.

The trials were conducted at the outpatient clinic of a university in the midwestern United States.

• Trial 1 incorporated the use of a standardized questionnaire developed for the study.
• Trial 2 involved the use of a numeric rating scale, ranging from 0 (no nausea or vomiting) to 10 (worst imaginable nausea or vomiting).

• In trial 1, 74% of patients believed the gel decreased their nausea and 70% of patients experienced relief from vomiting. The majority of patients (70%) reported relief within 30 minutes of applying the gel. Some of the patients (13%) reported fatigue after using the gel. No patients reported skin irritation or muscle spasms.
• In trial 2, nausea scores significantly decreased at 30 minutes. No significant side effects were reported.

Transdermal ABH gel decreased the severity of CINV with only slight sedation reported.

• The sample size was small and heterogeneous.
• No control for disease, chemotherapy agents, cycle, or antiemetic agents was included.
• Trial 1 was retrospective, asking participants to recall symptom experience.

Use of transdermal ABH is convenient and easily taught to patients; however, availability of this combination topical agent may be a challenge in community settings because hospital pharmacies are less likely to compound products.

The objective of the guidelines is to provide palliative care practice guidelines for patients with cancer, facilitating the appropriate integration of palliative care into oncology practice.

These are consensus-based guidelines.

Included in the guidelines are multiple phases of care with palliative care applications. 

The NCCN made recommendations on the following symptoms.

Anorexia
Nutritional support, including enteral and parenteral feeding, should be considered. Appetite stimulants such as megestrol acetate and corticosteroids can be used when appetite is an important aspect of quality of life.

Chemotherapy-Induced Nausea and Vomiting (CINV)
Recommendations include prochlorperazine, haloperidol, metoclopramide, or benzodiazepines. Adding 5-HT₃ receptor agonists, anticholinergics, antihistamines, corticosteroids, antipsychotics, and cannabinoids also can be considered. Palliative sedation can be considered as a last resort.

Constipation
Increase fluid intake, dietary fiber, and physical activity. Opioid-induced constipation should be anticipated and treated prophylactically with laxatives.

Dyspnea
Pharmacologic interventions include opioids or benzodiazapines. Scopolamine, atropine hyoscyamine, and glycopyrrolate are options to reduce excessive secretions.

Pain
Do not reduce opioid dose for symptoms such as decreased blood pressure or respiratory rate. Palliative sedation can be considered for refractory pain.

Sleep/Wake Disturbances
For refractory insomnia with no underlying physiologic cause, pharmacologic management includes diazepam, zolpidem, and sedating antidepressants. Cognitive behavioral therapy may be effective. If present, restless leg syndrome can be treated with ropinirole.

• Recommendations are predominantly consensus- rather than evidence-based. 
• Recommendations are generally based on low-level evidence. 
• Recommendations regarding CINV seem particularly out of date and are not in concert with current evidence.

Recommendations provide expert opinion/consensus-level suggestions for management of various symptoms. Many recommendations, such as those for CINV, do not agree with current evidence in these areas.